Influence of estradiol, stress, and 5-HT2A agonist treatment on brain-derived neurotrophic factor expression in female rats.
BACKGROUND
Estradiol affects neuronal plasticity, mood, and cognition. We examined the effects of the estrous cycle, acute and chronic estradiol treatments on BDNF mRNA expression in the hippocampus and cortex of female rats. The roles of 5-HT2A receptors and of stress on the BDNF mRNA regulation were also explored.


METHODS
BDNF mRNA levels were measured using in situ hybridization at proestrus and estrus, and following acute and chronic estradiol treatment of acutely and chronically ovariectomized (OVX) female rats. Some rats were pretreated with 5-HT2A agonist and antagonist, and another group was subjected to two-hour immobilization stress.


RESULTS
BDNF mRNA levels in the dentate gyrus and the medial prefrontal cortex were decreased during estrus, when estradiol levels are highest. Acute estradiol treatment decreased hippocampal BDNF mRNA in acutely OVX rats, but neither acute nor chronic estradiol had effect in chronically OVX rats. Estradiol pretreatment reduced the 5-HT2A receptor-mediated cortical upregulation in BDNF mRNA and did not effect the stress-induced down-regulation of BDNF mRNA in the dentate gyrus.


CONCLUSIONS
The duration of the estradiol treatment and the duration of the ovarian hormone deprivation are important factors in the regulation of BDNF synthesis and possibly in the functional outcome of estrogen treatment.
Cavus
Idil
I
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Duman
Ronald S
RS
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007103:Immobilization; D017403:In Situ Hybridization; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D004958:Estradiol