Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats.
We examined the potential protective effect of BDNF against beta-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 Abeta(1-42) and Abeta(25-35). It completely reversed the toxic action induced by Abeta(1-42) and partially that induced by Abeta(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, Abeta(25-35) was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Abeta(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 Abeta peptides.
Arancibia
S
S
Univ Montpellier 2, Montpellier, F-34095, France. sandor.arancibia@univ-montp2.fr
Silhol
M
M
Moulière
F
F
Meffre
J
J
Höllinger
I
I
Maurice
T
T
Tapia-Arancibia
L
L
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D020813:Receptor, trkB