bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of idebenone and α‐tocopherol on β‐amyloid‐(1–42)‐induced learning and memory deficits in rats: implication of oxidative stress in β‐amyloid‐induced neurotoxicity in vivo
Authors: Yamada Kiyofumi , Tanaka Tomoko , Han Daiken , Senzaki Kouji , Kameyama Tsutomu , Nabeshima Toshitaka 
Published: March 2003

AbstractAmyloid β‐peptide (Aβ), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of Aβ‐induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of Aβ‐(1–42). In the Aβ‐(1–42)‐infused rats, spontaneous alternation behaviour in a Y‐maze and spatial memory in a water maze task were significantly impaired, as compared with Aβ‐(40–1)‐infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with Aβ‐(1–42). Potent antioxidants idebenone and α‐tocopherol prevented the behavioural deficits in Y‐maze and water maze, but not passive avoidance, tasks in Aβ‐(1–42)‐infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of Aβ infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of Aβ‐(1–42)‐infused rats did not differ from those in control animals, and neither idebenone nor α‐tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and α‐tocopherol prevents learning and memory deficits caused by Aβ.
Poly(ADP ribose) polymerase cleavage precedes neuronal death in the hippocampus and cerebellum following injury to the developing rat forebrain
Authors: Joashi U. C. , Greenwood K. , Taylor D. L. , Kozma M. , Mazarakis N. D. , Edwards A. D. , Mehmet H. 
Published: March 2003

AbstractTransient unilateral forebrain hypoxia–ischaemia (HI) in 14‐day‐old rats produces infarction and delayed neuronal death in the frontal cortex. Cell death can also be observed in regions distant from the primary injury, a phenomenon known as diaschisis. While apoptosis is involved in selective neuronal death, its role in infarction and diaschisis remains poorly understood. Here, we have investigated the proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and the occurrence of apoptosis in the hippocampus and the cerebellum following either HI or traumatic brain injury. We demonstrate that: (i) in vitro, PARP is cleaved during apoptosis but not necrosis in cultured neuronal (N1E) cells and Swiss 3T3 fibroblasts; (ii) following HI, apoptotic cells can be detected by 4 h after injury in the hippocampus; (iii) in the ipsilateral hippocampus the appearance of cells with apoptotic morphology is preceded by a dramatic increase in PARP cleavage in the same region, starting immediately following HI and persisting for 24 h; (iv) HI also induces apoptosis in the cerebellum and, as in the hippocampus, the appearance of cells with apoptotic morphology is preceded by PARP cleavage that is greater on the side Ipsilateral to forebrain injury; and (v) similarly, traumatic brain injury to the forebrain leads to PARP cleavage and apoptosis in the cerebellum. We conclude that HI injury or traumatic injury to the developing rat forebrain leads to PARP cleavage in directly affected areas and in sites distant from the primary injury that precedes the appearance of cells with apoptotic morphology. Our results are consistent with a role for apoptotic cell death in infarction and in diaschisis resulting from forebrain injury to the developing brain.
Glutamate receptor phenotypes in the auditory brainstem and mid‐brain of the developing rat
Authors: Caicedo Alejandro , Eybalin Michel 
Published: March 2003

AbstractGlutamate receptors mediate most excitatory synaptic transmission in the adult vertebrate brain, but their activation in developing neurons also influences developmental processes. However, little is known about the developmental regulation of the subunits composing these receptors. Here we have studied age‐dependent changes in the expression of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole (AMPA) andN‐methyl‐d‐aspartate (NMDA) receptor subunits in the cochlear nucleus complex (CN), the superior olivary complex (SOC), the nuclei of the lateral lemniscus, and the inferior colliculus of the developing rat. In the lateral superior olive, the medial nucleus of the trapezoid body, and the ventral nucleus of the lateral lemniscus, the distribution of AMPA receptor subunits changed drastically with age. While GluR1 and GluR2 subunits were highly expressed in the first 2 postnatal weeks, GluR4 staining was detectable only thereafter. GluR1 and GluR2 immunoreactivities rapidly decreased during the third postnatal week, with the GluR1 subunits disappearing from most neurons. In contrast, the adult pattern of the distribution of AMPA receptor subunits emerged gradually in most of the other auditory nuclei. Thus, progressive as well as regressive events characterized AMPA receptor development in some nuclei, while a monotonically maturation was seen in other regions. In contrast, the staining patterns of NMDA receptor subunits remained stable or only decreased during the same period. Although our data are not consistent with a generalized pattern of AMPA receptor development, the abundance of GluR1 subunits is a distinctive feature of early AMPA receptors. As similar AMPA receptors are present during plasticity periods throughout the brain, neurons undergoing synaptic and structural remodelling might have a particular need for these receptors.
The medullary dorsal reticular nucleus facilitates pain behaviour induced by formalin in the rat
Authors: Almeida A. , Størkson R. , Lima D. , Hole K. , Tjølsen A. 
Published: March 2003

AbstractThe influence of the dorsal reticular nucleus (DRt) on pain behaviour during the formalin test was studied in the rat by lesioning the nucleus through local application of electrical current or quinolinic acid. Animals in which the DRt was lesioned ipsilaterally to the paw injected with formalin spent less time in focused (licking, biting or scratching the injected paw) and total (focused pain behaviour plus protection of the injected paw during movements) pain behaviour, and showed paw‐jerks less frequently than non‐lesioned animals in both phases 1 and 2 of the test. Animals in which the DRt was lesioned contralaterally to the injected paw presented a decrease in total pain behaviour and number of paw‐jerks only during phase 2. The number of superficial (laminae I–II) and deep (laminae III–VI) spinal dorsal horn cells expressing the c‐fos proto‐oncogene 2 h after subcutaneous injection of formalin was reduced by 34% and 50%, respectively, in animals with an ipsilateral DRt lesion as compared to non‐lesioned rats. No differences in c‐fos expression were observed after lesioning the DRt contralateral to the formalin injection. The results indicate that the DRt is involved in the facilitation of nociception during the formalin test by enhancing the response capacity of dorsal horn neurons to noxious stimulation. It is suggested that the pronociceptive action of the DRt is mediated by the reciprocal connections it establishes with the spinal dorsal horn [Almeida et al. (1993) Neuroscience, 55, 1093].
Protein kinase C modulates field‐evoked transmitter release from cultured rat cerebellar granule cells via a dendrotoxin‐sensitive K+ channel
Authors: Cousin Michael A. , McLaughlin Mark , Nicholls David G. 
Published: March 2003

AbstractThe role of protein kinase C (PKC) in the control of neurotransmitter release from cultured rat cerebellar granule cells was investigated. Release of preloaded [3H]‐d‐aspartate which is incorporated into synaptic vesicles in this preparation was evoked by electrical field stimulation or elevated KCl. PKC activation by phorbol esters resulted in a large facilitation of field‐evoked Ca2+‐dependent [3H]‐d‐aspartate release and a lesser enhancement of KCl‐stimulated release. Inhibition of PKC by Ro 31‐8220 or staurosporine virtually abolished field‐evoked release but had no effect on KCl‐evoked release. Field‐evoked, but not KCl‐evoked, synaptic vesicle exocytosis monitored by the fluorescent vesicle probe FM2‐10 was inhibited by staurosporine. PKC was not directly modulating neurite Ca2+ channels coupled to release, as Ro 31‐8220 did not inhibit these channels. Activation or inhibition of PKC modulated field‐evoked plasma membrane depolarization, but had no effect on KCl‐evoked depolarization, consistent with a regulation of Na+ or K+ channels activated by field stimulation. No modulation of field‐evoked neurite Na+ influx was seen using phorbol esters. Phorbol ester‐induced facilitation of field‐evoked [3H]‐d‐aspartate release and neurite Ca2+ entry was non‐additive with that produced by the specific K+ channel antagonist dendrotoxin‐1, suggesting that PKC modulates transmitter release from field‐stimulated cerebellar granule cells by inhibiting a dendrotoxin‐1‐sensitive K+ channel.
CaMKII‐dependent phosphorylation of NR2A and NR2B is decreased in animals characterized by hippocampal damage and impaired LTP
Authors: Caputi A. , Gardoni F. , Cimino M. , Pastorino L. , Cattabeni F. , Di Luca M. 
Published: March 2003

AbstractThe calcium‐calmodulin‐dependent protein kinase II (CaMKII) subserves activity‐dependent plasticity in central neurons. To examine in vivo the implication of CaMKII activity in synaptic plasticity, we used an animal model characterized by developmentally induced targeted neuronal ablation within the cortex and the hippocampus, and showing, at presynaptic level, molecular alterations leading to facilitation of glutamate release in hippocampal synapses (methylazoxymethanol‐treated rats, MAM‐rats). We report here that at the postsynaptic side, the activity of CaMKII is markedly decreased in MAM‐rats when compared to controls, although the concentration of the enzyme in Post Synaptic Density (PSD) is not altered. This effect is confined to PSD‐associated CaMKII, as enzyme activity tested in the soluble fraction is unchanged in MAM‐rats. In addition, the decreased activity is not due to inhibition by autophosphorylation in specific sites within the calmodulin‐binding domain, as preincubation with purified phosphatases 1 and 2A failed to restore CaMKII activity in PSD of MAM‐rats. The CaMKII‐dependent phosphorylation of NR2A/B subunits of NMDA receptor is lower in MAM‐rats when compared to controls (51.77 ± 7.39% of controls level), as revealed in back‐phosphorylation experiments. In addition, a treatment able to restore long‐term potentiation (LTP) in hippocampal slices from MAM‐rats, e.g. exposure to d‐serine, is able to restore CaMKII activity to the control value.
Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin
Authors: Okada Motohiro , Kawata Yuko , Murakami Takuya , Wada Kazumaru , Mizuno Kazuhisa , Kondo Tuyoshi , Kaneko Sunao 
Published: March 2003

AbstractTo clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5‐HT) release and 5‐HT reuptake activity, hippocampal extracellular 5‐HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5‐HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5‐HT levels. Adenosine and A1 receptor agonist, 2‐chloro‐N6‐cyclopentyl‐adenosine (CCPA), decreased extracellular 5‐HT levels, whereas non‐selective antagonist, caffeine, and A1 antagonist, 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT) increased them. When 5‐HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5‐HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7‐dimethyl‐1‐propargylxanthine (DMPX), and A3 receptor agonist, N6–2‐(4‐aminophenyl)ethyladenosine (APNEA) did not affect 5‐HT levels; however, when A1 receptor was blocked by CPT, 5‐HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5‐HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5‐HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5‐HT reuptake activity might be modulated by hippocampal A3 receptor.
TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation
Authors: Pizzorusso Tommaso , Berardi Nicoletta , Rossi Francesco M. , Viegi Alessandro , Venstrom Kristine , Reichardt Louis F. , Maffei Lamberto 
Published: March 2003

AbstractIt has been recently shown that intraventricular injections of nerve growth factor (NGF) prevent the effects of monocular deprivation in the rat. We have tested the localization and the molecular nature of the NGF receptor(s) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA, the bivalent antirat trkA IgG (RTA‐IgG). TrkA protein was detected by immunoblot in the rat visual cortex during the critical period. Rats were monocularly deprived for 1 week (P21–28) and RTA‐IgG or control rabbit IgG were delivered by osmotic minipumps. The effects of monocular deprivation on the ocular dominance of visual cortical neurons were assessed by extracellular single cell recordings. We found that the shift towards the ipsilateral, non‐deprived eye was largely prevented by RTA‐IgG. Infusion of RTA‐IgG combined with antibody that blocks p75NTR (REX), slightly reduced RTA‐IgG effectiveness in preventing monocular deprivation effects. These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75NTR exerting a facilitatory role.
Chloride‐dependent transport of NH4+ into bee retinal glial cells
Authors: Marcaggi Païkan , Thwaites David T. , Deitmer Joachim W. , Coles Jonathan A. 
Published: March 2003

AbstractMammalian astrocytes convert glutamate to glutamine and bee retinal glial cells convert pyruvate to alanine. To maintain such amination reactions these glial cells may take up NH4+/NH3. We have studied the entry of NH4+/NH3 into bundles of glial cells isolated from bee retina by using the fluorescent dye BCECF to measure pH. Ammonium caused intracellular pH to decrease by a saturable process: the rate of change of pH was maximal for an ammonium concentration of about 5 mm. This acidifying response to ammonium was abolished by the loop diuretic bumetanide (100 μm) and by removal of extracellular Cl–. These results strongly suggest that ammonium enters the cell by cotransport of NH4+ with Cl–. Removal of extracellular Na+ did not abolish the NH4+‐induced acidification. The NH4+‐induced pH change was unaffected when nearly all K+ conductance was blocked with 5 mm Ba2+ showing that NH4+ did not enter through Ba2+‐sensitive ion channels. Application of 2 mm NH4+ led to a large increase in total intracellular proton concentration estimated to exceed 13.5 mEq/L. As the cell membrane appeared to be permeable to NH3, we suggest that when NH4+ entered the cells, NH3 left, so that protons were shuttled into the cell. This shuttle, which was strongly dependent on internal and external pH, was quantitatively modelled. In retinal slices, 2 mm NH4+ alkalinized the extracellular space: this alkalinization was reduced in the absence of bath Cl–. We conclude that NH4+ enters the glial cells in bee retina on a cotransporter with functional similarities to the NH4+(K+)‐Cl– cotransporter described in kidney cells.
Pontine and medullary control of the respiratory activity in the trigeminal and facial nerves of the newborn mouse: an in vitro study
Authors: Jacquin Thierry Didier , Sadoc Gérard , Borday Véronique , Champagnat Jean 
Published: March 2003

AbstractIn vitro, the respiratory activity in rodents is characterized by: (i) the rapidly peaking, slowly decrementing pattern of spontaneous and rhythmic active phases recorded from the motor rootlets, and (ii) the specific location of their rhythmic generator in the ventrolateral medulla. The aim of the present study was to assess whether the trigeminal and facial motor rootlets still exhibit respiratory activity in the absence of peripheral and higher cerebral structures, and to compare the onset of their active phases with that of other respiratory rootlets, using the in vitro isolated brainstem–spinal cord preparation of the newborn mouse and rat. Spontaneous rhythmic activity was recorded from the trigeminal and facial rootlets. It was regular and synchronized bilaterally and ipsilaterally with the hypoglossal or cervical C1–C6 rootlets. Brainstem transection experiments demonstrated that for both the trigeminal and facial rootlets, the spontaneous rhythmic activity originates from the medulla, in a region consistent with the pre‐Bötzinger complex and the rostral ventrolateral medulla. The pattern of the respiratory motor activity recorded from the trigeminal and facial rootlets was identical to the pattern recorded from the hypoglossal and cervical C1–C6 rootlets with rapidly peaking, slowly decrementing characteristics. The duration of the ascending part and the total duration of their active phases were similar. The onset of the active phases of the phrenic rootlets was delayed compared with that of the trigeminal, facial and hypoglossal rootlets. However, no difference in the onsets of the active phases of the cranial rootlets could be observed. Removal of the rostral pons suppressed the delay in onset of the active phases of the phrenic rootlets. Our findings show that: (i) rhythmic activities of the trigeminal and facial rootlets are preserved in absence of control by peripheral or high cerebral structures; (ii) the pattern and the location of the rhythmic generator for these activities are of the respiratory type; and (iii) the rostral pons is responsible for a delay in the onset of the active phases of the phrenic rootlets compared with that of the trigeminal, facial and hypoglossal rootlets.
Cerebellar granule‐cell‐specific GABAA receptors attenuate benzodiazepine‐induced ataxia: evidence from α6‐subunit‐deficient mice
Authors: Korpi Esa R. , Koikkalainen Paula , Vekovischeva Olga Y. , Mäkelä Riikka , Kleinz Raymonde , Uusi‐Oukari Mikko , Wisden William 
Published: March 2003

AbstractBenzodiazepine‐ and alcohol‐induced ataxias in rodents have been proposed to be affected by the γ‐aminobutyric acid type A (GABAA) receptor α6 subunit, which contributes to receptors specifically expressed in cerebellar granule cells. We have studied an α6 –/– mouse line for motor performance and drug sensitivity. These mice, as a result of a specific genetic lesion, carry a precise impairment at their Golgi‐granule cell synapses. On motor performance tests (rotarod, horizontal wire, pole descending, staircase and swimming tests) there were no robust baseline differences in motor function or motor learning between α6 –/– and α6 +/+ mice. On the rotarod test, however, the mutant mice were significantly more impaired by diazepam (5–20 mg/kg, i.p.), when compared with α6 +/+ control and background C57BL/6J and 129/SvJ mouse lines. Ethanol (2.0–2.5 g/kg, i.p.) produced similar impairment in the α6 –/– and α6 +/+ mice. Diazepam‐induced ataxia in α6 –/– mice could be reversed by the benzodiazepine site antagonist flumazenil, indicating the involvement of the remaining α1β2/3γ2 GABAA receptors of the granule cells. The level of activity in this synapse is crucial in regulating the execution of motor tasks. We conclude that GABAA receptor α6 subunit‐dependent actions in the cerebellar cortex can be compensated by other receptor subtypes; but if not for the α6 subunit, patients on benzodiazepine medication would suffer considerably from ataxic side‐effects.
Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat
Authors: Linke Rüdiger 
Published: March 2003

AbstractThe thalamic nuclei at the medial border of the medial geniculate body (i.e. the suprageniculate nucleus, the medial division of the medial geniculate nucleus, the posterior intralaminar nucleus and the peripeduncular nucleus) which relay sensory information to the amygdala are thought to receive convergent input from multiple sites. In order to delineate the organization of these multimodal thalamic nuclei, the locations of superior and inferior collicular neurons projecting to these nuclei were studied by means of retrograde transport methods. Small injections of the tracer Miniruby were made into single paralaminar thalamic nuclei. Injections of Miniruby into the suprageniculate nucleus labelled predominantly neurons in the stratum opticum of the superior colliculus, whereas injections into the medial division of the medial geniculate body, the posterior intralaminar nucleus and the peripeduncular nucleus labelled predominantly neurons in the deep layers of the superior colliculus. These injections also labelled neurons in the inferior colliculus. The majority of retrogradely labelled neurons were found in the external nucleus of the inferior colliculus and here predominantly in layer 2. Injections focused onto the medial division of the medial geniculate body additionally labelled magnocellular neurons in layer 3 of the external nucleus and a few neurons in the central nucleus. More ventrally located injections, focused onto the posterior intralaminar and peripeduncular nucleus, almost exclusively labelled neurons in layer 1 of the external nucleus and the dorsal part of the dorsal nucleus. After injections into the suprageniculate nucleus, only neurons in layer 2 were found. Neurons in the central nucleus of the inferior colliculus were only found after injections that involved the medial division of the medial geniculate body. The present results suggest that, despite a considerable degree of convergence in this thalamic region, each of these thalamic nuclei receives a unique pattern of projections from the superior and inferior colliculi. It appears that the thalamic nuclei may be concerned mainly, but not exclusively, with a single sensory modality, and give rise to parallel multimodal and unimodal pathways to the amygdala.