QBI Neuroscience Seminar: 'The p75 neurotrophin receptor is a necessary mediator of synaptic and behavioral changes induced by sleep deprivation'
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- A/Professor Sajikumar Sreedharan - Department of Physiology,
Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597
Title: 'The p75 neurotrophin receptor is a necessary mediator of synaptic and behavioral changes induced by sleep deprivation'
Abstract: Sleep deprivation (SD) interferes with cognitive functions, specifically hippocampal synaptic plasticity, including the long-lasting form of synaptic plasticity such as late long-term potentiation (late-LTP) and memory consolidation. However, the molecular mechanisms underlying these effects are not completely understood. I will present data on how SD impairs the cellular associative mechanism such as synaptic tagging and capture (STC), a major mechanism of associative learning and memory. The mutant mice lacking the p75 neurotrophin receptor (p75NTR) are resistant to the effects of SD on late-LTP and STC, both at cellular and behavioral levels. Mechanistically, deletion of p75NTR prevents the upregulation of phosphodiesterase PDE4A5 and decrease in BDNF, ERK1/2 and CREB activation that normally accompany SD. Our results identify p75NTR as an important mediator of the synaptic changes associated with SD, and suggest that targeting p75NTR could be a promising strategy to limit the cognitive deficits that accompany sleep loss.
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