PMID- 23276673 OWN - NLM STAT- MEDLINE DCOM- 20131017 LR - 20211021 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 239 DP - 2013 Jun 3 TI - Brain-derived neurotrophic factor-estrogen interactions in the hippocampal mossy fiber pathway: implications for normal brain function and disease. PG - 46-66 LID - S0306-4522(12)01217-1 [pii] LID - 10.1016/j.neuroscience.2012.12.029 [doi] AB - The neurotrophin brain-derived neurotrophic factor (BDNF) and the steroid hormone estrogen exhibit potent effects on hippocampal neurons during development and in adulthood. BDNF and estrogen have also been implicated in the etiology of diverse types of neurological disorders or psychiatric illnesses, or have been discussed as potentially important in treatment. Although both are typically studied independently, it has been suggested that BDNF mediates several of the effects of estrogen in the hippocampus, and that these interactions play a role in the normal brain as well as disease. Here we focus on the mossy fiber (MF) pathway of the hippocampus, a critical pathway in normal hippocampal function, and a prime example of a location where numerous studies support an interaction between BDNF and estrogen in the rodent brain. We first review the temporal and spatially regulated expression of BDNF and estrogen in the MFs, as well as their receptors. Then we consider the results of studies that suggest that 17beta-estradiol alters hippocampal function by its influence on BDNF expression in the MF pathway. We also address the hypothesis that estrogen influences the hippocampus by mechanisms related not only to the mature form of BDNF, acting at trkB receptors, but also by regulating the precursor, proBDNF, acting at p75NTR. We suggest that the interactions between BDNF and 17beta-estradiol in the MFs are potentially important in the normal function of the hippocampus, and have implications for sex differences in functions that depend on the MFs and in diseases where MF plasticity has been suggested to play an important role, Alzheimer's disease, epilepsy and addiction. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Harte-Hargrove, L C AU - Harte-Hargrove LC AD - Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, USA. FAU - Maclusky, N J AU - Maclusky NJ FAU - Scharfman, H E AU - Scharfman HE LA - eng GR - T32 MH067763/MH/NIMH NIH HHS/United States GR - MH-097763/MH/NIMH NIH HHS/United States GR - R01 NS037562/NS/NINDS NIH HHS/United States GR - R01 DA008259/DA/NIDA NIH HHS/United States GR - MH-067763/MH/NIMH NIH HHS/United States GR - NS-37562/NS/NINDS NIH HHS/United States GR - DA-008259/DA/NIDA NIH HHS/United States GR - R21 MH084215/MH/NIMH NIH HHS/United States GR - R56 NS037562/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20121229 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Estrogens) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Estrogens/*metabolism MH - Humans MH - Mossy Fibers, Hippocampal/*metabolism MH - Signal Transduction/*physiology PMC - PMC3628287 MID - NIHMS432291 EDAT- 2013/01/02 06:00 MHDA- 2013/10/18 06:00 PMCR- 2014/06/03 CRDT- 2013/01/02 06:00 PHST- 2012/11/29 00:00 [received] PHST- 2012/12/13 00:00 [accepted] PHST- 2013/01/02 06:00 [entrez] PHST- 2013/01/02 06:00 [pubmed] PHST- 2013/10/18 06:00 [medline] PHST- 2014/06/03 00:00 [pmc-release] AID - S0306-4522(12)01217-1 [pii] AID - 10.1016/j.neuroscience.2012.12.029 [doi] PST - ppublish SO - Neuroscience. 2013 Jun 3;239:46-66. doi: 10.1016/j.neuroscience.2012.12.029. Epub 2012 Dec 29.