The Fragile-X mental retardation protein, the protein absent in Fragile-X syndrome, is synthesized near synapses upon neurotransmitter activation. Humans and mice lacking this protein exhibit abnormal dendritic spine ...
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The Fragile-X mental retardation protein, the protein absent in Fragile-X syndrome, is synthesized near synapses upon neurotransmitter activation. Humans and mice lacking this protein exhibit abnormal dendritic spine lengths and numbers. Here we investigated Fragile-X protein levels in animals exposed to behavioral paradigms that induce neuronal morphological change. Fragile-X protein immunoreactivity was examined in visual cortices of rats reared in a complex environment for 10 or 20 days, motor cortices of rats trained on motor-skill tasks for 3 or 7 days, and either visual or motor cortices of inactive controls. Rats exposed to a complex environment for 20 days or trained for 7 days on motor-skill tasks exhibited increased Fragile-X protein immunoreactivity in visual or motor cortices, respectively. These results provide the first evidence for a behaviorally induced alteration of Fragile-X protein expression and are compatible with previous findings suggesting synaptic regulation of its expression. These results also strengthen the association of Fragile-X mental retardation protein expression with the alteration of synaptic structure. (C) 2000 Academic Press.
Cognitive impairment is an early symptom of Huntington's disease (HD), Mice engineered to carry the HD mutation in the endogenous huntingtin gene showed a significant reduction in long-term potentiation (LTP), a m...
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Cognitive impairment is an early symptom of Huntington's disease (HD), Mice engineered to carry the HD mutation in the endogenous huntingtin gene showed a significant reduction in long-term potentiation (LTP), a measure of synaptic plasticity often thought to be involved in memory, However, LTP could be induced in mutant slices by an 'enhanced' tetanic stimulus, implying that the LTP-producing mechanism is intact in mutant mice, but that their synapses are less able to reach the threshold for LTP induction, Mutant mice showed less post-tetanic potentiation than wild-type animals, and also st-sowed decreased paired pulse facilitation, suggesting that excitatory synapses in HD mutant mice are impaired in their ability to sustain transmission during repetitive stimulation. We show that mutants, while normal in their ability to transmit at low frequencies, released significantly less glutamate during higher frequency synaptic activation. Thus, a reduced ability of Huntington synapses to respond to repetitive synaptic demand of even moderate frequency could result not only in a functional impairment of LTP induction, but could also serve as a substrate for the cognitive symptoms that comprise the early-stage pathology of HD.
The adult hypothalamo-neurohypophysial system undergoes activity-dependent, reversible morphological changes which result in reduced astrocytic coverage of its neurones and an increase in their synaptic contacts. Our ...
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The adult hypothalamo-neurohypophysial system undergoes activity-dependent, reversible morphological changes which result in reduced astrocytic coverage of its neurones and an increase in their synaptic contacts. Our recent observations show that neurones and glia of the hypothalamo-neurohypophysial system continue to express 'embryonic' molecular features which may underlie their capacity to undergo such plasticity. These include expression of cell surface molecules Like the glycosyl phosphatidyl inositol (GPI)-linked glycoprotein F3, which intervenes in axonal outgrowth, and the polysialylated isoform of the neural cell adhesion molecule (PSA-NCAM), which reduces cell adhesion and promotes dynamic cell interactions. F3 is colocalised with vasopressin and oxytocin hormones in neurosecretory granules and follows an activity-dependent, regulated pathway for surface expression on neurohypophysial axons. In contrast, PSA-NCAM appears to follow a constitutive pathway, independent of the activity of the hypothalamo-neurohypophysial system, for expression on axonal and glial surfaces, in the hypothalamic magnocellular nuclei and in the neurohypophysis. The role of F3 remains to be determined but in view of its presumptive functions during development, we propose that it promotes remodelling of neurosecretory terminals. On the other hand, we provide direct evidence that surface expression of PSA on NCAM is essential to morphological plasticity since its specific enzymatic degradation in vivo inhibited the neuronal-glial and synaptic changes normally induced by stimulation of secretion from the hypothalamo-neurohypophysial system.
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