bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of P2X receptors on rat microglial cells during early development
Authors: Xiang Zhenghua , Burnstock Geoffrey
Published: May 2005

We have used single‐ and double‐labeling immunfluorescence and reverse transcription‐polymerase chain reaction (RT‐PCR) methods to examine expression of P2X receptor subtypes on microglial cells of brain in late embryonic and postnatal rat, in the N9 microglial cell line and primary cultured microglial cells. P2X1, P2X4, and P2X7 receptors were shown on microglial cells from late embryonic day 16. Almost all the microglial cells that were positive for the marker ED1, expressed P2X1 and P2X4 receptors, whereas only about 30% of the cells with ED1‐immunoreactivity were found to express the P2X7 receptor. Positive cells were localized mainly in the white matter and around ventricles. From postnatal day 7, many microglial cells with P2X4 receptor‐immunoreactivity were seen around the blood vessels. At postnatal day 30, microglial cells with P2X1 receptor‐immunoreactivity disappeared and the cells with P2X4 receptor‐immunoreactivity were mainly localized around blood vessels and lining the subarachnoid space. From postnatal day 30, the microglial cells with P2X7 receptor‐immunoreactivity were found to be distributed widely in the forebrain. Cells with P2X7 receptor‐immunoreactivity from P30 were not labeled by ED1, but some were labeled by isolectin B4. The expression of P2X1, P2X4, and P2X7 receptor mRNA and protein on primary cultures of rat microglial cells and on the N9 microglial cell line was demonstrated with immunocytochemistry and RT‐PCR. This is the first report that the P2X1 receptor is expressed on microglial cells, at least in early development, before postnatal day 30. © 2005 Wiley‐Liss, Inc.
Effect of anandamide uptake inhibition in the production of nitric oxide and in the release of cytokines in astrocyte cultures
Authors: Ortega‐Gutiérrez Silvia , Molina‐Holgado Eduardo , Guaza Carmen
Published: May 2005

Astrocytes play a key role regulating aspects of inflammation in the central nervous system (CNS). Several enzymes, such as the inducible nitric oxide synthase (iNOS) or the cyclooxygenase‐2 (COX‐2), along with different inflammatory mediators such as the free radical nitric oxide (NO) or proinflammatory cytokines, have been proposed to be involved in the cell damage associated with neuroinflammation. Recent studies suggest that the endogenous cannabinoid system (ECS) may be involved in the regulation of neuroinflammation. Cannabinoid agonists decrease neurotoxicity and release of proinflammatory factors from activated glial cells and anandamide itself is able to promote antiinflammatory responses in astrocytes via CB1 cannabinoid receptors. The present study is aimed at studying whether UCM707, a potent and selective anandamide uptake inhibitor, is able to inhibit the production of proinflammatory mediators by LPS‐stimulated astrocytes. Our findings indicate that UCM707 is able to reduce NO release, iNOS expression, and the production of the proinflammatory cytokines tumoral necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in a significant manner, while producing a slight increase in IL‐6 levels. These effects can be reproduced by administration of the synthetic agonist HU210 and partially or totally blocked by administration of CB1 or CB2 selective antagonists, further supporting the involvement of the ECS. These results confirm the ability of UCM707 to reinforce the beneficial effects induced by anandamide and make it an attractive candidate for the management of those pathologies with neuroinflammation as one of their hallmarks. © 2005 Wiley‐Liss, Inc.
Interferon‐γ inhibits cell cycle exit in differentiating oligodendrocyte progenitor cells
Authors: Chew Li‐Jin , King William C. , Kennedy Ann , Gallo Vittorio
Published: May 2005

The developmental processes of the oligodendrocyte progenitor cell (OPC) lineage that are targeted by interferon‐γ (IFN‐γ) were studied in primary rat OPC cultures. Under conditions of thyroid hormone‐mediated oligodendrocyte differentiation, IFN‐γ produced a dose‐dependent apoptotic response in OPCs. The lowest dose tested (15 ng/ml or 75 U/ml) was nonapoptotic, but activated detectable STAT1 DNA‐binding. At this dose, IFN‐γ reduced the percentage of mature O1+ cells and increased the percentage of immature A2B5+ OPCs. This was observed without significant change in total cell number and cytotoxicity, and was accompanied by an increase in BrdU‐labeled A2B5+ and O4+ cells. FACS analysis confirmed a lack of apoptotic sub‐G1 cells and revealed a greater percentage of S‐ and G2/M‐phase OPCs with IFN‐γ treatment. Dual immunostaining with Ki‐67 and Olig2 showed a smaller percentage of Olig2+ cells in G0 phase in IFN‐γ‐treated OPCs, indicating loss of G1 control. Instead, increased levels and phosphorylation of the checkpoint protein p34cdc2 by IFN‐ suggested increased partial arrest in G2. IFN‐γ not only sustained expression of PCNA and the G1‐S regulators retinoblastoma protein, cyclin D1, cyclin E, and cdk2, but also decreased p27 levels. In addition to changes in cell proliferation and differentiation, IFN‐γ attenuated myelin basic protein (MBP) expression significantly, which was associated with decreased expression of both MBP and Sox10 RNAs. These findings indicate that IFN‐γ not only maintains cell cycle activity that could predispose OPCs to apoptosis, but also overrides G1–G0 signals leading to thyroid hormone‐mediated terminal differentiation and myelin gene expression. © 2005 Wiley‐Liss, Inc.
Effects of cholinesterase inhibitors appear greater in patients on established antihypertensive therapy
Authors: Rozzini Luca , Vicini Chilovi Barbara , Bellelli Giuseppe , Bertoletti Erik , Trabucchi Marco , Padovani Alessandro
Published: May 2005

Introduction

There is increasing evidence that hypertension may contribute to development of dementia. Studies show that blood pressure lowering therapy might protect against cognitive deterioration and that antihypertensive treatment reduce the incidence of dementia.

Aim

We hypothesize that administration of cholinesterase inhibitors (AChEis) to patients with Alzheimer's Disease (AD) receiving antihypertensive medications therapy would result in clinical benefits for a period of 40 weeks in routine clinical practice.

Methods and materials

Patients with possible or probable AD were enrolled from 16 Alzheimer evaluation units (UVA) of Brescia and Cremona (Northern Italy). Patients treated with donepezil, rivastigmine and galantamine for 40 weeks independently of dosages were selected. Patients were evaluated at baseline (T0), 4 weeks (T1), 16 weeks (T2) and 40 weeks (T3).

Results

416 patients completed the study at 40 weeks; of these 255 were ‘non users’ while 161 utilized antihypertensive drugs (‘users’). The mean change in MMSE score from baseline to week 40 demonstrate that antihypertensive‐treated patients improved by 0.7 points while patients receiving only AChEis remain stables. Analyzing separately patients (n = 183) that ameliorate (responders) on cognition at T3 ( ≥ 1 point MMSE score increase) a significant differences in favor of ‘users’ antihypertensive drugs over ‘non users’ on cognition at weeks 16 and 40 has been demonstrated. In particular, at T2 the mean change of MMSE from baseline in ‘users’ was 3.2 ± 2.6 vs ‘non users’ 2.2 ± 2.3 ( p = 0.016) and at T3 was 3.5 ± 2.5 vs ‘non users’ 2.0.2.7±1.6 ( p = 0.018). Antihypertensive drugs were independently associated with cognitive improvement in responder patients treated with AChEis (95% CI: 0.41–1.79; p = 0.002).

Conclusion

Antihypertensive medications in AD patients treated with AChEis are associated with an independent improvement on cognition after 40 weeks of treatment. Copyright © 2005 John Wiley & Sons, Ltd.
Correlates of cognitive impairment and depressive symptoms among older adults in Korea and Japan
Authors: Lee Yunhwan , Shinkai Shoji
Published: May 2005

Background

Cognitive impairment and depressive symptoms impose a heavy burden on the care of the elderly in Japan and Korea, two of the fastest aging nations in Asia. The purpose of this study was to examine and compare factors associated with cognitive impairment and depressive symptoms among older persons in the two countries.

Methods

In 2002, representative samples of community‐dwelling people aged 65 and older were selected among residents in Anyang, Korea and Yoita, Japan. Mini‐Mental State Examination and Geriatric Depression Scale were used to assess the elderly's mental status. Sociodemographics, physical function, chronic conditions, social support, and health behaviors were examined to identify significant associations.

Results

The prevalence of cognitive impairment in older adults was 17.0% in Anyang and 14.6% in Yoita. The rates for depressive symptoms were 15.2% and 19.8%, respectively. Overall, functional capacity was the universal factor significantly associated with mental conditions. Self‐rated health and social support were also found to be independently associated with depressive symptoms in the study subjects. Differences in the patterns of association by community, however, were notable for other characteristics. For example, in factors associated with cognitive impairment, sociodemographic factors such as age, gender, and education were significant among Koreans, whereas socio‐behavioral factors such as obesity, social support and hospitalization experience were found to be significant for older Japanese residents.

Conclusions

Similarities in the patterns of association indicate the need for joint explorations into the role these factors play in affecting the mental health of older persons. Socioeconomic and regional differentials, however, may account for the disparity in the associations observed, suggesting the importance of developing mental health programs sensitive to the older individual's culture. Copyright © 2005 John Wiley & Sons, Ltd.
The course of neuropsychiatric symptoms in dementia. Part I: findings from the two‐year longitudinal Maasbed study
Authors: Aalten Pauline , de Vugt Marjolein E. , Jaspers Niek , Jolles Jaspers , Verhey Frans R. J.
Published: May 2005

Background

Although neuropsychiatric symptoms in dementia are common, there have been few large long‐term prospective studies assessing the course of a broad range of neuropsychiatric symptoms in dementia.

Objectives

To investigate the course of neuropsychiatric symptoms in patients with dementia, including data about prevalence, incidence and persistence.

Methods

One hundred and ninety‐nine patients with dementia were assessed every six months for two‐years, using the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms.

Results

Nearly all patients (95%) developed one or more neuropsychiatric symptoms in the two‐year study period. Mood disorders were the most common problem. The severity of depression decreased, whereas the severity of apathy and aberrant motor behaviour increased during follow‐up. The cumulative incidence was highest for hyperactive behaviours and apathy. Overall behavioral problems were relatively persistent, but most symptoms were intermittent, with apathy and aberrant motor behaviour being persistent for longer consecutive periods.

Conclusions

Neuropsychiatric symptoms in dementia are a common and major problem. Different symptoms have their own specific course, most of the time show a intermittent course, but behavioural problems overall are chronically present. The data have implications for developing treatment strategies. Copyright © 2005 John Wiley & Sons, Ltd.
The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub‐syndromes and the influence of clinical variables
Authors: Aalten Pauline , de Vugt Marjolein E. , Jaspers Niek , Jolles Jellemer , Verhey Frans R. J.
Published: May 2005

Background

Although several studies have mentioned associations between neuropsychiatric symptoms, there have been no prospective studies determining interrelations among behavioural sub‐syndromes.

Objectives

To investigate the influence of several clinical variables on the course of neuropsychiatric symptoms, and to determine interrelationships between the behavioural sub‐syndromes.

Methods

One hundred and ninety‐nine patients with dementia were assessed every six months for two‐years, using the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms.

Results

Age, sex, and socioeconomic status were not associated with a specific neuropsychiatric symptom. Greater cognitive impairment was related to more severe psychosis, and dementia stage influenced the course of total NPI problems. There were strong interrelations among most behavioural sub‐syndromes. The sub‐syndrome hyperactivity was of influence on the development of psychosis, but not vice versa. Neither was the sub‐syndrome mood/apathy of influence on the course of psychosis.

Conclusions

While different neuropsychiatric symptoms have their own specific correlates, there is a strong interrelationship between behavioural sub‐syndromes. The data have implications for clinicians and the nosology of neuropsychiatric symptoms in dementia. Copyright © 2005 John Wiley & Sons, Ltd.
Effects of a health advocacy, counselling, and activation programme on depressive symptoms in older coronary heart disease patients
Authors: Salminen Marika , Isoaho Raimo , Vahlberg Tero , Ojanlatva Ansa , Kivelä Sirkka‐Liisa
Published: May 2005

Objectives

To describe the effects of a health advocacy, counselling, and activation programme on depressive symptoms among older coronary heart disease (CHD) patients.

Methods

A randomised, controlled intervention study in Lieto, South‐western Finland. Older (65 years and older) patients with CHD were randomly divided into an intervention group (IG) (n = 116) and a control group (CG) (n = 106). Outcome measures comprised changes in depressive symptoms (Zung Self‐rating Depression Scale, ZSDS).

Results

Depressive symptoms tended to decrease in IG and to increase in CG among men scoring 45 ZSDS sum points or more at baseline. The differences of the changes between IG and CG were significant in favour of IG. No similar changes were found among women.

Conclusions

A health advocacy, counselling, and activation programme aimed to increase knowledge about CHD, social activities, contacts, roles, support, and exercising was effective in reducing depressive symptoms among male CHD patients suffering from a moderate or high amount of depressive symptoms. Copyright © 2005 John Wiley & Sons, Ltd.
Prevalence of depression among elderly Chinese with diabetes
Authors: Chou Kee‐Lee , Chi Iris
Published: May 2005

Background

To examine the association between diabetes and depression among older Chinese and to determine the extent to which depression is mediated by physical disability and diabetes‐related comorbid conditions.

Method

Cross‐sectional analysis of data from a population‐based study composed of a representative sample of 2003 non‐institutionalized older adults aged 60 and older living in Hong Kong who agreed to participate in the study. We examined the relation between diabetes and depression (measured with the Geriatric Depression Scale).

Result

12% of the older adults reported physician‐diagnosed diabetes and amongst these older persons with diabetes, 26% of them reported elated level of depressive symptoms. Logistic regression analyses revealed that diabetes was significantly related to depression even when controlling for age, gender, marital status, and education. More importantly, adjusted for self‐reported disability in three domains including self‐care, mobility, and higher functioning did not attenuate this association but the association disappeared after we adjusted for four diabetes‐related complications including heart disease, high blood pressure, stroke, and vision problems.

Conclusion

Diabetes is associated with depression and this association appears to be mediated by prevalent diabetes complications. This is of particular clinical important because although depression is often overlooked in the aged population, effective treatment is available and can result in improved medical outcomes. Copyright © 2005 John Wiley & Sons, Ltd.
The effect of staff training on the use of restraint in dementia: a single‐blind randomised controlled trial
Authors: Testad I. , Aasland A. M. , Aarsland D.
Published: May 2005

Background

Use of restraint amongst institutionalised elderly with dementia and problem behaviour not only remains widespread, but also appears to be accepted as inevitable.

Objective

The aim of this study was to reduce problem behaviour and the use of restraint in demented patients using a staff training program as intervention.

Methods

The study was a randomised single‐blind controlled trial and took place in Stavanger, Norway. Four nursing homes were randomised to a control or an intervention group after stratification for size. The intervention consisted of a full day seminar, followed by a one‐hour session of guidance per month over six months. The content of the educational program focused on the decision making process in the use of restraint and alternatives to restraint consistent with professional practice and quality care. The primary outcome measures were number of restraints per patient in the nursing homes in one week and agitation as measured with the Brief Agitation Rating Scale (BARS). These were rated before and immediately after the intervention was completed. The assessments were performed blind to design and randomisation group.

Results

Clinical and demographic variables did not differ between the intervention and control groups at baseline. After the intervention period, the number of restraints had declined by 54% in the treatment group, and increased by 18% in the control group. The difference between the two groups was statistically significant ( p = 0.013). There was a trend towards higher BARS score in the intervention compared to the control group at follow up ( p = 0.052).

Conclusion

Although the level of agitated behaviour remained unchanged or increased slightly, the educational program led to a significant reduction of the use of restraint in institutionalised elderly with dementia. These results suggest that educational programs can improve the quality of care of people with dementia. Copyright © 2005 John Wiley & Sons, Ltd.
The Extent of Liver Steatosis in Chronic Hepatitis C Virus Infection Is Mirrored by Caspase Activity in Serum *
Authors: Seidel Nicole , Volkmann Xandra , Länger Florian , Flemming Peer , Manns Michael P. , Schulze-Osthoff Klaus , Bantel Heike
Published: May 2005

Hepatic steatosis is a frequent histological alteration in chronic hepatitis C virus (HCV) infection that sensitizes the liver to cell injury, inflammation, and fibrosis via unclear mechanisms. Although apoptosis has been implicated in various liver diseases, its importance in HCV-associated steatosis is largely unknown. In this study, we investigated the role of caspases, the key regulators of apoptosis, and employed two novel caspase assays, an immunological and a luminometric enzyme test, to detect hepatic caspase activation in sera from HCV patients with different grades of steatosis. Our data show that increased caspase activation can be found not only in liver biopsies, but also in sera from HCV patients with liver steatosis. Patients with steatosis exhibited significantly higher serum levels of caspase activity compared with normal healthy individuals. Moreover, the extent of steatosis closely correlated with serum caspase activity, whereas in particular in cases of low or moderate steatosis, no correlation was found with aminotransferase levels.
In conclusion
, apoptotic caspase activation is considerably elevated in HCV-associated steatosis. More importantly, our data imply that measurement of caspase activation might be a sensitive serum biomarker to detect liver steatosis in patients with chronic HCV infection and other liver diseases. (Hepatology 2005.)
Locale and taxon systems: No place for neophrenology?
Authors: Whishaw Ian Q.
Published: May 2005

Cognitive mapping theory has had success in directing attention toward the role that the hippocampus plays in spatial navigation. Nevertheless, this critique argues that (1) the hip‐pocampus does play a relatively direct role in movement control: (2) an associationistic explanation more parsimoniously accounts for spatial navigation performance of rats than cognitive mapping theory; and (3) cognitive mapping theory is unnecessary psychological construct. Speculatively, it might be worthwhile considering that the explicit feature of human memory and voluntary movements in animals are ho mologous. Such a notion would lead to more emphasis on the analysis of the role that the hippocampus plays in the control of movement and less on its putative role in housing psychological constructs.
A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission
Authors: Terrian David M. , Ways D. Kirk , Gannon Robert L.
Published: May 2005

It has been suggested that the maintenance of long‐term potentiation (LTP) in the hippocampal mossy fiber (MF) synapse involves a presynaptic mechanism that does not require the activation of protein kinase C (PKC), since this enzyme appears to be absent in the MF presynaptic terminals. In the present study the authors evaluated this proposal by directly comparing the metabolic properties of hippocampal MF synaptosomes and a conventional P2B synaptosomes preparation prepared from the same hippocampal tissue. Protein kinase C‐dependent histone phosphotransferase activity was found to be comparable in MF and P2B synaptosomes. Western blot analysis was performed using antisera prepared against four of the PKC isoforms, and the results demonstrate that the α, β, and γ PKC isoforms are present in relatively equivalent amounts in these two subcellular fractions. However, the cytosolic fraction derived from the hippocampal MF synaptosomes appeared to contain a greater amount of the PKC−∈ isoform when compared to the P2B synaptosomal preparation. Four distinct endogenous substrates present in the MF synaptosomes are shown to be phosphorylated in response to PKC activation. A functional role for PKC in the hippocampal MF nerve endings seems to be indicated by the finding that 4β‐phorbol 12, 13‐dibutyrate (PDBu) and 4β‐phorbol 12, 13‐diacetate produce a dosedependent potentiation of the K+‐evoked release of endogenous glutamate and dynorphin B, while the inactive 4‐α‐phorbol was without effect. The PDBu‐induced enhancement of transmitter release was blocked by the PKC inhibitor, staurosporine. In addition, PDBu significantly facilitated the rise in cytosolic free calcium that immediately followed depolarization of the MF synaptosomal membrane. It is concluded that hippocampal MF presynaptic terminals possess a variety of PKC isoforms and that their activation may have an important facilitory influence on MF synaptic transmission and plasticity.
Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse
Authors: Schöpke R. , Wolfer D. P. , Lipp H.‐P. , Leisinger‐Trigona M.‐C.
Published: May 2005

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP–MF) at the midsepto‐temporal level correlates negatively with two‐way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP–MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP–MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2).

In 19 random‐bred mice (9 male, 10 female), the extent of the IIP–MF showed negative correlations with swimming time after platform reversal (day 4: r = −0.50, P<.03; day 5: r = −0.73, P>.001), but none during acquisition of the task. In addition, statstical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1–3, and a significantly faster swimming time in the strain C57 BL/6 (with large IIP–MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP–MF in both strains. Finally, variations of the IIP–MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP–MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.
Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits
Authors: Zhang Wan‐Qin , Mundy William R. , Thai Linda , Hudson Pearlie M. , Gallagher Michela , Tilson Hugh A. , Hong J. S.
Published: May 2005

The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer‐344 rats. Young adult (4‐month‐old) and aged (24‐month‐old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25–35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1–8)‐like immunoreactivity [DYN‐A(1–8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN‐A(1–8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.
The role of the perforant pathway as a trophic factor for neurotransmission in the rat dentate gyrus
Authors: Bekenstein Jonathan W. , Lothman Eric W.
Published: May 2005

Changes in electrophysiological function in the hilar associational pathway terminating on dentate granule cells in the rat hippocampal formation were studied following unilateral entorhinal cortex lesions. In rats lesioned as pups (postnatal day 4 [PN 4]) or as adults (PN 60) there was a profound loss of paired‐pulse inhibition at 30 days postlesion. Inhibition was unaffected at 10 days postlesion. Entorhinal cortex lesions did not affect population spike amplitude, population excitatory postsynaptic potentials slopes, or long‐term potentiation compared to the unlesioned hemisphere. The presence of a complete hippocampal commissurotomy had no effect on excitatory or inhibitory parameters. Laminar analyses of extracellular field potentials from animals lesioned as adults revealed an expansion of functional synapses outward into the dentate molecular layer. This expansion was complete by 10 postlesion days. The changes observed with laminar analyses were not contemporaneous with the changes in paired‐pulse inhibition. The loss of inhibition in the hilar associational pathway of entorhinal cortex‐lesioned animals thus implies a change in local circuit function rather than an effect from sprouted associational fibers directly onto granule cells. The lack of inhibition in the associational pathway in lesioned animals was not due to a failure of local circuit inhibitory function to develop, since the same findings were obtained when lesions were made neonatally or as adults. Rather, the authors suggest that the present findings arise because of the formation of functional, recurrent, excitatory mossy fiber collateral synapses following entorhinal cortex lesions.
Comparison of the effects of ethanol and chlordiazepoxide on electrophysiological activity in the fascia dentata and hippocampus regio superior
Authors: Steffensen Scott C. , Henriksen Steven J.
Published: May 2005

Acute intoxicating doses of ethanol‐producing blood alcohol levels of 120–200 mg% increase paired‐pulse (PP) inhibition in the dentate gyrus of anesthetized rats suggesting that ethanol increases recurrent inhibitory processes (Wiesner, J. B., and S. J. Henriksen (1987) Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus. Neurosci. Lett. 79:169–173). To further understanding of the neuronal mechanisms underlying this phenomenon, the authors studied the effects of the benzodiazepine (BZ), chlordiazepoxide, and acute intoxicating levels of ethanol on extracellular field potential recordings and single‐unit activity in the dentate gyrus and area CA1 of the hippocampus. In the dentate, ethanol had no effect on population excitatory postsynaptic potential (pEPSP) amplitudes or slopes; decreased population spike (PS) amplitudes (25%); increased PP inhibition; decreased dentate granule cell (DGC) spontaneous activity (58%); had no effect on putative interneuron spontaneous activity; and markedly increased post field potential‐evoked interneuron discharges (IDs, 218%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; increased PP inhibition; decreased DGC (62%) and interneuron (72%) spontaneous activity; and markedly decreased IDs (89%). In CA1, ethanol had no effect on pEPSP amplitudes or slopes; decreased PS amplitudes (26%); had no effect on PP responses; decreased pyramidal cell (PC) spontaneous activity (39%); had no effect on interneuron spontaneous activity; and markedly increased IDs (97%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; had no effect on PP responses; decreased PC spontaneous activity (41%); and had no effect on interneuron spontaneous activity or IDs. The results suggest that the BZs decrease principal cell excitability by postsynaptic facilitation of inhibitory processes, whereas ethanol decreases principal cell excitability by postsynaptic facilitation of inhibitory processes, whereas ethanol decreases principal cell excitability indirectly by increasing the excitability of inhibitory interneurons.
Modulation of high‐threshold Ca current and spontaneous postsynaptic transient currents by phorbol 12, 13‐diacetate, 1‐(5‐isoquinolinesulfonyl)‐2‐methyl piperazine (H‐7), and monosialoganglioside (GM1) in CA1 pyramidal neurons of rat hippocampus in vitro
Authors: Agopyan N. , Miu P. , Krnjević K.
Published: May 2005

Phorbol esters, which activate protein kinase C (PKC), enhance synaptic transmission in the CA1 subfield of hippocampus, both in situ and in vitro. The increase in synaptic transmission could be the consequence of enhanced Ca influx into nerve terminals, and perhaps a more general increase in voltage‐dependent Ca currents. The effects of phorbol 12, 13‐diacetate (PDAc) on the high‐voltage activated (HVA) Ca currents, as well as spontaneous transient currents were therefore investigated by intracellular recording in hippocampal slices. PDAc selectively augmented, by 45% ± 10%, the early peak of the HVA Ca current (but not its sustained component), and also spontaneous inhibitory postsynaptic currents. The inactive phorbol ester, 4 α‐PDAc, had no comparable effects. The actions of PDAc were reversible on prolonged washing, and they were antagonized by the PKC inhibitors (1‐(5‐isoquinolinesulfonyl)‐2‐methyl) piperazine (H‐7) and monosialoganglioside (GM1). In addition, GM1, which also activates the Ca/calmodulin‐dependent kinase, enhanced spontaneous excitatory postsynaptic currents, while inhibiting the IPSCs. It is concluded that activation of PKC increases HVA (probably N‐type) Ca current and facilitates ongoing GABAergic IPSCs.
Accumulation of glutamate is regulated by calcium and protein kinase C in rat hippocampal slices exposed to ischemic states
Authors: Lu Y. Ming , Lu B. Feng , Zhao F. Qing , Yan Y. Lan , Ho X. Pin
Published: May 2005

There is now convincing evidence that excessive accumulation of the excitatory amino acid glutamate (Glu) in the extracellular space is toxic to neurons. However, the regulation of the release and uptake of Glu in producing this toxic concentration has not been adequately ascertained. The authors report that in hippocampal slices, the output of Glu significantly increased under in vitro ischemic states. Glu in the extracellular space increased fivefold. Since daurisoline, a drug that blocks N‐type Ca2+ channels, or Ca2+ ‐free solution potently and effectively lowered this stimulated output, it was hypothesized that the Glu output is mediated by Ca2+ influx in nerve terminals. When the slices were incubated for 30 minutes under ischemic state, daurisoline caused only small alterations in the postischemic accumulation of Glu. However, Glu accumulation was markedly attenuated by H‐7, but not by calmidazolium, facilitated by PDB whereas 8‐bromo‐cAMP was without effect. It appears therefore that during a 30‐minute ischemic insult, protein kinase C (PKC) was involved in the Glu accumulation of supernatant. A direct demonstration of this concept was obtained by showing significant increases in PKC activation in presynaptic nerve terminals (from 1.34 ± 0.1 to 9.34 ± 0.89 U) following 30 minutes of ischemia. DNQX, a non‐NMDA receptor antagonist, potently reduced PKC activities and decreased extra Glu accumulation. Also observed was the inhibition of 1‐[3H]‐Glu uptake into synaptosomes by PDB. These results provide direct evidence that Ca2+ influx enhances Glu release, which in turn leads to inhibition of its reuptake, and is coupled with PKC activities in presynaptic nerve terminals.
Perineuronal satellitosis in the human hippocampal formation
Authors: Vijayan Vijaya K. , Zhou Shan‐Shan , Russell Michael J. , Geddes Jim , Ellis William , Cotman Carl W.
Published: May 2005

A previously unreported example of perineuronal satellitosis in the medial CA1 and adjacent subiculum in the human hippocampal formation is described. This phenomenon is characterized by a clustering of glial cells in relation to the perikarya of a subpopulation of neurons in the deep pyramidal layer and around most neurons scattered in the stratum oriens and subcortical white matter. Most of the perineuronal satellite glia were identified as oligodendrocytes based on their nuclear chromatin patterns and antigenic properties. Satellite oligodendrocytes were mostly of the medium dense variety. A type of satellite glia with nuclear features of the dark oligodendrocyte could not be identified unequivocally using the antigenic criteria employed in this study.
Hippocampal function in the rat: Cognitive mapping or vicarious trial and error?
Authors: Amsel Abram
Published: May 2005

The most prominent hypothesis of hippocampal function likens the hippocampus to a “cognitive map,” a term used by a famous learning theorist, E. C. Tolman, to explain maze learning. The usual application of this concept of cognitive map, as it applies to the hippocampus, is to what is called spatial learning, mainly in the radial‐arm maze of Olton and the Morris water maze. In a recent Hippocampus Forum, evidence for the cognitive map hypothesis was reviewed in a lead article by Nadel, followed by a series of commentaries by leading investigators of hippocampal function. This speculative commentary offers an alternative not represented in the forum—that the function of the hippocampus in spatial learning is not as a cognitive map, but that it subserves another function proposed by Tolman in his work on simple discrimination learning, vicarious trial and error, based on incipient, conflicting dispositions to approach and avoid.
Autoradiographic comparison of cholinergic and other transmitter receptors in the normal human hippocampus
Authors: Perry Elaine K. , Court Jennifer A. , Johnson Mary , Smith Carthage J. , James Victoria , Cheng Anthony V. , Kerwin Janet M. , Morris Christopher M. , Piggott Margaret A. , Edwardson James A. , Birdsall Nigel J. M. , Turner Jonathon T. , Perry Robert H.
Published: May 2005

The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is partcularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high‐affinity nicotine binding) nor muscarinic (“M1” or “M2”) cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5‐HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2–4 compared with CA1. By contrast, muscarinic M1 and M2, 5‐HT1A, benzodiazepine (including zolpidem‐insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5‐HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5‐HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum‐moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding. These observations, while reflecting the anatomical complexity of chemical signaling in the hippocampal region, indicate a unique distribution for the nicotinic receptor and suggest that the cholinergic input may specifically interact with 5‐HT and excitatory amino acid systems via 5‐HT2 and kainate receptor subtypes in governing signaling to the dentate and CA3 regions.
Induction of glial fibrillary acidic protein immunoreactivity in the rat dentate gyrus after adrenalectomy: Comparison with neurodegenerative changes using silver impregnation
Authors: Krugers Harm J. , Medema Rikje M. , Postema Folkert , Korf Jakob
Published: May 2005

In the present study we performed a light microscopic anatomical comparison of adrenalectomy (ADX)‐induced neurodegeneration using silver impregnation and reaction of astroglial cells using GFAP immunocytochemistry in the hippocampus of the rat. Three survival times following ADX were studied: 24 hours, 3 days, and 3 weeks. Twenty‐four hours following ADX we found no degenerative changes or altered GFAP immunostaining. Three days after adrenalectomy, argyrophilic somata appeared in the granular cell layer of the dentate gyrus. Argyrophilic dendrites were seen in the molecular layer of the dentate gyrus and neuritic argyrophilia were seen in the mossy fiber layer. Induction of GFAP immunoreactivity occurred simultaneously with degeneration. Increased GFAP immunoreactivity could be observed 3 days after adrenalectomy in the molecular layer of the dentate gyrus, granular cell layer, sub and supragranular cell layer, and mossy fiber layer. Size and shape of astroglial cells were changed, and their processes in the molecular layer changed from unidirectional to randomly organized. Degeneration and astroglial reaction were more pronounced 3 weeks after adrenalectomy and both were prevented by adding corticosterone to the drinking solution. Animals that did not show degenerative changes showed no increased GFAP immunoreactivity, while both effects were confined to the dentate gyrus and mossy fiber zone. These results show that there is a close relationship between the induction of GFAP immunoreactivity in the hippocampus of the rat and neuronal degeneration in the dentate gyrus following ADX, both in time and space. © 1994 Wiley‐Liss, Inc.
Potassium‐induced long‐term potentiation in area CA1 of the hippocampus involves phospholipase activation
Authors: Bernard Julie , Lahsaini Ahmed , Massicotte Guy
Published: May 2005

Previous studies have shown that potassium‐induced long‐term potentiation (LTP) of the Schaffer collateral/commissural synapses in area CA1 of the hippocampus shares common properties with tetanus‐induced LTP. In the present investigation, we performed electrophysiological and binding experiments on CA1 hippocampal slices to evaluate the location and nature of the changes underlying potassium‐induced LTP. Paired‐pulse facilitation, which represents an index of transmitter release, was markedly reduced by potassium‐induced LTP. In addition, KC1‐induced LTP was associated with an increase in 3H‐AMPA ([3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate) binding to CA1 synaptic membranes when measured 40 min after high‐potassium exposure; however, no changes were detected in binding of an antagonist ([3H]‐6‐cyano‐7‐nitroquinoxaline‐2,3‐dione; 3H‐CNQX) to AMPA receptors in slices expressing KC1‐induced LTP. Administration of the phospholipase A2 (PLA2) inhibitor bromophenacyl bromide (BPB) prior to potassium application prevented LTP formation as well as the changes in paired‐pulse facilitation and 3H‐AMPA binding that characterized this type of potentiation. Taken together, these data indicate that potassium‐in‐duced LTP may be related to modifications in both pre‐and postsynaptic properties and confirm the hypothesis that PLA2 activation is an important mechanism in long‐term changes of synaptic operation. © 1994 Wiley‐Liss, Inc.
Genetic and activity‐dependent regulation of Zif268 expression: Association with spatial learning
Authors: Fordyce Diana E. , Bhat Ratan V. , Baraban Jay M. , Wehner Jeanne M.
Published: May 2005

We have reported that C57BL/6 and DBA/2 mice differ in spatial learning performance and associated hippocampal protein kinase C (PKC) activity (Upchurch and Wehner, 1989, Behav Neurosci 103:1251–1258; Wehner et al., 1990, Brain Res 523:181–187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) (Fordyee and Wehner, 1993b, Brain Res 619:111–119). To assess whether physical activity induces alterations in gene expression that may underlie these changes in PKC and learning performance, we examined the effect of physical activity on expression of zif268, a transcription regulatory factor linked to stimulus‐induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chronic (8 weeks) physical activity. The mice were then tested on the Morris water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocampal‐specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523:181–187; Fordyce and Wehner, 1993b, Brain Res 619:111–119; Paylor et al., 1993, Psychobiology 27:11–26), displayed lower basal levels of zif268 mRNA (P <.05). As observed previously, chronic physical activity produced an enhancement in spatial learning performance accompanied by alterations in hippocampal PKC activity in both strains of mice (P <.05). In addition, the present investigation demonstrated that acute physical increased mRNA levels of zif268 in hippocampal regions CA1, CA3 and overlying cortex (P <.005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity‐dependent regulation of zif268 may influence learning performance. © 1994 Wiley‐Liss, Inc.
Development of inhibitory and excitatory synaptic transmission in the rat dentate gyrus
Authors: DiScenna Pascal G. , Teyler Timothy J.
Published: May 2005

We studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired‐pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired‐pulse responses across a wide range of interpulse intervals (IPI). Paired‐pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN > 60.

The synaptic paired‐pulse profile (10–5,000 ms IPI) matured by PN7/8. The triphasic pattern of short‐latency depression, a relative facilitation at intermediate intervals, and long‐latency depression was present at all ages tested. Paired‐pulse effects on granule cell discharge indicated the presence of weak short‐latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short‐latency inhibition was statistically equivalent to the mature dentate gyrus. Long‐latency (500–2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40–120 ms) where spike facilitation was significantly depressed in the developmental groups.

The studies indicate that short‐term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early age. © 1994 Wiley‐Liss, Inc.
Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: II. Alterations in somatic synapses
Authors: Bundman Marsha C. , Gall Christine M.
Published: May 2005

Hilus lesion‐induced recurrent limbic seizures cause a dramatic increase in the numbers of somatic spines on dentate gyrus granule cells in the adult rat. Somatic spines are maximally increased 3 h after the initiation of seizures at which time many of these spines form synapses. The present quantitative electron microscopic study assessed the numbers and types of synapses present on the granule cell perikarya and somatic spines of control and experimental seizure rats with the goal of determining if newly elaborated somatic spines arise at the site of pre‐existing synapses or are associated with new innervation. Experimental rats were sacrificed 5 h after hilar lesion placement (or 3 h after seizure onset). In both control and hilus‐lesioned (HL) rats, 15–20% of the somatic spines could be seen to form synaptic contacts within a single plane of section; these synapses were almost exclusively of the asymmetric type. With the increased incidence of spines in experimental‐seizure rats, there was a 6.25‐fold greater number of spine synapses in HL versus control rats. There was, in addition, a 60% decrease in the number of asymmetric synapses occurring directly on the granule cell perikarya but no change in the total (spine plus somatic) number of asymmeteric synapses. Although few asymmetric synapses were associated with spines in control tissue, 60–70% of asymmetric synapses were associated with spines in experimental‐seizure tissue. In addition, in hilus lesion rats symmetric somatic synapses were increased by 20% on cells in deep stratum granulosum resulting in a dissolution of the superficial‐to‐deep innervation gradient present in the untreated rat. These findiings support the conclusion that spines induced by seizure activity form at the site of pre‐existing asymmetric synapses on the granule cells and demonstrate that brief seizure episodes can rapidly induce marked changes in innervation patterns in the adult brain. © 1994 Wiley‐Liss, Inc.