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Status epilepticus induces a TrkB to p75 neurotrophin receptor switch and increases brain-derived neurotrophic factor interaction with p75 neurotrophin receptor: an initial event in neuronal injury induction.

Abstract：

:In neuronal cultures it has been demonstrated that neurotrophins can elicit neuronal death through the p75 neurotrophic receptor (p75ntr) in the absence of concomitant Trk signaling. However, it was suggested that p75ntr induces neuronal death after status epilepticus (SE) in neuronal populations that express relatively high quantities of tropomyosin receptor kinase B (TrkB). Here, using Western blot and immunohistochemistry analyses in the hippocampus, we found that 3-h SE caused a remarkable decrease in TrkB expression and phosphorylation, and a significant increase in p75ntr. TrkB modification occurs before the overexpression of the tumor suppressor protein p53, accompanies the cell damage taking place in the dentate gyrus, and precedes the CA1 neuronal injury as assessed by Fluoro-Jade B and Nissl staining. Co-immunoprecipitation of brain-derived neurotrophic factor (BDNF) or its immature form proBDNF showed increased interaction with p75ntr after its binding to TrkB was reduced. Interestingly, proBDNF also increases its binding with p75ntr after seizures that do not cause neuronal death (animals injected with pilocarpine that fail to enter SE). However, in those animals, TrkB protein levels remained unchanged and its phosphorylation increased. Our results indicate an intrinsic capacity of neurons in vivo to modify final neurotrophin output by changing the proportion of their receptors' expression and the receptors' interaction with their ligands. These early events support the idea that neurotrophins may be involved in the induction of neuronal death in vivo under pathological conditions.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Unsain N,Nuñez N,Anastasía A,Mascó DH

doi

10.1016/j.neuroscience.2008.04.038

subject

Has Abstract

pub_date

2008-06-26 00:00:00

pages

978-93

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(08)00567-8

journal_volume

154

pub_type

杂志文章

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Status epilepticus induces a TrkB to p75 neurotrophin receptor switch and increases brain-derived neurotrophic factor interaction with p75 neurotrophin receptor: an initial event in neuronal injury induction.