Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus.
Visual cortex ablation in newborn rats determines the almost complete degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of the geniculo-cortical fibres. Death of dLGN neurons is massive and rapid, and occurs by apoptosis. We recently showed that exogenous administration of the neurotrophin brain-derived neurotrophic factor (BDNF) in the eye prevents the degeneration of dLGN neurons occurring after visual cortex lesion in newborn rats. To elucidate the molecular mechanisms of BDNF-mediated neuroprotection, we sought to identify novel genes regulated by BDNF in the rat dLGN after visual cortex lesion. By using mRNA fingerprinting, we isolated a cDNA fragment upregulated in the dLGN of lesioned rats treated with BDNF. This cDNA fragment shared 100% homology with the rat cytosolic branched chain aminotransferase (BCATc), a key enzyme of glutamate metabolism. Quantitative reverse transcription-polymerase chain reaction and in situ hybridization confirmed that BCATc mRNA is markedly overexpressed by exogenous supply of BDNF to axotomized dLGNs. Immunohistochemical analysis showed that upregulation of BCATc in the dLGN of lesioned rats treated with BDNF takes place in astrocytes. These results suggest that modulation of glutamate metabolism by astrocytes might play an important role in BDNF-mediated survival of axotomized dLGN neurons.
Madeddu
Federico
F
Istituto di Neuroscienze del C.N.R., Pisa, Italy.
Naska
Sibel
S
Menna
Elisabetta
E
Chiellini
Chiara
C
Sweatt
Andrew J
AJ
Hutson
Susan M
SM
Benzi
Luca
L
Maffei
Margherita
M
Maffei
Lamberto
L
Bozzi
Yuri
Y
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002452:Cell Count; D016172:DNA Fingerprinting / Q000379:methods; D005829:Geniculate Bodies / Q000187:drug effects* / Q000201:enzymology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*; D014793:Visual Cortex / Q000187:drug effects / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D005968:Glutamate Decarboxylase; D010751:Phosphopyruvate Hydratase