Post-stress changes in BDNF and Bcl-2 immunoreactivities in hippocampal neurons: effect of chronic administration of olanzapine.
In the present study, we used a repeated restraint stress animal model to observe the changes in the expression of brain-derived neurotrophic factor (BDNF) and B cell lymphoma protein-2 (Bcl-2) in hippocampal neurons of rats, monitored the time course of the expression over 3 weeks post-stress period, and examined the effects of the chronic administration of olanzapine on the time course. Olanzapine is an atypical antipsychotic drug that has been shown to be neuroprotective in previous in vitro studies. We found: (1) the repeated restraint stress decreases the levels of expression of BDNF and Bcl-2 in hippocampal neurons; (2) the stress-induced decreases spontaneously recover to their pre-stress levels in 3 weeks after the last stress exposure; (3) administration of olanzapine for 1 week returns the expression of Bcl-2 to its pre-stress level, and the administration for 3 weeks causes an excessive expression of BDNF in hippocampal neurons. In the context of the lower levels of BDNF and Bcl-2, and structural brain abnormalities observed in patients with schizophrenia, our findings suggest that BDNF and Bcl-2 may be involved in the pathophysiology of schizophrenia and in the therapeutic action of atypical antipsychotic drugs.
Neuropsychiatric Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, SK, Canada S7N 5E4.
Can
C
Luo
Haiyun
H
Xu
Xin-Min
XM
Li
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000096:biosynthesis*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D001569:Benzodiazepines; D000077152:Olanzapine