Hippocampus
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Voluntary wheel-running induces a rapid increase in proliferation and neurogenesis by neural precursors present in the adult rodent hippocampus. In contrast, the responses of hippocampal and other central nervous system neural precursors following longer periods of voluntary physical activity are unclear and are an issue of potential relevance to physical rehabilitation programs. We investigated the effects of a prolonged, 6-week voluntary wheel-running paradigm on neural precursors of the CD1 mouse hippocampus and forebrain. ⋯ The effects of prolonged wheel-running were also detected beyond the hippocampus. Unlike short-term wheel-running, prolonged wheel-running was associated with higher numbers of proliferating cells within the ventral forebrain subventricular region, a site of age-associated decreases in neural precursor proliferation and neurogenesis. Collectively, these findings indicate that (i) prolonged voluntary wheel-running maintains an increased level of hippocampal neurogenesis whose magnitude is linked to total running performance, and (ii) that it influences multiple neural precursor populations of the adult mouse brain.
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It has been well-established that cell proliferation and neurogenesis in the adult mouse dentate gyrus (DG) can be regulated by voluntary exercise. Recent evidence has suggested that the effects of voluntary exercise can in turn be influenced by environmental factors that regulate the amount of stress an animal is exposed to. In this study, we use bromodeoxyuridine and proliferating cell nuclear antigen immunohistochemistry to show that voluntary exercise produces a significant increase in cell proliferation in the adult mouse DG in both isolated and socially housed mice. ⋯ Although social condition did not regulate proliferation in young adult mice, an effect of social housing could be observed in mice exposed to acute restraint stress. Surprisingly, only exercising mice housed in isolated conditions showed an increase in cellular proliferation following restraint stress, whereas socially housed, exercising mice, failed to show a significant increase in proliferation. These findings indicate that social housing may increase the effects of any stressful episodes on hippocampal neurogenesis in the mouse DG.
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The potential of exercise or environmental enrichment to prevent or reverse age-related cognitive decline in rats has been widely investigated. The data suggest that the efficacy of these interventions as neuroprotectants may depend upon the duration and nature of the protocols and age of onset. Investigations of the mechanisms underlying these neuroprotective strategies indicate a potential role for the neurotrophin family of proteins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). ⋯ Significant correlations were observed between both learning and LTP and the expression of NGF and BDNF mRNA in the dentate gyrus. We conclude that decreased expression of NGF and BDNF in the dentate gyrus of aged rats is associated with impaired LTP and spatial learning. We suggest that the reversal of these age-related impairments by enrichment and exercise may be linked with prevention of the age-related decline in expression of these growth factors and, furthermore, that enrichment is as efficacious as exercise in preventing this age-related decline.
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Galantamine, a novel Alzheimer's drug, is known to inhibit acetylcholinesterase activity and potentiate nicotinic acetylcholine receptor (nAChR) in the brain. We previously reported that galantamine potentiates the NMDA-induced currents in primary cultured rat cortical neurons. We now studied the effects of galantamine on long-term potentiation (LTP) in the rat hippocampal CA1 regions. ⋯ Furthermore, LTP potentiation induced by galantamine treatment at 1 microM was closely associated with both CaMKII and PKC activation with concomitant increase in phosphorylation of their downstream substrates except for synapsin I. In addition, the enhancement of LTP by galantamine was accompanied with alpha7-type nAChR activation. These results suggest that galantamine potentiates NMDA receptor-dependent LTP through alpha7-type nAChR activation, by which the postsynaptic CaMKII and PKC are activated.
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It has been argued that a neural system including the hippocampus, fornix, mamillary bodies, and anterior thalamus is specifically involved in recollection, but not in familiarity based memory processes. Here we test this hypothesis using a task of episodic-like memory within an E-shaped maze. Animals seek out a preferred object (what) in a particular location (where) that is unique to a particular context (which occasion). ⋯ Animals with fornix lesions are impaired at recalling a past event. However, the same animals on the same trials show no such impairment in a judgement of familiarity. We therefore demonstrate that recall is dependent upon the fornix, while familiarity based memory is not.