Neuroscience
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Comparative Study
The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain.
The cortical stab injury has been widely used for biochemical analysis of molecular changes following CNS injury. However, the cellular responses to this injury have not been accurately quantified. In order to provide a baseline for biochemical studies and future experiments on the manipulation of the CNS injury response we have undertaken a quantitative analysis of this injury. ⋯ They are likely to be blood-derived cells that express NG2 or have ingested it. NG2 immunohistochemistry and platelet-derived growth factor alpha receptor (PDGFalpha-R) in situ hybridisation on neighbouring sections was performed. In the lesioned area only 12% of NG2 positive (+ive) cells were PDGFalpha-R +ive (a ratio of 1:8 for PDGFalpha-R +ive cells: NG2 +ive cells) compared with 33% in the unlesioned cortex and an almost 100% overlap in the spinal cord.
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A growing body of evidence indicates that estrogens affect apoptotic processes in neuronal cells. However, their effects seem to depend on type of neuronal tissue, stage of development and apoptosis inducing factors. In the present study we compared effects of estrone (100 and 500 nM) on N-methyl-D-aspartic acid (NMDA) (1 mM)- and staurosporine (1 microM)-induced caspase-3-like activity and lactate dehydrogenase (LDH)-release in primary cultures of rat hippocampal and neocortical neurons. ⋯ In contrast to NMDA, staurosporine elevated caspase-3-like activity and LDH-release in a time-dependent manner in all used culture systems. Estrone inhibited pro-apoptotic effects of staurosporine in neocortical neurons, but only at later stage of development in vitro, which points to the protective role of estrogens during the brain tissue maturation. Since estrone triggered its effects via non-genomic mechanisms, it suggests that the other estradiol metabolites exhibiting low affinity to hormone receptors may be potent neuroprotective agents, which could retain the favorable and minimize the adverse side effects of estrogens.
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Comparative Study
Region specific changes in forebrain 5-hydroxytryptamine1A and 5-hydroxytryptamine2A receptors in isolation-reared rats: an in vitro autoradiography study.
The neurochemical correlates of the behavioural consequences of isolation rearing of rats are complex and involve many neurotransmitters, including the serotonergic system. Impaired functioning of the ascending serotonergic system has been implicated in many neuropsychiatric syndromes, including attention deficit hyperactivity disorder and schizophrenia. In the present investigation serotonergic function was assessed using in vitro receptor autoradiography. ⋯ By contrast, 5-HT(1A) receptor binding site densities were significantly reduced by 22% in the prelimbic cortex, and significantly increased by between 10 and 50% in the motor cortex, somatosensory cortex, dentate gyrus and CA fields of the hippocampus. These data demonstrate that isolation-rearing produces significant effects on forebrain 5-HT(1A) and 5-HT(2A) receptor densities in the adult rat. It is hypothesised that altered serotonergic function, particularly in the hippocampus and prefrontal cortex, may underlie some of the behavioural abnormalities associated with isolation-rearing.
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Comparative Study
Development and aging of N-methyl-D-aspartate receptor expression in the prefrontal/frontal cortex of mice.
The present study was designed to determine whether the changes that occur during aging in the expression of the N-methyl-D-aspartate (NMDA) receptor and two NMDA receptor subunits, zeta1 and epsilon2, are a continuation of developmental processes and whether protein and mRNA expression patterns of the subunits are similar across the lifespan. The prefrontal/frontal cortex of C57BL/6 mice of eight different ages (7-8, 13-15, 30-32, 49-53, and 70-72 days and 4.5, 11, and 25 months of age) were used to examine NMDA-displaceable [(3)H]glutamate binding and mRNA in tissue sections and mRNA and protein from homogenates. The lateral prefrontal/frontal cortex of C57BL/6 mice showed more significant declines in density of agonist binding to NMDA receptors during both development and aging than the medial cortex. ⋯ The developmental expression of the zeta1subunit in the prefrontal/frontal cortex was influenced by gender and there was no significant effect of adult aging on either the protein or mRNA expression of this subunit. Determining how the expression of the NMDA receptor and its subunits change throughout the lifespan can help us to better understand the processes affecting the receptor during aging. These results should be useful for designing interventions into the aging process to repair or prevent changes in the NMDA receptor and its associated functions, such as learning and memory.
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In Parkinson's disease the neurones of the subthalamic nucleus show increased synchrony and oscillatory burst discharge, thought to reflect a breakdown of parallel processing in basal ganglia circuitry. To understand better the mechanisms underlying this transition, we sought to mimic this change in firing pattern within sagittal slices of rat midbrain. The firing patterns of up to four simultaneously extracellularly recorded subthalamic nucleus (STN) neurones were analysed using burst and oscillation detection programs, and correlated activity between pairs of neurones assessed. ⋯ As the bursting seen here was unaccompanied by the synchronous activity that has often been observed (pathologically) in vivo, it probably reflects solely intrinsic STN neuronal properties, rather than network activity. No functional role was found for glutamatergic collaterals within the STN, either when cells are firing tonically or burst firing. The circuitry needed to produce synchrony in the STN is most likely not intrinsic to the STN itself, but requires connections with other basal ganglia nuclei, and/or the cortex, which are not present in this preparation.