Delayed NGF infusion fails to reverse axotomy-induced degeneration of basal forebrain cholinergic neurons in adult p75(LNTR)-deficient mice

Neuroscience
C E Van der Zee, T Hagg

Abstract

The p75 low-affinity neurotrophin receptor (p75(LNTR)) appears to have various functions that include enhancing nerve growth factor (NGF)-mediated survival by increasing TrkA (high-affinity NGF receptor) efficiency, and mediating apoptosis by acting as a ligand-regulated pro-apoptotic receptor. Here, we investigated the role of p75(LNTR) for adult cholinergic basal forebrain neurons by comparing neuronal responses to injury in control and p75(LNTR)-deficient mice. In both types of mice, approximately 70% of the cholinergic neurons in the ipsilateral medial septum had lost their markers choline acetyltransferase and tyrosine kinase A by 28 days following unilateral transection of the dorsal septohippocampal pathway (fimbria fornix). A 7-day delayed infusion of NGF that started 28 days after the injury resulted in reversal of choline acetyltransferase expression and cell atrophy in control, but not in p75(LNTR)-deficient, mice. This lack of response to delayed NGF treatment in p75(LNTR)-deficient mice was most likely not due to cell death, as all of the septohippocampal neurons, labeled with Fluorogold before the lesion, were present at 28 days post-lesion, similar to control mice. p75(LNTR)-deficient cholinergic neurons can resp...Continue Reading

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Citations

Jul 2, 2005·Experimental Brain Research·Klaus Oliver SchubertMatthias Kirsch
May 14, 2004·Journal of the Neurological Sciences·Kevin D Barron
Aug 15, 2006·The European Journal of Neuroscience·Stavroula SophouAthanasios Dinopoulos

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