p75NTR Expression is induced in isolated neurons of the penumbra after ischemia by cortical devascularization
2009
The p75 neurotrophin receptor (p75NTR) is involved in neuronal functions ranging from induction of apoptosis and growth inhibition to the promotion of survival. p75NTR expression is induced in the central nervous system (CNS) by a range of pathological conditions, where it seems to have a role in neuronal death and axonal growth inhibition. The cellular mechanisms driving p75NTR expression in cell lines and primary neurons is Sp1 dependent (Ramos et al. [2007] J. Neurosci. 27:1498). In this study, we analyzed the spatiotemporal profile of p75NTR expression after an ischemic lesion induced by cortical devascularization (CD). Our results show that p75NTR expression occurs in isolated neurons of the ischemic lesion site. The p75NTR+ neurons presented morphological alterations and active caspase-3 staining. Some p75NTR+ neurons were also positive for sortilin. The peak of p75NTR expression was localized 3 days postlesion (3DPL) in the penumbra. Sp1 transcription factor nuclear localization was observed in p75NTR+ neurons. The overall level of Sp1 expression was increased until 14DPL on the ipsilateral hemisphere. With primary cortical neurons, we demonstrated that p75NTR expression is induced by excitotoxic stress and correlated with increased Sp1 abundance. We conclude that p75NTR expression is localized in selected neurons of the ischemic lesion and that these neurons are probably condemned to apoptotic cell death. In primary neuronal culture, it is clear that excitotoxity and Sp1 are involved in induction of p75NTR expression, although, in vivo, some additional mechanisms are likely to be involved in the control of p75NTR expression in specific neurons in vivo. © 2009 Wiley-Liss, Inc.
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