Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats

Abstract

We examined the potential protective effect of BDNF against β-amyloid-induced neurotoxicity in vitro and in vivo in rats. In neuronal cultures, BDNF had specific and dose–response protective effects on neuronal toxicity induced by Aβ 1–42 and Aβ 25–35. It completely reversed the toxic action induced by Aβ 1–42 and partially that induced by Aβ 25–35. These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB.FL) were localized in vitro in cortical neurons (mRNA and protein). In in vivo experiments, Aβ 25–35 was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Aβ 25–35/BDNF interactions, i.e. local measurement of BDNF release, number of hippocampal hilar cells expressing SRIH mRNA and assessment of the corpus callosum damage (morphological examination, pyknotic nuclei counting and axon labeling with anti-MBP antibody). We conclude that BDNF possesses neuroprotective properties against toxic effects of Aβ peptides.