Brain Derived Neutrophic Factor (BDNF)
“Alterations in Brain-derived Neurotrophic Factor in an Animal Modell of Schizophrenia
The significant amount of research supporting a role for neurodevelopmental abnormalities resulting in a predisposition to schizophrenia and consequent neurodegenerative processes led to an investigation of alterations in brain-derived neurotrophic factor (BDNF) in an animal model of schizophrenia.
In the hippocampus, cortex and in vitro, BDNF has been demonstrate to regulate the survival, differentiation, morphology and synaptic remodeling of neurons.
(Alderson et al., 1990, Ghosh eta/., 1994, ]ones, K.R. eta/., 1994, Korte eta/., 1995, McCallister eta/., 1995, Thoenen, 1995).
It has also been demonstrated to modulate neurotransmitter synthesis, metabolism and release, postsynaptic ion channel fluxes, neuronal activity and long term potentiation.
(Altar eta/., 1997, Croll et a/., 1994, Kang and Schuman, 1995, Thoenen, 1995).
Reports demonstrate a reduction in hippocampal BDNF mRNA (Brouha eta/., 1996) and serum BDNF in schizophrenic patients (Toyooka eta/., 1999). An allele variant of the BDNF gene has also been identified in a population of schizophrenic patients (Vicente eta/., 1996).
In addition, support for a role for BDNF in schizophrenia also stems from the demonstration that it is decreased by factors correlated with first episode onset such as stress (Smith et a/., 1995a, 1995b) and estrogen withdrawal.
(Singh eta/., 1995). Interestingly, these stress induced decreases in BDNF are blocked by 5-HT2 receptor antagonists, a receptor binding property of many neuroleptics (Vaidya eta/., 1997).
Electroconvulsive treatment (ECT), effective in treatment-resistant schizophrenia in combination with neuroleptics (Sajatovic and Meltzer, 1993), also upregulates the expression of BDNF
(Lindefors eta/., 1995, Nibuya eta/., 1995).
For these reasons, in addition to providing a link between neurodevelopmental and neurodegenerative phenomenon, BDNF is an attractive candidate molecule in schizophrenia. “
