title: Chronic estradiol treatment decreases brain derived neurotrophic factor (BDNF) expression and monoamine levels in the amygdala--implications for behavioral disorders.
abstract: Changes in serum estradiol levels are associated with mood disorders in women. However, the underlying mechanisms are not clear. Because alterations in Brain-Derived Neurotrophic Factor (BDNF) and monoamine levels in the hippocampus and amygdala have been associated with anxiety disorders, we hypothesized that chronic treatment with a low dose of estradiol would cause anxiety-like disorder by altering BDNF and monoamine levels in these regions. To test this hypothesis, female rats were sham-implanted (Controls) or implanted with pellets that release estradiol-17β (E2) for 90-days at the rate of 20 ng/day. Animals underwent behavioral tests such as the open field test and elevated plus maze test at the end of treatment. Brains from these animals were frozen, sectioned and the hippocampus, central amygdala and caudate putamen were microdissected and analyzed for monoamine levels using HPLC. BDNF protein levels in these areas were measured using ELISA and BDNF mRNA levels were analyzed using RT-PCR. In the open field test, animals chronically treated with E2 displayed anxiety-like behavior that was marked by a decrease in the number of inner zone crossings and increase in the rate of defecation compared to controls. However, no behavioral changes were observed in the elevated plus maze test. Chronic E2 treatment also decreased BDNF protein and mRNA levels in the central amygdala that was accompanied by a reduction in dopamine levels. No changes were observed in the hippocampus and caudate putamen. These results suggest that BDNF and dopamine in the central amygdala might possibly mediate chronic E2-induced behavioral alterations.
authors.affiliation: Neuroendocrine Research Laboratory, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Madhan
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Department of Neuroscience Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Nunez
authors.affiliation: Neuroendocrine Research Laboratory, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, United States.
authors.forename: Sheba M J
authors.initials: SM
authors.lastname: Mohankumar
authors.affiliation: Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, United States. Electronic address: mohankumar@cvm.msu.edu.
authors.forename: P S
authors.initials: PS
authors.lastname: Mohankumar
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004967:Estrogens; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D004958:Estradiol
keywords: Anxiety; BDNF; Behavior; Estradiol; Monoamines