bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of soil physical and chemical properties on the sorption‐desorption hysteresis of the diketonitrile metabolite of isoxaflutole
Authors: MITRA SOWMYA , BHOWMIK PRASANTA C. , XING BAOSHAN
Published: May 2003

Isoxaflutole, [4‐(2‐methanesulfonyl‐4‐trifluoromethylbenzoyl)‐5‐cyclopropyl isoxazole] is a relatively new pre‐emergence herbicide which undergoes rapid conversion to a diketonitrile metabolite in soil. The half‐life of isoxaflutole is very short but the half‐life of diketonitrile is much longer and hence, diketonitrile remains for a extended period of time in soil. Sorption‐desorption studies were conducted with five soils varying in physical and chemical properties. The batch equilibration technique was used for the sorption experiments, while completely mixed batch reactor systems with the decant and refill method was used for the desorption experiments. Four subsequent desorptions were examined after the sorption process in each soil with an equilibration period of seven days. An apparent sorption‐desorption hysteresis was observed in all five soils. Organic matter content and the clay content of the soils were the two determining factors for hysteresis. In soils with high organic matter content, the sorption‐desorption hysteresis was mainly governed by organic matter content, but in soils with low organic matter clay content played an important role. With the exception of the Chelsea soil, which had a very high organic matter content (57.4%), all other soils exhibited a high correlation between the clay content and hysteresis index (HI) values calculated at 0.75 (r2 = 0.960), 25 (r2 = 0.934) and 150 mg L−1 (r2 = 0.928). In conclusion, the potential for leaching through soil and crop injury due to isoxaflutole and its metabolite would decrease as soil organic matter and clay content increases.
Alfalfa, rice by‐products and their incorporation for weed control in rice
Authors: XUAN TRAN DANG , TSUZUKI EIJI , TERAO HIROYUKI , MATSUO MITSUHIRO , KHANH TRAN DANG , MURAYAMA SEIICHI , HONG NGUYEN HUU
Published: May 2003

Two alfalfa varieties, namely Rasen and Yuba, and rice by‐products of Koshihikari (Oryza sativa L. cv. Japonica), including hull and bran were used for weed control in rice. Rasen and Yuba were sequentially evaluated to have the strongest allelopathic potential among eight common alfalfa varieties in Japan. Rasen, Yuba and rice by‐products in a laboratory experiment exhibited suppression of emergence of lettuce (Lactuca sativa L.), barnyardgrass (Echinochloa oryzicola Vasing.), and monochoria (Monochoria vaginalis Presl var. plantaginea Solms‐Laub.). In a paddy field experiment, at 15 days after application, a dose of 1 ton ha−1 of alfalfa, rice by‐products and the incorporated alfalfa‐rice by‐products significantly inhibited weed growth and reduced weed species, except for rice bran. However, at 40 days after application, the greatest weed control was sequentially recorded with Yuba (95.2%), Rasen (90.5%) and the incorporated Rasen‐hull (88.3%). Rice hull exhibited stronger (51.7%) weed control than the negligible weed control of rice bran (25.1%). Inhibition of both Rasen and Yuba on weed emergence after application became more vigorous, whereas those of rice by‐products were gradually devitalized. Rasen had a maximum increase of rice yield (80.6%) compared to the control and it was slightly higher (9.6%) than the herbicide treatment. Findings showed that Rasen was the most promising material for weed control among those studied. Results denoted that weed control capability of allelopathic materials had an impetuous effect on rice growth and yield.
Associative mossy fibre LTP induced by pairing presynaptic stimulation with postsynaptic hyperpolarization of CA3 neurons in rat hippocampal slice
Authors: Sokolov Maxim V. , Rossokhin Alexej V. , M. Kasyanov Alexander , Gasparini Sonia , Berretta Nicola , Cherubini Enrico , Voronin Leon L.
Published: May 2003

Whole cell recordings of excitatory postsynaptic potentials/currents (EPSPs/EPSCs) evoked by minimal stimulation of commissural–associative (CF) and mossy fibre (MF) inputs were performed in CA3 pyramidal neurons. Paired responses (at 50 ms intervals) were recorded before, during and after hyperpolarization of the postsynaptic membrane (20–30 mV for 15–35 min). Membrane hyperpolarization produced a supralinear increase of EPSPs/EPSCs amplitude in MF‐inputs. Synaptic responses remained potentiated for the rest of the recording period (up to 40 min) after resetting the membrane potential to control level (221 ± 60%, n = 15 and 219 ± 61%, n = 11 for MF‐EPSP and MF‐EPSC, respectively). We shall refer to this effect as hyperpolarization‐induced LTP (HI‐LTP). In the absence of afferent stimulation, membrane hyperpolarization was unable to produce HI‐LTP. In contrast to MF‐EPSPs, the mean amplitude of CF‐EPSPs did not increase significantly after hyperpolarization relative to controls (138 ± 29%, n = 22). HI‐LTP was associated with modifications of classical indices of presynaptic release: paired‐pulse facilitation, failures rate, coefficient of variation of EPSP amplitudes and quantal content. The induction of HI‐LTP was NMDA independent but was dependent on metabotropic glutamate receptors (mGluRs) activation and calcium release from inositol 1,4,5‐triphosphate (IP3)‐sensitive intracellular stores: it was prevented by mGluR antagonist, intracellular heparin and BAPTA. We conclude that while the induction of HI‐LTP was postsynaptic, its expression was presynaptic.
Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin‐1β
Authors: Crane J. W. , Ebner K. , Day T. A.
Published: May 2003

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic–pituitary–adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin‐releasing factor cells at the apex of the hypothalamic–pituitary–adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin‐1β. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic–pituitary–adrenal axis responses to systemic interleukin‐1β, we next mapped the effects of similar lesions on interleukin‐1β‐induced Fos expression in regions previously shown to regulate the hypothalamic–pituitary–adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos‐positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis‐projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin‐1β, an outcome that is difficult to reconcile with a simple medial prefrontal cortex–bed nucleus of the stria terminalis–corticotropin‐releasing factor cell control circuit.
Agonistic encounters in aged male mouse potentiate the expression of endogenous brain NGF and BDNF: possible implication for brain progenitor cells' activation
Authors: Fiore Marco , Amendola Tiziana , Triaca Viviana , Tirassa Paola , Alleva Enrico , Aloe Luigi
Published: May 2003

The condition of dominance or submission following agonistic encounters in the adult male mouse is known to differentially affect brain nerve growth factor, a neurotrophin playing a role in brain remodeling, in the fine tuning of behaviour and in the regulation of the basal forebrain cholinergic neurons. During development and adult life nerve growth factor regulates brain expression of neurotransmitters and the stimulation of progenitor cells (stem cells) which, under different external stimuli, may differentiate into neuronal and/or glial cells promoting the recovery of the injured brain. However, little information is available for the aged brain. Thus in the present study we investigated the effect of the social status (‘dominance’ vs. ‘submission’) in the aged mouse on the presence of nerve growth factor, brain‐derived neurotrophic factor, choline acetyltransferase, neuropeptide Y and progenitor cells of selected brain regions. We found that aged dominant mice showed increased brain‐derived neurotrophic factor in the subventricular zone and hippocampus and increased choline acetyltransferase in the septum and basal nuclei, which were associated with increased presence of progenitor cells in the subventricular zone. Conversely, in aged subordinate mice the data showed a marked brain increase in nerve growth factor in the subventricular zone and hippocampus, choline acetyltransferase in the septum and basal nuclei and neuropeptide Y in the hippocampus and parietal cortex. The possible functional implications of these findings are discussed.
Attenuation of neuropathic pain by the nociceptin/orphanin FQ antagonist JTC‐801 is mediated by inhibition of nitric oxide production
Authors: Mabuchi Tamaki , Matsumura Shinji , Okuda‐Ashitaka Emiko , Kitano Takahiro , Kojima Hirotatsu , Nagano Tetsuo , Minami Toshiaki , Ito Seiji
Published: May 2003

At the spinal level, the involvement of nociceptin/orphanin FQ (N/OFQ) in pain transmission is controversial. JTC‐801, a selective nonpeptidergic N/OFQ antagonist, is a good tool to examine the involvement of endogenous N/OFQ in pathophysiological conditions. In the present study, we studied the effect of JTC‐801 on neuropathic pain induced by L5 spinal nerve transection in mice. Thermal hyperalgesia was evident on day 3 postsurgery and maintained during the 10‐day experimental period. Oral administration of JTC‐801 relieved the thermal hyperalgesia in neuropathic mice in a dose‐dependent manner. Following L5 nerve transection, the increase in nitric oxide synthase (NOS) activity was observed in the superficial layer of dorsal horn and around the central canal in the spinal cord by NADPH diaphorase histochemistry. Using the novel fluorescent nitric oxide (NO) detection dye diaminofluorescein‐FM, we confirmed that NO production increased in the spinal slice prepared from neuropathic mice and that the increase was more prominent in the ipsilateral side to the nerve transection than in the contralateral side. These increases in NOS activity and NO production in neuropathic mice were blocked by pretreatment of oral JTC‐801. Although intraperitoneal injection of the nonselective NOS inhibitor NG.‐nitro‐L‐arginine methyl ester transiently, but significantly, attenuated neuropathic hyperalgesia, inducible NOS‐deficient mice showed neuropathic pain after L5 spinal nerve transection. These results suggest that N/OFQ is involved in the maintenance of neuropathic pain and that the analgesic effect of JTC‐801 on neuropathic pain is mediated by inhibition of NO production by neuronal NOS.
Systemic or intra‐amygdala injections of glucose facilitate memory consolidation for extinction of drug‐induced conditioned reward
Authors: Schroeder Jason P. , Packard Mark G.
Published: May 2003

The conditioned place preference (CPP) task has been used extensively to investigate the neurobiological bases of drug‐induced reward. The initial expression of a CPP involves memory for an association between environmental stimuli and the affective state produced by a rewarding treatment. The present experiments examined the hypothesis that post‐trial administration of glucose can facilitate memory consolidation processes underlying the extinction of drug‐induced CPP behaviour. Adult male Long‐Evans rats acquired an amphetamine CPP, and subsequently received extinction training. Immediately following extinction training, separate groups of rats received peripheral (100 mg/kg, 500 mg/kg, or 2 g/kg) or intra‐amygdala (basolateral nucleus; 1.5 µg/0.5 µL or 10 µg/0.5 µL) injections of glucose or vehicle. Peripheral (100 mg/kg and 2 g/kg) and intra‐amygdala (1.5 and 10 µg) glucose injections facilitated the extinction of amphetamine CPP behaviour relative to vehicle‐injected controls. Postextinction trial peripheral or intra amygdala glucose injections that were delayed 2 h had no effect. The findings indicate that: (i) extinction of approach behaviour to drug‐associated cues involves the formation of new memories that undergo a time‐dependent consolidation process; and (ii), systemic or intra‐amygdala administration of a known memory‐enhancing agent facilitates extinction of drug‐induced CPP behaviour.
p53 Inactivation leads to impaired motor synchronization in mice
Authors: Campana Aline L. M. , Rondi‐Reig Laure , Tobin Christine , Lohof Ann M. , Picquet Florence , Falempin Maurice , Weitzman Jonathan B. , Mariani Jean
Published: May 2003

We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53‐null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo‐cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin‐α, into the cerebellum of wild‐type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.
Individual differences in prefrontal cortical activation on the Tower of London planning task: implication for effortful processing
Authors: Cazalis F. , Valabrègue R. , Pélégrini‐Issac M. , Asloun S. , Robbins T. W. , Granon S.
Published: May 2003

Solving challenging (‘effortful’) problems is known to involve the dorsal and dorsolateral prefrontal cortex in normal volunteers, although there is considerable individual variation. In this functional magnetic resonance imaging study, we show that healthy subjects with different levels of performance in the Tower of London planning task exhibit different patterns of brain activation. All subjects exhibited significant bilateral activation in the dorsolateral prefrontal cortex, the anterior and posterior cingulate areas and the parietal cortex. However, ‘standard performers’ (performance < 70% correct) and ‘superior performers’ (performance >70% correct) differed in the patterns of activation exhibited. Superior performers showed a significantly more spatially extended activation in the left dorsolateral prefrontal cortex than did standard performers, whereas the latter group tended to show increased activation of the anterior cingulate region.
HCN channels are expressed differentially in retinal bipolar cells and concentrated at synaptic terminals
Authors: Müller Frank , Scholten Alexander , Ivanova Elena , Haverkamp Silke , Kremmer Elisabeth , Kaupp U. Benjamin
Published: May 2003

Hyperpolarization‐activated and cyclic nucleotide‐gated (HCN) channels codetermine the integrative behaviour of neurons and shape their response to synaptic stimulation. We used immunohistochemistry and patch‐clamp recording to study the composition and distribution of HCN channels in the rat retina. All four HCN channel isoforms (HCN1–4) are expressed differentially in the retina. In particular, different classes of bipolar cells have a different inventory of HCN channels. We found no evidence for the formation of heterooligomeric HCN channels. HCN channels are densely clustered at synaptic terminals of bipolar cells and photoreceptors. This suggests that HCN channels are involved in the control of transmitter release.
Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self‐administration
Authors: Fagergren P. , Smith H. R. , Daunais J. B. , Nader M. A. , Porrino L. J. , Hurd Y. L.
Published: May 2003

Several human and rat studies suggest that the striatal dynorphin system is important for neuroadaptation following cocaine exposure. In the current study, prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and chronic phases of cocaine self‐administration. Adult Rhesus monkeys were trained to self‐administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg per injection) on a fixed interval 3‐min schedule for 5 or 100 sessions. Each session ended after 30 reinforcers were delivered. The PDYN mRNA expression was analysed in the precommissural striatum using in situ hybridization histochemistry. We found a specific activation of PDYN mRNA expression in the limbic‐innervated patch/striosome compartment of the dorsal caudate and dorsal putamen during the initial (i.e. 5 day) phase of the high dose cocaine self‐administration. After 100 days of the high dose exposure, the patch/striosome compartment remained activated, but an increase in PDYN mRNA levels was also evident in the sensorimotor‐connected matrix compartment of the caudate. Neither self‐administration phase resulted in significant changes in the corresponding striatal regions of the low dose cocaine‐exposed primates. Moreover, cocaine self‐administration failed to alter the PDYN mRNA expression in high‐ or low‐expressing PDYN cell populations in the nucleus accumbens during any condition studied. These results demonstrate the vulnerability of the dorsal striatum (in particular the caudate) to neuroadaptations following long‐term high dose cocaine self‐administration. In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence.
Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen‐induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats
Authors: Lâm Thiên‐Trí , Leranth Csaba
Published: May 2003

Oestrogen is known to influence pyramidal cell spine synapse plasticity in the CA1 subfield of the hippocampus. Apart from direct oestrogen action on the hippocampus, oestrogen effects mediated by subcortical structures are known to be important. The purpose of this study was to investigate whether the medial septum diagonal band of Broca (MSDB) takes part in mediating oestrogen effects to the hippocampus. Special attention was given to the role of cholinergic MSDB neurons that project to the hippocampus, as a rather large population of them contains oestrogen receptors and, consequently, may be sensitive to oestrogen signals. Adult female rats were ovariectomized. Oestradiol‐ and cholesterol‐filled cannulae (control) were implanted into the MSDB. To selectively eliminate the cholinergic population of MSDB neurons of oestrogen‐treated animals, a group of rats was injected with 192 IgG‐saporin (SAP) into the lateral ventricle 1 week before the cannula implant. Immunostaining with anti‐choline acetyltransferase and parvalbumin (PA) showed that cholinergic but not PA‐containing GABAergic neurons were substantially reduced in the MSDB of SAP rats. Comparative electron microscopic unbiased stereological analysis on the spine synapse density of CA1 area pyramidal cells was performed between all animal groups. Rats that received oestradiol‐filled cannulae showed a higher (30%) spine synapse density than control animals. Oestrogen‐treated rats that had received SAP treatment showed no significant difference to controls. Thus, this observation indicates that septo‐hippocampal cholinergic neurons are involved in mediating oestrogen effects to the hippocampus. The relevance of this observation to mnemonic functions and Alzheimer's disease is discussed.
Cocaine‐induced psychomotor activity is associated with its ability to induce c‐fos mRNA expression in the subthalamic nucleus: effects of dose and repeated treatment
Authors: Uslaner Jason M. , Crombag Hans S. , Ferguson Susan M. , Robinson Terry E.
Published: May 2003

Factors that modulate the psychomotor activating effects of amphetamine and cocaine, such as environmental novelty and dose, also regulate the ability of these drugs to induce c‐fos mRNA expression in the subthalamic nucleus (STN). We hypothesized therefore that engagement of the STN may be important for stimulant‐induced psychomotor activation. To further test this hypothesis we examined whether repeated treatment with cocaine, which enhances its psychomotor activating effects (i.e. produces behavioural sensitization), also enhances its ability to induce c‐fos expression in the STN. In addition, given that STN activity is thought to be influenced by preproenkephalin mRNA‐containing (ENK+) neurons in the caudate–putamen, we also examined whether repeated cocaine treatment alters c‐fos expression in ENK+ cells. We report that: (i) cocaine pretreatment enhances the ability of a cocaine challenge to induce c‐fos mRNA expression in the STN, and this effect is most robust at challenge doses where behavioural sensitization is observed; (ii) the ability of cocaine to induce c‐fos in the STN is independent of the ability of cocaine to engage ENK+ cells. These results support the idea that the STN is involved in stimulant‐induced psychomotor activation and sensitization, but suggest that stimulant‐induced engagement of the STN is not dependent on ENK+ cells in the caudate–putamen. These findings may have implications concerning the neurobiological mechanisms underlying the behavioural effects of psychostimulant drugs.
D‐2‐hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats
Authors: Latini Alexandra , Scussiato Karina , Rosa Rafael Borba , Llesuy Susana , Belló‐Klein Adriane , Dutra‐Filho Carlos Severo , Wajner Moacir
Published: May 2003

Large amounts of d‐2‐hydroxyglutaric acid (DGA) accumulate in d‐2‐hydroxyglutaric aciduria (D‐2‐OHGA), an inherited neurometabolic disorder characterized by severe neurological dysfunction and cerebral atrophy. Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in this disease are virtually unknown. In this work, the in vitro effect of DGA on various parameters of oxidative stress was investigated; namely chemiluminescence, thiobarbituric acid‐reactive substances (TBA‐RS), total radical‐trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and the activities of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in cerebral cortex from 30‐day‐old‐rats. DGA significantly increased chemiluminescence and TBA‐RS and decreased TAR values in the cortical supernatants. In contrast, TRAP and the antioxidant enzyme activities were not altered by the metabolite. Furthermore, the DGA‐induced increase of TBA‐RS was fully prevented by the free radical scavengers ascorbic acid plus Trolox (water‐soluble α‐tocopherol) and attenuated by the inhibitor of nitric oxide synthase Nω‐nitro‐L‐arginine methyl ester (L‐NAME), suggesting the role of superoxide, hydroxyl and nitric oxide radicals in this action. The data indicate a stimulation of lipid peroxidation through the production of free radicals and a reduction of the brain capacity to efficiently modulate the damage associated with the enhanced generation of free radicals by DGA. In the case that these findings also occur in human D‐2‐OHGA, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this disease.
Insulin‐like growth factor‐I as a promoting factor for cerebellar Purkinje cell development
Authors: Fukudome Yuko , Tabata Toshihide , Miyoshi Tomoko , Haruki Shigeki , Araishi Kenji , Sawada Satsuki , Kano Masanobu
Published: May 2003

In the mammalian CNS, the peptide hormone insulin‐like growth factor‐I (IGF‐I) is synthesized in a certain subset of neurons and, it has been suggested, serves as a local neurotrophic factor. A postnatal increase in the expression of IGF‐I and the type‐1 IGF receptors (IGFR1) in the cerebellar cortex and its related brain regions indicates that developing cerebellar Purkinje cells (PC) may be an important target of IGF‐I. However, little is known about how IGF‐I influences PC development. Here we addressed this question, using a reduced environment of cerebellar neuron culture derived from perinatal mice. IGF‐I exogenously applied at a physiological concentration (10 nm) greatly promoted the dendritic growth and survival of the PCs. By contrast, IGF‐I only slightly promoted the somatic growth and little affected the maturation of the electrophysiological excitability of the PCs. The closely related hormone insulin had weaker promoting effects than did IGF‐I. IGF‐I appeared to at least bind to IGFR1 and to up‐regulate the signalling pathways involving the phosphoinositide 3‐kinase (PI3‐K), mitogen‐activated protein kinase (MAPK), p38 kinase (p38K), and an unknown signalling molecule(s). These signalling pathways may be coupled to the individual aspects of PC development in different manners and this may explain the difference in effects of IGF‐I among these aspects. These findings suggest that IGF‐I serves as a promoting factor for PC development, particularly postnatal survival and dendritic growth.
Alterations in the intrauterine environment by glucocorticoids modifies the developmental programme of the auditory system
Authors: Canlon Barbara , Erichsen Susan , Nemlander Elin , Chen Ming , Hossain Amzad , Celsi Gianni , Ceccatelli Sandra
Published: May 2003

Prenatal exposure to excessive glucocorticoids alters the programming of the metabolic and endocrine balance of various organs, including the nervous system. In the present study, prenatal glucocorticoid treatment was shown to increase the susceptibility of the inner ear to acoustic noise trauma in adult life. Acute auditory brainstem response thresholds were not different between the age‐matched groups. However, when measured at 48 h and 4 weeks postexposure, the dexamethasone (DEX)‐treated rats showed little or no recovery from the trauma. In contrast, normal rats showed a significant amount of recovery by 48 h postexposure and continued to show further recovery over 4 weeks. In addition, acoustic trauma resulted in a massive outer hair cell loss in the DEX rats compared to minor loss in the normal rats. To determine whether oxidative stress plays a role in the recovery phase of acoustic trauma, the free radical scavenger PBN (100 mg/kg) was administered before, during and several times after noise exposure. PBN treatment significantly reduced the physiological and morphological cochlear differences which were observed between DEX and control rats after acoustic trauma. These data support the hypothesis that alterations in the intrauterine environment may modify the developmental programme of the cochlea, inducing dysfunction later in adult life. Excessive prenatal exposure to dexamethasone decreased the potential for recovery of the cochlea to oxidative stress induced by acoustic trauma; this decreased recovery potential can be counteracted by treatment with antioxidants.
Glutamate motivational ensembles in nucleus accumbens: rostrocaudal shell gradients of fear and feeding
Authors: Reynolds Sheila M. , Berridge Kent C.
Published: May 2003

This study demonstrates that microinjection of an AMPA/kainate glutamate antagonist elicits motivated fear and feeding behaviour mapped along rostrocaudal gradients of positive‐to‐negative valence in nucleus accumbens shell (similar to rostrocaudal shell gradients recently reported for GABA agonist microinjections). Rats received rostral or caudal microinjections of the glutamate AMPA/kainate receptor antagonist DNQX (0, 50, 450 or 850 ng in 0.5 µL) or the NMDA receptor antagonist MK‐801 (0, 0.5, 1 or 2 µg in 0.5 µL), into medial accumbens shell prior to behavioural tests for fear, feeding or conditioning of place preference or avoidance. Another group received rostral or caudal microinjections of DNQX in nucleus accumbens core. Rostral shell DNQX microinjections potently increased appetitive food intake and established only weak conditioned place avoidance. Caudal shell DNQX microinjections elicited defensive treading behaviour, caused rats to defensively bite the experimenter and emit fearful distress vocalizations when handled, and established strong conditioned place avoidance. By contrast, no rostrocaudal gradients of motivational bivalence were produced by microinjections of the glutamate AMPA/kainate receptor antagonist DNQX into the core, or by microinjections of the NMDA antagonist MK‐801 into the shell. Our results indicate that appetitive and aversive motivation is carried in anatomically differentiated channels by mesocorticolimbic glutamate signals to microcircuits in the medial shell. Hyperpolarization of local shell ensembles by AMPA/kainate glutamate receptor blockade elicits fear and feeding behaviours mapped along distinct positive‐to‐negative rostrocaudal gradients.
Two distinct calcium‐sensitive and ‐insensitive PKC up‐ and down‐regulate an α‐bungarotoxin‐resistant nAChR1 in insect neurosecretory cells (DUM neurons)
Authors: Courjaret Raphaël , Grolleau Françoise , Lapied Bruno
Published: May 2003

While there is mounting knowledge about the structure and diversity of insect neuronal nicotinic acetylcholine receptors, less attention has been directed towards their intracellular regulation by calcium‐mediated activation or inhibition of protein phosphorylation. The main goal of this work was to delineate the chain of molecular events that lead to the up‐ and down‐regulation by two protein kinase Cs of an insect neuronal α‐bungarotoxin‐resistant nicotinic acetylcholine receptor (called nAChR1). The native nicotinic acetylcholine receptor intracellular regulation was studied on dissociated adult dorsal unpaired median neurons isolated from the terminal abdominal ganglion of the cockroach Periplaneta americana using whole‐cell patch‐clamp technique and calcium imaging. We report that under 0.5 µmα‐bungarotoxin treatment, the inward current produced by pressure ejection application of nicotine onto the cell body was differentially sensitive to specific protein kinase C activators and inhibitors. The phorbol ester PMA produced a calcium‐dependent increase in current amplitude blocked by chelerythrine. By contrast, the diacylglycerol analogue 1,2‐dioctanoyl‐sn‐glycerol produced a calcium‐independent reduction of the nicotinic response, reversed by rottlerin and chelerythrine. This indicated that two protein kinase C isozymes (‘classical’ and ‘novel’ protein kinase C, named PKC1 and PKC2, respectively) up‐ and down‐regulated nicotinic acetylcholine receptor function. PMA and 1,2‐dioctanoyl‐sn‐glycerol effects were mimicked by pirenzepine‐sensitive M1 muscarinic receptor subtype coupled to phospholipase C second messenger pathway. Low concentration of muscarine elevated internal calcium levels, which thereby activated PKC1. By contrast, a high concentration of muscarine strongly increased [Ca 2+]i, which induced inhibition of PKC1. This effect was reversed by FK506, suggesting the implication of PP2B which unmasked PKC2 activity mediating down‐regulation of nicotinic acetylcholine receptor.
Characterization of the human visual V6 complex by functional magnetic resonance imaging
Authors: Dechent Peter , Frahm Jens
Published: May 2003

Magnetoencephalography of a visual area along the human parieto‐occipital sulcus suggested that this region represents the human homologue of the monkey visual area V6 complex (visual area V6/visuomotor area V6A) involved in the integration of visual and somatomotor information. We used functional magnetic resonance imaging at 2.0 T and 2 × 2 × 3 mm3 resolution (16 sections) to characterize visual areas along the parieto‐occipital sulcus in five healthy human subjects. Paradigms comprised a full‐field checkerboard stimulation, a full‐field luminance flicker as well as a foveal and peripheral luminance flicker using both a direct and differential design for comparing functional states. Along the parieto‐occipital sulcus, and in contrast to primary visual areas, luminance stimulation evoked much larger activation volumes than checkerboard stimulation. Moreover, based on anatomic landmarks, luminance stimulation identified two functionally distinct regions of parieto‐occipital sulcus activations: an inferior part (supposedly visual area V6) and a superior portion (supposedly visuomotor area V6A). With these assignments, foveal vs. peripheral luminance stimulation revealed a weaker foveal overrepresentation in visual area V6/visuomotor area V6A than in early visual areas, and only a mild tendency for a retinotopic organization in visual area V6. Further analyses of the functional coding of the human visual area V6 complex require functional magnetic resonance imaging at even higher spatial resolution.
Neonatal administration of monosodium glutamate prevents the development of ethanol‐ but not psychostimulant‐induced sensitization: a putative role of the arcuate nucleus
Authors: Miquel Marta , Font Laura , Sanchis‐Segura Carles , Aragon Carlos M.G.
Published: May 2003

Lesions of the arcuate nucleus by monosodium glutamate, goldthioglucose and oestradiol valerate treatments are known to prevent the acute stimulating effect of ethanol in mice. On the basis of these results, the current study analysed whether a lesion of the arcuate nucleus by monosodium glutamate was able to block ethanol‐induced locomotor sensitization. To produce the arcuate nucleus lesions, pups were injected with saline or monosodium glutamate (4 mg/g body weight) subcutaneously on 5 alternate days, starting on postnatal day one. Sensitization treatments began 10 weeks after the initial lesions. Sensitization training consisted of six trials on alternate days, in which groups of mice were treated with ethanol (2 g/kg) or saline, and then tested in an open‐field for the induction of locomotor activity. The present study demonstrated that animals with monosodium glutamate‐induced lesions did not develop locomotor sensitization to ethanol. Different groups of mice were used to assay blood ethanol levels and to evaluate the effect of arcuate nucleus lesions on psychostimulant‐induced locomotor sensitization. Sensitization to cocaine or amphetamine was spared in monosodium glutamate‐pre‐treated animals, although the lesion of arcuate nucleus reduced the sensitivity of mice to cocaine. Our findings therefore suggest that the arcuate nucleus may be critical for the neuroadaptations that underlie the behavioural sensitization to ethanol, in contrast to those mediating psychostimulant‐induced sensitization.
Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis
Authors: Brown Jason , Cooper‐Kuhn Christiana M. , Kempermann Gerd , Van Praag Henriette , Winkler Jürgen , Gage Fred H. , Kuhn H. Georg
Published: May 2003

Exposure to an enriched environment and physical activity, such as voluntary running, increases neurogenesis of granule cells in the dentate gyrus of adult mice. These stimuli are also known to improve performance in hippocampus‐dependent learning tasks, but it is unclear whether their effects on neurogenesis are exclusive to the hippocampal formation. In this study, we housed adult mice under three conditions (enriched environment, voluntary wheel running and standard housing), and analysed proliferation in the lateral ventricle wall and granule cell neurogenesis in the olfactory bulb in comparison to the dentate gyrus. Using bromodeoxyuridine to label dividing cells, we could not detect any difference in the number of newly generated cells in the ventricle wall. When giving the new cells time to migrate and differentiate in the olfactory bulb, we observed no changes in the number of adult‐generated olfactory granule cells; however, voluntary running and enrichment produced a doubling in the amount of new hippocampal granule cells. The discrepancy between the olfactory bulb and the dentate gyrus suggests that these living conditions trigger locally through an as yet unidentified mechanism specific to neurogenic signals in the dentate gyrus.
Metabotropic glutamate receptor 5 (mGluR5)‐mediated phosphoinositide hydrolysis and NMDA‐potentiating effects are blunted in the striatum of aged rats: a possible additional mechanism in striatal senescence
Authors: Domenici Maria Rosaria , Pintor Annita , Potenza Rosa Luisa , Gaudi Simona , Grò Maria Cristina , Passarelli Francesca , Reggio Rosaria , Galluzzo Mariangela , Massotti Marino , Popoli Patrizia
Published: May 2003

The aim of the present work was to verify whether an impairment of subtype 5 metabotropic glutamate receptor‐mediated neurotransmission did occur in the aged striatum. To this end, the ability of the subtype 5 metabotropic glutamate receptor agonist, RS‐2‐chloro‐5‐hydroxyphenylglycine, to stimulate phosphoinositide hydrolysis and to potentiate N‐methyl‐d‐aspartate‐induced effects in striatal slices from young (3 months) and aged (24 months) rats was compared. The ability of RS‐2‐chloro‐5‐hydroxyphenylglycine to induce maximal phosphoinositide turnover and to potentiate N‐methyl‐d‐aspartate effects was significantly reduced in slices from old vs. young rats. These changes were associated with a significant reduction in the expression of subtype 5 metabotropic glutamate receptor protein (−28.8%) and phospholipase C‐β1 (−55.8%) in old striata, while receptor messenger ribonucleic acid expression was unchanged. These results show that the signalling associated with subtype 5 metabotropic glutamate receptors undergoes significant age‐related changes and that a reduced expression of subtype 5 metabotropic glutamate receptors and, more importantly, phospholipase C‐β1 may account for the functional decline of subtype 5 metabotropic glutamate receptors.
Differential effect of dopamine deficiency on the expression of NMDA receptor subunits in the weaver mouse brain
Authors: Fragioudaki K. , Kouvelas E. D. , Mitsacos A.
Published: May 2003

The weaver mutant mouse is characterized by degeneration of the dopaminergic mesencephalic neurons. The role of the dopaminergic system in the regulation of N‐methyl‐d‐aspartate (NMDA) receptor subunit expression was addressed in the present study. In situ hybridization experiments were conducted to determine the expression levels of the NMDA receptor subunit mRNAs, z1, ε1 and ε2, in striatum, nucleus accumbens, olfactory tubercle and cerebral cortical regions of 26‐day‐, 3‐ and 6‐month‐old weaver mice. Data indicated statistically significant increases in z1 and ε2 mRNA levels in 6‐month‐old weaver striatum, whereas at the same age ε1 mRNA expression was decreased in all striatal regions, as well as in the cortex. In the 26‐day‐old weaver striatum and nucleus accumbens, statistically significant increases were observed in ε1 mRNA levels, whereas no changes were observed in the other two subunits. In the somatosensory cortex of 26‐day‐old weaver brain an increased expression of all three subunits was observed. The upregulation of NMDA receptor subunit expression observed in the somatosensory cortex can be attributed to a decreased activity of the glutamatergic thalamocortical pathway, following the degeneration of the nigrostriatal dopaminergic fibres. In the striatum, the present results demonstrate a differential control on the expression of z1 and ε2 subunits on the one hand, and ε1 subunit on the other. It is suggested that dopamine exerts a negative control on the expression of z1 and ε2 subunits, through a downregulation of transcription factors associated with the AP1 regulatory site, which is mediated by the activation of striatal dopamine D2 receptors.
Diazepam‐induced changes on sleep and the EEG spectrum in mice: role of the α3‐GABAA receptor subtype
Authors: Kopp C. , Rudolph U. , Keist R. , Tobler I.
Published: May 2003

Benzodiazepines reduce EEG slow‐wave activity in non‐REM sleep by potentiating GABAergic neurotransmission at GABAA receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic system and synchronized by the inhibitory GABAergic neurons of the reticular thalamic nucleus. This region contains exclusively α3‐containing GABAA receptors. We investigated the role of these receptors in the mediation of diazepam effects on the sleep EEG by studying point‐mutated mice in which the α3‐GABAA receptor is diazepam‐insensitive [α3(H126R)]. Sleep was recorded for 12 h after i.p. injection of 3 mg/kg diazepam or vehicle at light onset in α3(H126R) and wild‐type controls (n = 13–17 per genotype). The main effect was a marked reduction of slow‐wave activity (EEG power density in 0.75–4.00 Hz) in non‐REM sleep and a concomitant increase in frequencies above 15.00 Hz in non‐REM sleep and waking in both genotypes. Neither effect of diazepam differed significantly between the genotypes. Despite the exclusive expression of α3‐containing GABAA receptors in the reticular thalamic nucleus, these receptors do not seem to be critical for the mediation of the effects of diazepam on the sleep EEG.
Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex and activation of apoptosis signal‐regulating kinase 1 during seizure‐induced neuronal death
Authors: Shinoda Sachiko , Skradski Shana L. , Araki Tomohiro , Schindler Clara K. , Meller Robert , Lan Jing‐Quan , Taki Waro , Simon Roger P. , Henshall David C.
Published: May 2003

The consequences of activation of tumour necrosis factor receptor 1 (TNFR1) during neuronal injury remain controversial. The apoptosis signal‐regulating kinase 1 (ASK1), a mitogen‐activated protein kinase kinase kinase, can mediate cell death downstream of TNFR1. Presently, we examined the formation of the TNFR1 signalling cascade and response of ASK1 during seizure‐induced neuronal death. Brief (40 min) seizures were induced in rats by intra‐amygdala microinjection of kainic acid, which elicited unilateral hippocampal CA3 neuronal death. Seizures caused a rapid decline in the expression of the silencer of death domains protein within injured CA3. Co‐immunoprecipitation analysis revealed a commensurate assembly of a TNFR1 scaffold complex containing TNFR‐associated death domain protein, receptor interacting protein and TNFR‐activating factor 2. In addition, recruitment of TNFR‐activating factor 2 was likely promoted by Bcl10‐mediated sequestering of cellular inhibitor of apoptosis protein 2. Apoptosis signal‐regulating kinase 1 was sequestered in a complex that contained the molecular chaperone 14‐3‐3β and protein phosphatase 5. Seizures triggered its dissociation, and the phosphorylation of the ASK1 substrates, mitogen‐activated protein kinase kinase 3/6 and 4. Subsequently, protein phosphatase 5 translocated into the nuclei of degenerating CA3 neurons, while ASK1 colocalized with the adaptor proteins Daxx and TNFR‐activating factor 2 at the outer membrane of injured CA3 neurons. Neutralizing antibodies to TNFα reduced the numbers of DNA damaged cells within the injured hippocampus. These data suggest ASK1 may be involved in the mechanism of seizure‐induced neuronal death downstream of a TNFR1 death‐signalling complex.
Reversible modulation of GABAA receptor‐mediated currents by light is dependent on the redox state of the receptor
Authors: Leszkiewicz Daniel N. , Aizenman Elias
Published: May 2003

Light has recently been shown to be a physical modulator of GABAA receptor activity. Here, we further characterize the effects of light on a native cortical and retinal population of GABAA receptors, and identify a possible mechanism for light induced potentiation using recombinant receptors. GABA‐induced currents in cortical neurons were observed to be rapidly and reversibly potentiated following exposure to a brief flash of light (0.5–2 s; > 280 nm) directed via an optical fibre (50 µm i.d.). GABAA receptor‐mediated responses in retinal ganglion cells were also enhanced by light, while glycine‐induced currents in these cells were unaffected by the same stimulus. We also determined that physiological levels of light, that is, those that would normally reach the retina, also enhanced GABA‐induced currents. Finally, we observed that chemical reduction of recombinant α1β2 and α1β2γ2S GABAA receptors by dithiothreitol substantially attenuated the effects of light. These results suggest that GABAA receptors can be reversibly modified by a brief pulse of light via an allosteric mechanism that is intimately linked to redox modulation.
Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins
Authors: Aronica Eleonora , Gorter Jan A. , Ijlst‐Keizers Helen , Rozemuller Annemieke J. , Yankaya Bulent , Leenstra Sieger , Troost Dirk
Published: May 2003

We examined the regulation of glutamate transporter protein expression after stimulation with selective metabotropic glutamate receptor (mGluR) agonists in cultured human glial cells. mGluR3 and mGluR5 are expressed in human astrocytes and in human glioma cells in vivo as well as in vitro, as shown by either RT‐PCR or western blot analysis. The selective group I agonist (S)‐3,5‐dihydroxyphenylglycine produced a significant down‐regulation of both GLAST and GLT‐1 protein expression in astrocytes cultured in the presence of growth factors. This condition mimics the morphology of reactive glial cells in vivo including an increased expression of mGluR5 protein (observed in pathological conditions). In contrast, (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine, a selective agonist of group II metabotropic glutamate receptors, positively modulates the expression of GLAST and GLT‐1 proteins. A similar opposite effect of (S)‐3,5‐dihydroxyphenylglycine and (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine was observed for the expression of EAAT3 protein in U373 glioblastoma cell line. Selective group I and II antagonists prevented these effects. Pharmacological inhibition of mitogen‐activated protein kinase and phosphatidylinositol‐3‐K pathways reduces the induction of GLT‐1 observed in response to the group II metabotropic glutamate receptor agonist (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine. Thus, mGluR3 and mGluR5 can critically and differentially modulate the expression of glutamate transporters and may represent interesting pharmacological targets to regulate the extracellular levels of glutamate in pathological conditions.