The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice

Publication date: Available online 13 July 2016
Source:Neurobiology of Aging
Author(s): Alessia Bachis, Erin Wenzel, Allyssia Boelk, Jodi Becker, Italo Mocchetti
Human Immunodeficiency Virus-1 (HIV) and its envelope protein gp120 reduce synaptodendritic complexity. However, the mechanisms contributing to this pathological feature are still not understood. The proneurotrophin brain-derived neurotrophic factor (proBDNF) promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic (gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated neurotoxicity. Old (∼10 months) gp120tg mice, exhibited an increase in proBDNF levels in the hippocampus as well as a decrease in the number of dendritic spines when compared to age matched wild type. These effects were not observed in 3 or 6 month old mice. To test if the reduction in spine density and morphology is caused by the activation of p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of only one copy of the p75NTR gene in gp120tg mice is sufficient to normalize the number of hippocampal spines, strongly suggesting that the neurotoxic effect of gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could provide an adjunct therapy against synaptic simplification caused by HIV.



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