PMID- 11860494 OWN - NLM STAT- MEDLINE DCOM- 20020412 LR - 20190815 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 14 IP - 12 DP - 2001 Dec TI - Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. PG - 1992-2002 AB - We investigated the possibility that estrogen and exercise interact in the hippocampus and regulate brain-derived neurotrophic factor (BDNF), a molecule increasingly recognized for its role in plasticity and neuron function. An important aspect of this study is to examine the effect of different time intervals between estrogen loss and estrogen replacement intervention. We demonstrate that in the intact female rat, physical activity increases hippocampal BDNF mRNA and protein levels. However, the exercise effect on BDNF up-regulation is reduced in the absence of estrogen, in a time-dependent manner. In addition, voluntary activity itself is stimulated by the presence of estrogen. In exercising animals, estrogen deprivation reduced voluntary activity levels, while estrogen replacement restored activity to normal levels. In sedentary animals, estrogen deprivation (ovariectomy) decreased baseline BDNF mRNA and protein, which were restored by estrogen replacement. Despite reduced activity levels in the ovariectomized condition, exercise increased BDNF mRNA levels in the hippocampus after short-term (3 weeks) estrogen deprivation. However, long-term estrogen-deprivation blunted the exercise effect. After 7 weeks of estrogen deprivation, exercise alone no longer affected either BDNF mRNA or protein levels. However, exercise in combination with long-term estrogen replacement increased BDNF protein above the effects of estrogen replacement alone. Interestingly, protein levels across all conditions correlated most closely with mRNA levels in the dentate gyrus, suggesting that expression of mRNA in this hippocampal region may be the major contributor to the hippocampal BDNF protein pool. The interaction of estrogen, physical activity and hippocampal BDNF is likely to be an important issue for maintenance of brain health, plasticity and general well-being, particularly in women. FAU - Berchtold, N C AU - Berchtold NC AD - Institute for Brain Aging and Dementia, 1226 Gillespie Neuroscience Facility, University of California, Irvine, CA 92697-4540, USA. nberchto@uci.edu FAU - Kesslak, J P AU - Kesslak JP FAU - Pike, C J AU - Pike CJ FAU - Adlard, P A AU - Adlard PA FAU - Cotman, C W AU - Cotman CW LA - eng GR - AG 13880/AG/NIA NIH HHS/United States GR - AG 15961/AG/NIA NIH HHS/United States GR - R01 AG 13411-04/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Estrogens) RN - 0 (RNA, Messenger) SB - IM MH - Aging/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Estrogen Replacement Therapy MH - Estrogens/blood/*deficiency/pharmacology MH - Female MH - Gene Expression Regulation/drug effects/*physiology MH - Hippocampus/drug effects/*metabolism MH - Menopause/*metabolism MH - Motor Activity/drug effects/physiology MH - Neurons/drug effects/metabolism MH - Physical Conditioning, Animal/*physiology MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors MH - Up-Regulation/drug effects/physiology EDAT- 2002/02/28 10:00 MHDA- 2002/04/16 10:01 CRDT- 2002/02/28 10:00 PHST- 2002/02/28 10:00 [pubmed] PHST- 2002/04/16 10:01 [medline] PHST- 2002/02/28 10:00 [entrez] AID - 1825 [pii] AID - 10.1046/j.0953-816x.2001.01825.x [doi] PST - ppublish SO - Eur J Neurosci. 2001 Dec;14(12):1992-2002. doi: 10.1046/j.0953-816x.2001.01825.x.