bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous regeneration of severed optic axons restores mapped visual responses to the adult rat superior colliculus
Authors: Foerster Anne P. , Holmes Michael J. 
Published: March 2003

AbstractTo test whether a spontaneous and functional regeneration of severed axons could occur within the adult mammalian central nervous system, a long‐term recovery of microelectrode‐mapped visual response was sought in the superior colliculus (SC) after its total or near‐total abolition by a precise guillotine cut of the retinocollicular pathway. Recoveries were found 3 weeks or later in 15 of the 36 animals studied; in 10 of these recoveries, half or more of the width of the SC was involved. The recovered responses were often activated from within a normally small area of the visual field. Appropriate retinotopic maps were restored. Intraocular horseradish peroxidase tracing revealed a variety of novel optic trajectories, passing around lesions even of totally cut pathways, which eventually terminated in normally retinorecipient layers of those recovered SCs. Such detours could not be explained by a mechanical reorientation of brain structures. When exactly comparable lesions were examined within a few days, there were no detours: severed optic axons faced the cuts. In long‐term animals where responsiveness remained absent, optic axonal reorientations were observed near lesions but the SC was not innervated. Extensive long‐term recoveries were in marked contrast to the occasional rapid ones, found within a few days postlesion, which involved only an outermost silenced border of SC. These were attributed to a rapid reversal of conduction failure in spared, bordering, axons of this topographically organized pathway. The findings support the conclusion that, after they are cut, numbers of optic axons can regenerate to the SC and restore appropriate circuitry therein.
Withdrawal from repeated amphetamine administration reduces NMDAR1 expression in the rat substantia nigra, nucleus accumbens and medial prefrontal cortex
Authors: Lu Wenxiao , Monteggia Lisa M. , Wolf Marina E. 
Published: March 2003

AbstractGlutamate plays a critical role in neuroadaptations induced by drugs of abuse. This study determined whether expression of the NMDAR1 subunit of the NMDA receptor is altered by repeated amphetamine administration. We quantified NMDAR1 mRNA (using in situ hybridization with 35S‐labelled oligonucleotide probes) and immunolabelling (using immunocytochemistry with 35S‐labelled secondary antibodies) in rat ventral midbrain, nucleus accumbens and prefrontal cortex after 3 or 14 days of withdrawal from five daily injections of saline or amphetamine sulphate (5 mg/kg/day). No changes in NMDAR1 expression were observed after 3 days of withdrawal, whereas significant decreases were observed in all regions after 14 days. NMDAR1 mRNA levels in midbrain were too low for reliable quantification, but immunolabelling was decreased significantly in intermediate and caudal portions of the substantia nigra. This may indicate a reduction in excitatory drive to substantia nigra dopaminergic neurons. In the nucleus accumbens, there were significant decreases in NMDAR1 mRNA levels (74.8 ± 7.7% of control, P < 0.05) and immunolabelling (76.7 ± 4.4%, P < 0.05). This may account for previously‐reported decreases in the electrophysiological responsiveness of nucleus accumbens neurons to NMDA after chronic amphetamine treatment, and contribute to dysregulation of goal‐directed behaviour. In prefrontal cortex, there was a significant decrease in NMDAR1 mRNA levels (76.1 ± 7.1%, P < 0.05) and a trend towards decreased immunolabelling (89.5 ± 7.0%). This may indicate decreased neuronal excitability within prefrontal cortex. A resultant decrease in activity of excitatory prefrontal cortical projections to nucleus accumbens or midbrain could synergize with local decreases in NMDAR1 to further reduce neuronal excitability in these latter regions.
Effects of nerve growth factor on visual cortical plasticity require afferent electrical activity
Authors: Caleo Matteo , Lodovichi Claudia , Maffei Lamberto 
Published: March 2003

AbstractIt is known that administration of nerve growth factor (NGF) prevents the ocular dominance shift induced by monocular deprivation in the rat. To determine whether electrical activity in the visual afferent pathway is required for NGF effects on ocular dominance, we infused NGF into the cortex of animals subjected to complete monocular blockade of retinal discharges. Rats at the peak of the critical period received intravitreal tetrodotoxin (TTX) injections to silence activity in one eye for a period of 6–7 days; NGF was concurrently delivered into the visual cortex by means of osmotic minipumps. At the end of the treatment period, the ocular dominance distribution of cortical neurons was assessed by single‐cell recordings. The results demonstrate that while infusion of NGF is effective in preventing the ocular dominance shift in lid‐sutured rats, virtually no rescue can be observed in TTX‐injected animals. Identical results were obtained when a specific agonist of the NGF receptor TrkA, the bivalent anti‐rat TrkA IgG (RTA), was infused into the cortex in place of NGF. We conclude that NGF signalling via the TrkA receptor must be coupled to afferent electrical activity to produce its effects on the eye preference of cortical neurons. This suggests a generalized mechanism in which high‐affinity neurotrophin receptor activation and afferent discharge interact to modulate neuronal plasticity in the developing visual cortex.
Re‐examination of the human taste region: a positron emission tomography study
Authors: Frey S. , Petrides M. 
Published: March 2003

AbstractThere is considerable uncertainty regarding the cortical areas in the human brain that are involved in gustatory processing. Evidence from nonhuman primates indicates that parts of the peri‐central opercular region (secondary somatosensory cortex) and insular cortex may be important for gustatory processing. The aim of the study was to examine changes in cerebral blood flow during gustatory stimulation (with sucrose or water) in the insulo‐opercular region of the human brain with positron emission tomography using only movement of the tongue and mouth as control conditions. This is important because subtractions of responses to one gustatory stimulus from those to another may mask gustatory activity that is common to both stimuli, even when the control stimulus is an apparently tasteless one (e.g. water). Bilateral increases in activity were observed in the insulo‐opercular region and, consistent with animal work, they indicate that there are a number of separate foci within this general area where primary gustatory inputs may be processed.
NGFI‐A gene expression induced in the rat suprachiasmatic nucleus by photic stimulation: spread into hypothalamic periventricular somatostatin neurons and GABA receptor involvement
Authors: Tanaka Masaki , Iijima Norio , Amaya Fumimasa , Tamada Yoshitaka , Ibata Yasuhiko 
Published: March 2003

AbstractWe studied NGFI‐A gene expression in response to photic stimulation in the rat suprachiasmatic nucleus (SCN) using in situ hybridization histochemistry. This gene expression spread within the SCN and extended dorsally into the anterior hypothalamus after 30 min–1 h of light exposure at circadian time (CT) CT18. It appeared first in the ventrolateral SCN where the retinohypothalamic tract (RHT) innervates, then it expanded dorsomedially in the SCN and beyond the SCN to the anterior hypothalamus. However, stimulation for 2 h light exposure decreased its expression in the SCN. NGFI‐A expression in the somatostatin neurons in the periventricular nucleus increased from 8.7% to 41% with increasing exposure time from 5 to 30 min. NGFI‐A mRNA expression in the SCN was suppressed by pretreatment with baclofen, the GABAB receptor agonist. The spread of photic information from the retina to the SCN was visualized at immediate early gene level not only in the SCN but also in the area beyond the SCN. Somatostatin neurons in the periventricular nucleus which project to the external layer of the median eminence and are involved in regulation of growth hormone release showed NGFI‐A gene expression corresponding to the duration of photic stimulation. Photic‐induced NGFI‐A gene expression in the SCN was also shown to be regulated by GABAergic transmission via GABAB receptors. These NGFI‐A gene‐expressing cells in the SCN may be involved in the circadian entrainment by light and some of those outside the SCN may participate in the regulation of neuroendocrine function.
Knowing which and knowing what: a potential mouse model for age‐related human declarative memory decline
Authors: Marighetto Aline , Etchamendy Nicole , Touzani Khalid , Torrea Cedric Cortes , Yee Benjamin K. , Rawlins John Nicholas P. , Jaffard Robert 
Published: March 2003

AbstractThe present study was built on the original report of Eichenbaum et al. [Eichenbaum, H., Fagan, A., Mathews, P. & Cohen, N.J. (1988), Behav. Neurosci., 102, 3531–3542] on the contrasting effects of fornix lesion in different versions of an odour‐guided discrimination task in rats, and attempted to extend this into a mouse model for the preferential loss of declarative memory seen in human senescence. Each of the two experiments reported here consisted of a two‐stage paradigm, with an initial learning phase followed by a test phase. The information acquired in the first stage was identical in both experiments, i.e. the valence or reward contingency associated with six (three positive and three negative) arms of a radial maze. The only parameter which was varied between Experiment A and B, and also between the two successive stages within each experiment, was the way of presenting the arms to the mice, i.e. either in pairs (simultaneous discriminations) or one at a time (successive go : no‐go discrimination). Performance in the first stage demonstrated that our aged mice were impaired in learning concurrent simultaneous discriminations but not successive go/no‐go discrimination, thereby resembling that reported in rats with hippocampal damage. Most importantly, our present set of data supports the conclusion that two forms of memory expression for the same piece of acquired experience can be assessed in the same subjects by manipulating the way of presenting two arms that were previously experienced separately. These two forms of memory expressions are differentially affected in aged mice, thereby demonstrating the highly selective and specific deleterious effect of ageing.
Novelty causes time‐dependent retrograde amnesia for one‐trial avoidance in rats through NMDA receptor‐ and CaMKII‐dependent mechanisms in the hippocampus
Authors: Izquierdo I. , Schröder N. , Netto C. A. , Medina J. H. 
Published: March 2003

AbstractExposure to a novel environment (an open field) for 2 min, 1 h after one‐trial inhibitory avoidance training, hindered memory of the avoidance task measured 24 h later. The effect was seen regardless of the intensity of the avoidance training footshock. The effect was not seen if the exposure to novelty was carried out 5 min before, or 6 h after, the avoidance training, or if the animals did not perceive the open field as new and react accordingly. The amnesic effect of the novelty presented 1 h after avoidance training was blocked by the intrahippocampal infusion of d‐2‐amino‐5‐phosphono‐pentanoic acid (AP5, 25 nmoles per side) or 1‐(N,O‐bis‐[5‐isoquinolinylsulphonyl]‐N‐methyl‐l‐tyrosyl)‐4‐phenylpiperazine (KN62, 100 μmoles per side) but not by that of C32H25N3O6 (KT5720, 90 μmoles per side) given 5 min before the novelty. In the open field there was habituation, measured by the decrease in exploration between the first and second minute. AP5 and KN62 impaired this habituation, but not KT5720. Exploration of the open field was similar in the groups exposed to the avoidance task 5 min later, or 1 h or 6 h before. Therefore, there was no reciprocity between the effect of the two tasks: novelty was amnesic for the one‐trial avoidance task, but the opposite was not true. The amnesic effect of novelty appears to rely on N‐methyl‐d‐aspartate (NMDA) receptor‐ and calcium/calmodulin‐dependent protein kinase II (CaMKII)‐dependent, but not on PKA‐dependent, aspects of its habituation learning.
Cyclosporin A and its nonimmunosuppressive analogue N‐Me‐Val‐4‐cyclosporin A mitigate glucose/oxygen deprivation‐induced damage to rat cultured hippocampal neurons
Authors: Khaspekov Leonid , Friberg Hans , Halestrap Andrew , Viktorov Ilja , Wieloch Tadeusz 
Published: March 2003

AbstractWhen mouse hippocampal neuronal cultures, 2–3 weeks in vitro, were transiently exposed to combined glucose and oxygen deprivation (100% argon, 5% CO2, in glucose‐free medium) for 90 min, extensive neuronal degeneration had occurred after 24 h of reoxygenation. When these cultures were preincubated with cyclosporin A, a calcineurin inhibitor and a blocker of the mitochondrial permeability transition, neuronal death diminished by 30–50%. Similarly, the cyclosporin A analogue, N‐Me‐Val‐4‐cyclosporin A, a potent blocker of the mitochondrial permeability transition with no significant calcineurin blocking activity, decreased cell death by 70–80%. Both cyclosporin A and N‐Me‐Val‐4‐cyclosporin A markedly attenuated calcium‐induced swelling of isolated mouse brain mitochondria by blocking the mitochondrial permeability transition. The potassium thiocyanate‐stabilized binding of cyclophilin D to mouse brain mitochondrial membranes was completely prevented by cyclosporin A and N‐Me‐Val‐4‐cyclosporin A. Our results strongly suggest that the mitochondrial permeability transition is involved in oxygen/glucose deprivation‐induced cell death in vitro. Cyclophilin D and other components of the mitochondrial permeability transition may be important targets for neuroprotective and anti‐ischaemic drugs.
Multiple trophic actions of heparin‐binding epidermal growth factor (HB‐EGF) in the central nervous system
Authors: Kornblum Harley I. , Zurcher Shelley D. , Werb Zena , Derynck Rik , Seroogy Kim B. 
Published: March 2003

AbstractThe epidermal growth factor (EGF) family of ligands interacts with the epidermal growth factor receptor (EGF‐R) to produce numerous direct and indirect actions on central nervous system cells. They induce the proliferation of astrocytes and multipotent progenitors (‘stem’ cells) and promote the survival and differentiation of postmitotic neurons. Heparin‐binding epidermal growth factor (HB‐EGF) interacts with both EGF‐R and a related receptor, ErbB4, whereas transforming growth factor alpha (TGFα) interacts only with EGF‐R. Because of the unique characteristics of HB‐EGF and the potential utility of EGF family members in brain repair, we examine the effects of HB‐EGF on rat and mouse CNS cells in vitro and compare them to those of TGFα. We find that, like TGFα, HB‐EGF stimulates the proliferation of CNS astrocytes and multipotent progenitors. These proliferative effects require the expression of EGF‐R, as no such effects are observed in cells derived from EGF‐R–/– mice. Both HB‐EGF and TGFα enhanced the survival of neurons derived from the neocortex and the striatum. Within these neuron‐enriched cultures, nestin‐positive cells but not neurons express EGF‐R mRNA, indicating that the neurotrophic actions of EGF‐R ligands are a result of indirect stimulation mediated by non‐neuronal cells. The neurotrophic actions of HB‐EGF and TGFα are accompanied by an elevation in immunoreactive dual phosphorylated mitogen‐activated protein kinase (MAP kinase) in neurons, providing evidence that the MAP kinase cascade mediates these actions. In situ hybridization studies demonstrate that HB‐EGF mRNA is present within the brainstem as early as E14 and subsequently is found in the developing cortical plate, hippocampus, cerebellar Purkinje cells and ventrobasal thalamus, among other brain areas. These findings indicate that HB‐EGF may be an important trophic factor in the developing CNS and is a useful candidate molecule for brain repair strategies.
Pyruvate and lactate protect striatal neurons against N‐methyl‐d‐aspartate‐induced neurotoxicity
Authors: Maus Marion , Marin Philippe , Israël Maurice , Glowinski Jacques , Prémont Joël 
Published: March 2003

AbstractA sustained release of glutamate contributes to neuronal loss during cerebral ischaemia. Using cultured mouse striatal neurons, we observed that glucose deprivation, which occurs in this pathological process, enhanced the N‐Methyl‐d‐aspartate (NMDA)‐ or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)‐induced neurotoxicity. The end products of glycolysis, lactate and pyruvate, strongly protected neurons from these neurotoxic effects. The neuroprotective effect of pyruvate (which is more prominent in the absence of glucose) was not related to its ability to react with H2O2 by a decarboxylation process. Pyruvate and l‐lactate strongly counteracted the deep decrease in the neuronal ATP content induced by NMDA, indicating that they might protect striatal neurons by rescuing cellular energy charge. Addition of MK‐801 after the NMDA withdrawal completely protected neurons, suggesting that NMDA neurotoxicity resulted from a delayed NMDA receptor activation probably linked to a delayed release of an endogenous agonist in the extracellular medium. The strong accumulation of extracellular glutamate which was found in both sham and NMDA‐treated cultures was markedly decreased by pyruvate. Thus, pyruvate might also exert its protecting activity by decreasing the delayed accumulation of glutamate which seemed to be neurotoxic only after a preexposure of neurons to NMDA.
Seasonal regulation of food intake and body weight in the male Siberian hamster: studies of hypothalamic orexin (hypocretin), neuropeptide Y (NPY) andpro‐opiomelanocortin (POMC)
Authors: Reddy Akhilesh B. , Cronin Anna S. , Ford Hazel , Ebling Francis J. P. 
Published: March 2003

AbstractThe aim of these experiments was to investigate the relationship between hypothalamic expression of orexin (also called hypocretin), neuropeptide Y (NPY) and pro‐opiomelanocortin (POMC) mRNA and seasonal cycles of body weight and food intake in the Siberian hamster. Adult males were transferred from long days of 16 h light and 8 h dark to short days of 8 h light and 16 h dark, a procedure known to induce major reductions in food intake and body weight in this species. After 8 weeks of exposure to short days, while body weight was declining, hypothalamic NPY mRNA levels as assessed by in situ hybridization were slightly lower (P < 0.05) than in age‐matched controls exposed to long days. After 12 weeks with short days, when body weight would be expected to have reached its seasonal nadir, POMC mRNA levels were lower (P < 0.05) than in hamsters under long days. At no stage did orexin mRNA levels in hamsters under short days differ significantly from levels in those under long days. To investigate further the role of these peptide systems in seasonal changes in body weight and food intake, two provocative tests were carried out. Firstly, a 48‐h fast induced a significant increase (P < 0.025) in hypothalamic NPY mRNA levels in both long‐ and short‐day conditions, but did not change hypothalamic POMC or orexin mRNA levels. Secondly, systemic (intraperitoneal) treatment with recombinant murine leptin (5 mg/kg body weight) significantly decreased (P < 0.01) food intake over a 6‐h post‐treatment period in both long‐ and short‐day conditions. However, this acute leptin treatment did not induce significant changes in hypothalamic orexin, NPY or POMC mRNA abundance. The increase in NPY expression in both long‐ and short‐day conditions following food restriction and the suppression of food intake by leptin in both conditions suggests that acute homeostatic mechanisms operate in both long‐day (obese) and short‐day (nonobese) conditions. The lack of major changes in orexin, NPY and POMC in such different metabolic states suggest that other central systems must play a greater role in generating these states. Such findings are consistent with the ‘sliding set‐point’ hypothesis, that is, seasonal cycles in food intake and fat metabolism are brought about by as yet unknown central mechanisms that chronically alter the level (‘set point’) around which homeostasis occurs, rather than resulting from changes in the potency of the acute feedback mechanisms themselves.
Repetitive transcranial magnetic stimulation in rats: evidence for a neuroprotective effect in vitro and in vivo
Authors: Post Anke , Müller Marianne B. , Engelmann Mario , Keck Martin E. 
Published: March 2003

AbstractIn recent years, repetitive transcranial magnetic stimulation (rTMS) of the human brain has been used as a therapeutic tool in a variety of psychiatric and neurological disorders. However, to understand the mechanisms underlying any potential therapeutic effects, and possible adverse effects, studies are necessary on how magnetic stimuli induced by rTMS interact with central nervous system (CNS) regulation. In the current study, we failed to find cognitive impairments or structural alterations in rat brains after 11 weeks of long‐term treatment with rTMS, which if present would indicate neuronal damage. In contrast, our in vitro studies showed that magnetic stimulation analogous to rTMS increased the overall viability of mouse monoclonal hippocampal HT22 cells and had a neuroprotective effect against oxidative stressors, e.g. amyloid beta (Aβ) and glutamate. The treatment increased the release of secreted amyloid precursor protein (sAPP) into the supernatant of HT22 cells and into cerebrospinal fluid from rats. HT22 cells preincubated with cerebrospinal fluid from rTMS‐treated rats were found to be protected against Aβ. These findings suggest that neurochemical effects induced by rTMS do not lead to reduced neuronal viability, and may even reduce the detrimental effects of oxidative stress in neurons.
Mitral cell loss following lateral olfactory tract transection increases proliferation density in rat olfactory epithelium
Authors: Weiler Elke , Farbman Albert I. 
Published: March 2003

AbstractOlfactory sensory neurons are replaced throughout the life of vertebrates by proliferation of basal cells and differentiation of the new cells into neurons. Removal of their target, the olfactory bulb, increases proliferation twofold because sensory neurons die prematurely, suggesting that the olfactory bulb provides a trophic substance required for survival. We asked whether mitral cells, a major postsynaptic target of olfactory sensory neurons, are involved in their survival. We report here that depletion of mitral cells increases proliferation and cell death in the olfactory sensory neuron population. Mitral cell loss was induced unilaterally by transection of their axons in the lateral olfactory tract in 18‐day‐old rats. At all time points after surgery (3 weeks, 7 weeks, 3 months, 14 months) there was a 29% mean reduction in the number of mitral cells ipsilateral to the transection. The surviving mitral cells were smaller than controls and had less rough endoplasmic reticulum. In the olfactory epithelium, proliferation density (BrdU‐positive cells/mm epithelial length) in the progenitor basal cells was increased by an average of 20–25% at all time points, as was the number of TUNEL‐positive dying cells. The results are consistent with the notion that mitral cells, or the synaptic sites on them, are a source of trophic factor required for maintenance of the lives of olfactory sensory cells. The target field of postsynaptic neurons remaining after lateral olfactory tract transection is insufficient to maintain normal survival of all existing olfactory neurons. In unperturbed animals the proliferation density declines in an age‐dependent manner and interestingly the decline on the tractotomized side is parallel. This suggests that with age the sensory cells are less dependent on their targets.