bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glial fibrillary acidic protein gene promoter is differently modulated by transforming growth factor‐beta 1 in astrocytes from distinct brain regions
Authors: De Oliveira Sousa Vivian , Romão Luciana , Neto Vivaldo Moura , Gomes Flávia Carvalho Alcantara 
Published: April 2004

AbstractThe expression of glial fibrillary acidic protein (GFAP), the major intermediate filament protein of mature astrocytes, is regulated under developmental and pathological conditions. Recently, we have investigated GFAP gene modulation by using a transgenic mouse bearing part of the GFAP gene promoter linked to the β‐galactosidase reporter gene. We demonstrated that cerebral cortex neurons activate the GFAP gene promoter, inducing transforming growth factor‐beta 1 (TGF‐β1) secretion by astrocytes. Here, we report that cortical neurons or conditioned medium derived from them do not activate the GFAP gene promoter of transgenic astrocytes derived from midbrain and cerebellum suggesting a neuroanatomical regional specificity of this phenomenon. Surprisingly, they do induce synthesis of TGF‐β1 by these cells. Western blot and immunocytochemistry assays revealed wild distribution of TGF receptor in all subpopulations of astrocytes and expression of TGF‐β1 in neurons derived from all regions, thus indicating that the unresponsiveness of the cerebellar and midbrain GFAP gene to TGF‐β1 is not due to a defect in TGF‐β1 signalling. Together, our data highlight the great complexity of neuron–glia interactions and might suggest a distinct mechanism underlying modulation of the GFAP gene in the heterogeneous population of astrocytes throughout the central nervous system.
Anxiety and cognition in histamine H3 receptor−/− mice
Authors: Rizk Angela , Curley Justine , Robertson Jennifer , Raber Jacob 
Published: April 2004

AbstractHistamine H3 receptors (H3Rs) were first characterized as autoreceptors modulating histamine release and synthesis via negative feedback. Acute H3R stimulation or blockade with selective agonists and antagonists suggests a role for H3R in anxiety and cognition. However, little is known about the long‐term effects of H3R blockade on brain function. In the current study, mice lacking H3 receptors (H3R−/−) were used to investigate the role of H3R‐mediated signalling in anxiety and cognition. H3R−/− mice showed enhanced spatial learning and memory in the Barnes maze. In addition, H3R−/− mice showed reduced measures of anxiety in the elevated plus and zero mazes involving exploratory behaviour and avoidable anxiety‐provoking stimuli, but enhanced acoustic startle responses involving unavoidable anxiety‐provoking stimuli. These behavioural alterations were associated with higher arginine vasopressin levels in the central and basolateral nuclei of the amygdala. These findings support a role for H3Rs in mediating histamine effects on spatial learning and memory and measures of anxiety.
Characterization of the inhibitory glycine receptor on entorhinal cortex neurons
Authors: Breustedt Jörg , Schmitz Dietmar , Heinemann Uwe , Schmieden Volker 
Published: April 2004

AbstractIn addition to the well‐established functional description of the glycine receptor (GlyR) in the spinal cord, GlyR expression has recently been found in higher brain regions, such as the striatum or hippocampus. In this study we have investigated the electrophysiological response of glycine in the rat entorhinal cortex slice. In all recorded cells we found significant current responses to glycine with an EC50 value of about 100 µm. Most importantly, we detected a cross‐inhibition of glycine responses by GABA but not vice versa. These findings are in line with recent published data of cross‐talks between GABAAR and GlyR but indicate a novel type of cross‐inhibition of these receptors in the entorhinal cortex.
Differential regulation of hippocampal progenitor proliferation by opioid receptor antagonists in running and non‐running spontaneously hypertensive rats
Authors: Persson Anders I. , Naylor Andrew S. , Jonsdottir Ingibjörg H. , Nyberg Fred , Eriksson Peter S. , Thorlin Thorleif 
Published: April 2004

AbstractVoluntary running in mice and forced treadmill running in rats have been shown to increase the amount of proliferating cells in the hippocampus. Little is known as yet about the mechanisms involved in these processes. It is well known that the endogenous opioid system is affected during running and other forms of physical exercise. In this study, we evaluated the involvement of the endogenous opioids in the regulation of hippocampal proliferation in non‐running and voluntary running rats. Nine days of wheel running was compared with non‐running in spontaneously hypertensive rats (SHR), a rat strain known to run voluntarily. On the last 2 days of the experimental period all rats received two daily injections of the opioid receptor antagonists naltrexone or naltrindole together with injections of bromodeoxyuridine to label dividing cells. Brain sections from the running rats showed approximately a five‐fold increase in newly generated cells in the hippocampus, and this increase was partly reduced by naltrexone but not by naltrindole. By contrast, both naltrexone and naltrindole increased hippocampal proliferation in non‐running rats. In non‐running rats the administration of naltrexone decreased corticosterone levels and adrenal gland weights, whereas no significant effects on these parameters could be detected for naltrindole. However, adrenal gland weights were increased in naltrexone‐ but not in naltrindole‐administered running rats. In addition, in voluntary running rats there was a three‐fold increase in the hippocampal levels of Met‐enkephalin‐Arg‐Phe compared with non‐runners, indicating an increase in opioid activity in the hippocampus during running. These data suggest an involvement of endogenous opioids in the regulation of hippocampal proliferation in non‐running rats, probably through hypothalamic–pituitary–adrenal axis modulation. During voluntary running in SHR naltrexone altered hippocampal proliferation via as yet unknown mechanisms.
Automatic detection of motion direction changes in the human brain
Authors: Pazo‐Alvarez P. , Amenedo E. , Cadaveira F. 
Published: April 2004

AbstractThe possibility that the visual system is able to register unattended changes is still debated in the literature. However, it is difficult to understand how a sensory system becomes aware of unexpected salient changes in the environment if attention is required for detecting them. The ability to automatically detect unusual changes in the sensory environment is an adaptive function which has been confirmed in other sensory modalities (i.e. audition). This deviance detector mechanism has proven to be based on a preattentive nonrefractory memory‐comparison process. To investigate whether such automatic change detection mechanism exists in the human visual system, we recorded event‐related potentials to sudden changes in a biologically important feature, motion direction. Unattended sinusoidal gratings varying in motion direction in the peripheral field were presented while subjects performed a central task with two levels of difficulty. We found a larger negative displacement in the electrophysiological response elicited by less frequent stimuli (deviant) at posterior scalp locations. Within the latency range of the visual evoked component N2, this differential response was elicited independently of the direction of motion and processing load. Moreover, the results showed that the negativity elicited by deviants was not related to a differential refractory state between the electrophysiological responses to frequent and infrequent directions of motion, and that it was restricted to scalp locations related to motion processing areas. The present results suggest that a change‐detection mechanism sensitive to unattended changes in motion direction may exist in the human visual system.
Temporal and spatial expression patterns of canonical clock genes and clock‐controlled genes in the suprachiasmatic nucleus
Authors: Hamada Toshiyuki , Antle Michael C. , Silver Rae 
Published: April 2004

AbstractIn mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus control endogenous circadian rhythms and entrainment to the environment. A core SCN region of calbindin (CalB)‐containing cells is retinorecipient and the cells therein lack rhythmic expression of clock genes and electrical activity. The core is surrounded by a ‘shell’ of rhythmic oscillator cells. In the present experiments, we studied the spatial arrangement of oscillator cells by examining the spatial and temporal patterns of expression of the canonical clock genes Per1, Per2 and vasopressin mRNA, a clock‐controlled gene. Surprisingly, in the SCN shell, the dorsomedial cells were the first to rhythmically express both Per1 and VP mRNA, with gene expression then spreading very slowly through much of the nucleus for the next 12 h then receding to baseline levels. Following a light pulse, Per expression increased after 1 h in the core SCN and after 1.5 h in the shell. Although expression in the shell occurred earlier in light‐pulsed animals than in those housed in constant darkness, it still followed the same spatial and temporal expression pattern as was observed in constant darkness. The results suggest that not only is the SCN organized into light‐responsive and rhythmic regions but also that the rhythmic region of the SCN itself has an ordered arrangement of SCN oscillator cells.
Stereological analysis of the reorganization of the dentate gyrus following entorhinal cortex lesion in mice
Authors: Phinney A. L. , Calhoun M. E. , Woods A. G. , Deller T. , Jucker M. 
Published: April 2004

AbstractDenervation of the dentate gyrus by entorhinal cortex lesion has been widely used to study the reorganization of neuronal circuits following central nervous system lesion. Expansion of the non‐denervated inner molecular layer (commissural/associational zone) of the dentate gyrus and increased acetylcholinesterase‐positive fibre density in the denervated outer molecular layer have commonly been regarded as markers for sprouting following entorhinal cortex lesion. However, because this lesion extensively denervates the outer molecular layer and causes tissue shrinkage, stereological analysis is required for an accurate evaluation of sprouting. To this end we have performed unilateral entorhinal cortex lesions in adult C57BL/6J mice and have assessed atrophy and sprouting in the dentate gyrus using modern unbiased stereological techniques. Results revealed the expected increases in commissural/associational zone width and density of acetylcholinesterase‐positive fibres on single brain sections. Yet, stereological analysis failed to demonstrate concomitant increases in layer volume or total acetylcholinesterase‐positive fibre length. Interestingly, calretinin‐positive fibres did grow beyond the border of the commissural/associational zone into the denervated layer and were regarded as sprouting axons. Thus, our data suggest that in C57BL/6J mice shrinkage of the hippocampus rather than growth of fibres underlies the two morphological phenomena most often cited as evidence of regenerative sprouting following entorhinal cortex lesion. Moreover, our data suggest that regenerative axonal sprouting in the mouse dentate gyrus following entorhinal cortex lesion may be best assessed at the single‐fibre level.
Co‐localization of endomorphin‐2 and substance P in primary afferent nociceptors and effects of injury: a light and electron microscopic study in the rat
Authors: Sanderson Nydahl Katarina , Skinner Kate , Julius David , Basbaum Allan I. 
Published: April 2004

AbstractEndomorphin‐2 (EM2) is a tetrapeptide with remarkable affinity and selectivity for the mu‐opioid receptor. In the present study, we used double‐fluorescence and electron microscopic immunocytochemistry to identify subsets of EM2‐expressing neurons in dorsal root ganglia and spinal cord dorsal horn of adult rats. Within the lumbar dorsal root ganglia, we found EM2 immunoreactivity mainly in small‐to‐medium size neurons, most of which co‐expressed the neuropeptide substance P (SP). In adult rat L4 dorsal root ganglia, 23.9% of neuronal profiles contained EM2 immunoreactivity and ranged in size from 15 to 36 µm in diameter (mean 24.3 ± 4.3 µm). Double‐labelling experiments with cytochemical markers of dorsal root ganglia neurons showed that approximately 95% of EM2‐immunoreactive cell bodies also label with SP antisera, 83% co‐express vanilloid receptor subtype 1/capsaicin receptor, and 17% label with isolectin B4, a marker of non‐peptide nociceptors. Importantly, EM2 immunostaining persisted in mice with a deletion of the preprotachykinin‐A gene that encodes SP. In the lumbar spinal cord dorsal horn, EM2 expression was concentrated in presumptive primary afferent terminals in laminae I and outer II. At the ultrastructural level, electron microscopic double‐labelling showed co‐localization of EM2 and SP in dense core vesicles of lumbar superficial dorsal horn synaptic terminals. Finally, 2 weeks after sciatic nerve axotomy we observed a greater than 50% reduction in EM2 immunoreactivity in the superficial dorsal horn. We suggest that the very strong anatomical relationship between primary afferent nociceptors that express SP and EM2 underlies an EM2 regulation of SP release via mu‐opioid autoreceptors.
Involvement of brain‐derived neurotrophic factor in cannabinoid receptor‐dependent protection against excitotoxicity
Authors: Khaspekov Leonid G. , Brenz Verca Maria S. , Frumkina Lidia E. , Hermann Heike , Marsicano Giovanni , Lutz Beat 
Published: April 2004

AbstractCannabinoid type 1 (CB1) receptors play a central role in the protection against excitotoxicity induced by treatment of mice with kainic acid (KA). As inactivation of CB1 receptor function in mice blocks KA‐induced increase of brain‐derived neurotrophic factor (BDNF) mRNA levels in hippocampus, the notion was put forward that BDNF might be a mediator, at least in part, of CB1 receptor‐dependent neuroprotection [Marsicano et al. (2003) Science, 302, 84–88]. To assess this signalling cascade in more detail, organotypic hippocampal slice cultures were used, as this in vitro system conserves morphological and functional properties of the hippocampus. Here, we show that both genetic ablation of CB1 receptors and pharmacological blockade with the specific CB1 receptor antagonist SR141716A increased the susceptibility of the in vitro cultures to KA‐induced excitotoxicity, leading to extensive neuronal death. Next, we found that the application of SR141716A to hippocampal cultures from wild‐type mice abolished the KA‐induced increase in BDNF protein levels. Therefore, we tried to rescue these organotypic cultures from neuronal death by exogenously applied BDNF. Indeed, BDNF was sufficient to prevent KA‐induced neuronal death after blockade of CB1 receptor signalling. In conclusion, our results strongly suggest that BDNF is a key mediator in CB1 receptor‐dependent protection against excitotoxicity, and further underline the physiological importance of the endogenous cannabinoid system in neuroprotection.
Mice lacking 5‐HT7 receptors show specific impairments in contextual learning
Authors: Roberts Amanda J. , Krucker Thomas , Levy Coree L. , Slanina Kristen A. , Sutcliffe J. Gregor , Hedlund Peter B. 
Published: April 2004

AbstractUsing 5‐HT7 receptor knockout mice it has been shown that the 5‐HT7 receptor is the main mediator of serotonin‐induced hypothermia but very little is known about the relevance of 5‐HT7 receptors in behaviour. We here report that lack of 5‐HT7 receptors leads to a specific learning deficit that is not due to general sensory or behavioural deficits. The knockout mice show impaired contextual fear conditioning but no significant deficits in motor and spatial learning or cued and operant conditioning. In addition, we demonstrate that 5‐HT7 receptor knockout mice display decreased long‐term synaptic plasticity within the CA1 region of the hippocampus. The results indicate an important role for the 5‐HT7 receptor in contextual hippocampal‐dependent learning and suggest a possible neuronal correlate for such a role is present within the CA1 region of the hippocampus.
Context‐dependent effects of CB1 cannabinoid gene disruption on anxiety‐like and social behaviour in mice
Authors: Haller J. , Varga B. , Ledent C. , Barna I. , Freund T. F. 
Published: April 2004

AbstractContrasting data were reported regarding the effects of cannabinoids on anxiety and social behaviour in both animals and humans. The cognitive effects of cannabinoids and their interactions with the HPA‐axis raise the possibility that cannabinoid effects are context but not behaviour specific. To assess this hypothesis, we submitted CB1 receptor knock‐out (CB1‐KO) and wild‐type (WT) mice to tests, which involved similar behaviours, but the behavioural context was different. The elevated plus‐maze test was performed under less and more anxiogenic conditions, i.e. under low and high light, respectively. We also compared the social behaviour of the two genotypes in the resident/intruder and social interaction tests. Both tests represent a social challenge and induce similar behaviours, but involve different contexts. The behaviour of CB1‐KO and WT mice was similar under low light, but CB1 gene disruption increased anxiety‐like behaviour under the high light condition. CB1 gene disruption promoted aggressive behaviour in the home‐cage, whereas it inhibited social behaviour in the unfamiliar cage. Thus, the anxiogenic‐like effect was restricted to the more stressful unfamiliar environment. These data suggest that the effects of CB1 gene disruption were context and not behaviour specific. Novelty stress resulted in higher ACTH levels in CB1‐KOs than in WTs, which suggests that context dependency occurred in conjunction with an altered HPA axis function. The present data at least partly explain contrasting effects of cannabinoids in different contexts as well as in different species and strains that show differential stress responses and coping strategies.
Neurons in hippocampal afferent zones of rat striatum parse routes into multi‐pace segments during maze navigation
Authors: Mulder Antonius B. , Tabuchi Eiichi , Wiener Sidney I. 
Published: April 2004

AbstractHippocampal ‘place’ neurons discharge when rats occupy specific regions within an environment. This finding is a cornerstone of the theory of the hippocampus as a cognitive map of space. But for navigation, representations of current position must be implemented by signals concerning where to go next, and how to get there. In recordings in hippocampal output structures associated with the motor system (nucleus accumbens and ventromedial caudate nucleus) in rats solving a plus‐maze, neurons fired continuously from the moment the rat left one location until it arrived at the next goal site, or at an intermediate place, such as the maze centre. While other studies have shown discharges during reward approach behaviours, this is the first demonstration of activity corresponding to the parsing of complex routes into sequences of movements between landmarks, similar to the lists of instructions we often employ to communicate directions to follow between points on a map. As these cells fired during a series of several paces or re‐orientation movements, perhaps this is homologous to ‘chunking’. The temporal overlaps in the activity profiles of the individual neurons provide a possible substrate to successively trigger movements required to arrive at the goal. These hippocampally informed, and in some cases, spatially selective responses support the view of the ventral striatum as an interface between limbic and motor systems, permitting contextual representations to have an impact on fundamental action sequences for goal‐directed behaviour.
On the regulation of NMDA receptors by nitric oxide
Authors: Hopper Rachel , Lancaster Barrie , Garthwaite John 
Published: April 2004

AbstractNitric oxide (NO) is generated in central synapses on activation of N‐methyl‐d‐aspartate (NMDA) receptors and exerts physiological effects by changing cGMP levels. NO has frequently also been claimed to engage a different mechanism, namely the covalent modification of thiol residues (S‐nitrosation), and thereby exert a negative feedback on NMDA receptors. Tests of this hypothesis were conducted by recording NMDA receptor‐mediated synaptic potentials in the CA1 area of rat hippocampal slices. Manipulations designed to increase or decrease endogenous NO levels had no effect. Addition of exogenous NO using a NONOate donor in concentrations up to 30‐fold higher than those needed to evoke maximal cGMP accumulation also had no effect. Nevertheless, in agreement with previous findings, photolysis of a caged NO derivative with UV light led to an enduring block of synaptic NMDA receptors. To address these contradictory results, NMDA receptor‐mediated currents were recorded from HEK‐293 cells transfected with NR1 and NR2A subunits. As found in slices, photolysis of caged NO inhibited the currents whereas perfusion of NO (up to 5 µm) was ineffective. However, when NO was supplied at a concentration found to be effective when released photolytically (5 µm) and the cells simultaneously exposed to the UV light used for photolysis, NMDA receptor‐mediated currents were inhibited. This effect was not observed at more physiological NO concentrations (10 nm range). The results indicate that neither endogenous NO nor exogenous NO in supra‐physiological concentration inhibits synaptic NMDA receptors; the combination of high NO concentration and UV light can give an artifactual result.
Differential distribution of calpain small subunit 1 and 2 in rat brain
Authors: Friedrich Peter , Papp Henrietta , Halasy Katalin , Farkas Attila , Farkas Bence , Tompa Peter , Kása Peter 
Published: April 2004

AbstractCalpains, the Ca2+‐dependent thiol proteases, are abundant in the nervous tissue. The ubiquitous enzyme forms in mammals are heterodimers consisting of a specific, µ or m, large (catalytic) subunit and, apparently, a common small (regulatory) subunit (CSS1). Recently, however, we described a second form of small subunit (CSS2), which is of restricted occurrence [Schád, E., Farkas, A., Jékely, G., Tompa, P. & Friedrich, P. (2002) Biochem. J., 362, 383–388]. Here we analysed the distribution of immunoreactivity in various parts of rat brain against two anti‐CSS1 and two anti‐CSS2 antibodies by correlated light and electron microscopy. Remarkably, the antibodies showed differential distribution in various parts of rat cortex: anti‐CSS1 reacted mainly with perikarya and dendrites, whereas anti‐CSS2 was more prominent in axons. In serial sections CSS2 and synaptophysin gave very similar patterns, i.e. these epitopes seem to colocalize. Electron microscopy confirmed that CSS1 was mainly localized postsynaptically in dendrites and somata, whereas CSS2 was found presynaptically. The hypothesis is advanced that these distinct distributions of calpain subunits may be related to the transport of these enzymes in nerve cells.