BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs.
Brain-derived neurotrophic factor (BDNF) plays an important role in development, synapse remodelling and responses to stress and injury. Its abnormal expression has been implicated in schizophrenia, a neuropsychiatric disorder in which abnormal neural development of the hippocampus and prefrontal cortex has been postulated. To clarify the effects of antipsychotic drugs used in the therapy of schizophrenia on BDNF mRNA, we studied its expression in rats treated with clozapine and haloperidol and in rats with neonatal lesions of the ventral hippocampus, used as an animal model of schizophrenia. Both antipsychotic drugs reduced BDNF expression in the hippocampus of control rats, but did not significantly lower its expression in the prefrontal cortex. The neonatal hippocampal lesion itself suppressed BDNF mRNA expression in the dentate gyrus and tended to reduce its expression in the prefrontal cortex. These results indicate that, unlike antidepressants, antipsychotics down-regulate BDNF mRNA, and suggest that their therapeutic properties are not mediated by stimulation of this neurotrophin. To the extent that the lesioned rat models some pathophysiological aspects of schizophrenia, our data suggest that a neurodevelopmental insult might suppress expression of the neurotrophin in certain brain regions.
Lipska
B K
BK
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, 20892-1385 USA. lipskab@intra.nimh.gov
Khaing
Z Z
ZZ
Weickert
C S
CS
Weinberger
D R
DR
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003024:Clozapine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000601:surgery; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D003024:Clozapine; D006220:Haloperidol