BDNF down-regulates the caspase 3 pathway in injured geniculo-cortical neurones.
Visual cortex ablation in newborn rats causes a rapid and almost complete degeneration of neurones in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of geniculo-cortical fibres. Death of dLGN neurones occurs by apoptosis and is partially prevented (approximately 50%) by intraocular delivery of brain-derived neurotrophic factor (BDNF). Here we investigated the molecular mechanisms of BDNF-mediated neuroprotection. We found that exogenous administration of BDNF partially decreases (approximately 50%) the up-regulation of apoptotic proteins (phosphorylated c-Jun, cytochrome C and cleaved caspase 3), that occurs in dLGN neurones following visual cortex ablation at postnatal day 7. These results demonstrate that the neuroprotective action of BDNF on axotomised dLGN neurones involves the partial blockade of well-characterised apoptotic pathways.
Istituto di Neuroscienze del CNR, via Moruzzi 1, 56100 Pisa, Italy.
Federico
F
Madeddu
Sibel
S
Naska
Yuri
Y
Bozzi
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D045304:Cytochromes c / Q000378:metabolism; D003655:Decerebrate State / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005829:Geniculate Bodies / Q000166:cytology* / Q000293:injuries; D007150:Immunohistochemistry / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D014793:Visual Cortex / Q000293:injuries / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009687:Nuclear Proteins; D016759:Oncogene Protein p65(gag-jun); D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases