PMID- 24361909 OWN - NLM STAT- MEDLINE DCOM- 20141006 LR - 20140203 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 261 DP - 2014 Mar 15 TI - Chronic estradiol treatment decreases brain derived neurotrophic factor (BDNF) expression and monoamine levels in the amygdala--implications for behavioral disorders. PG - 127-33 LID - S0166-4328(13)00761-4 [pii] LID - 10.1016/j.bbr.2013.12.018 [doi] AB - 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-17beta (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. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Balasubramanian, Priya AU - Balasubramanian P AD - Neuroendocrine Research Laboratory, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, United States. FAU - Subramanian, Madhan AU - Subramanian M AD - Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, United States. FAU - Nunez, Joseph L AU - Nunez JL AD - Department of Neuroscience Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, United States. FAU - Mohankumar, Sheba M J AU - Mohankumar SM AD - Neuroendocrine Research Laboratory, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, United States. FAU - Mohankumar, P S AU - Mohankumar PS AD - Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, United States. Electronic address: mohankumar@cvm.msu.edu. LA - eng GR - AG027697/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131219 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Estrogens) RN - 0 (Neurotransmitter Agents) RN - 0 (RNA, Messenger) RN - 4TI98Z838E (Estradiol) SB - IM MH - Amygdala/*drug effects/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Chromatography, High Pressure Liquid MH - Chromatography, Liquid MH - Estradiol/*pharmacology MH - Estrogens/*pharmacology MH - Exploratory Behavior/drug effects MH - Female MH - Gene Expression Regulation/*drug effects MH - Maze Learning/drug effects MH - Neurotransmitter Agents/metabolism MH - RNA, Messenger MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Anxiety OT - BDNF OT - Behavior OT - Estradiol OT - Monoamines EDAT- 2013/12/24 06:00 MHDA- 2014/10/07 06:00 CRDT- 2013/12/24 06:00 PHST- 2013/07/21 00:00 [received] PHST- 2013/12/03 00:00 [revised] PHST- 2013/12/09 00:00 [accepted] PHST- 2013/12/24 06:00 [entrez] PHST- 2013/12/24 06:00 [pubmed] PHST- 2014/10/07 06:00 [medline] AID - S0166-4328(13)00761-4 [pii] AID - 10.1016/j.bbr.2013.12.018 [doi] PST - ppublish SO - Behav Brain Res. 2014 Mar 15;261:127-33. doi: 10.1016/j.bbr.2013.12.018. Epub 2013 Dec 19.