PMID- 20674095 OWN - NLM STAT- MEDLINE DCOM- 20120615 LR - 20220309 IS - 1558-1497 (Electronic) IS - 0197-4580 (Print) IS - 0197-4580 (Linking) VI - 33 IP - 4 DP - 2012 Apr TI - BDNF upregulation rescues synaptic plasticity in middle-aged ovariectomized rats. PG - 708-19 LID - 10.1016/j.neurobiolaging.2010.06.008 [doi] AB - Brain-derived neurotrophic factor (BDNF) has emerged as a possible broad-spectrum treatment for the plasticity losses found in rodent models of human conditions associated with memory and cognitive deficits. We have tested this strategy in the particular case of ovariectomy. The actin polymerization in spines normally found after patterned afferent stimulation was greatly reduced, along with the stabilization of long-term potentiation, in hippocampal slices prepared from middle-aged ovariectomized rats. Both effects were fully restored by a 60-minute infusion of 2 nM BDNF. Comparable rescue results were obtained after elevating endogenous BDNF protein levels in hippocampus with 4 daily injections of a short half-life ampakine (positive modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate [AMPA]-type glutamate receptors). These results provide the first evidence that minimally invasive, mechanism-based drug treatments can ameliorate defects in spine plasticity caused by depressed estrogen levels. CI - Copyright A(c) 2012 Elsevier Inc. All rights reserved. FAU - Kramar, Eniko A AU - Kramar EA AD - Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-4291, USA. ekramar@uci.edu FAU - Chen, Lulu Y AU - Chen LY FAU - Lauterborn, Julie C AU - Lauterborn JC FAU - Simmons, Danielle A AU - Simmons DA FAU - Gall, Christine M AU - Gall CM FAU - Lynch, Gary AU - Lynch G LA - eng GR - P01 NS045260-050003/NS/NINDS NIH HHS/United States GR - F31 MH083396/MH/NIMH NIH HHS/United States GR - R01 NS051823/NS/NINDS NIH HHS/United States GR - MH083396/MH/NIMH NIH HHS/United States GR - R01 NS051823-07/NS/NINDS NIH HHS/United States GR - NS051823/NS/NINDS NIH HHS/United States GR - NS045260/NS/NINDS NIH HHS/United States GR - P01 NS045260/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100731 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Estrogens) RN - 0 (Excitatory Amino Acid Agonists) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Electric Stimulation MH - Estradiol/pharmacology MH - Estrogens/pharmacology MH - Excitatory Amino Acid Agonists/pharmacology MH - Female MH - Hippocampus/*cytology/*drug effects MH - In Vitro Techniques MH - Long-Term Potentiation/drug effects/physiology MH - Ovariectomy MH - Rats MH - Rats, Long-Evans MH - Synapses/*drug effects MH - Up-Regulation/*drug effects PMC - PMC2978788 MID - NIHMS217868 COIS- Disclosure Statement. Drs. Kramar, Chen and Simmons have no potential conflicts of interest that could inappropriately influence this work. Drs. Lynch, Gall, and Lauterborn authored a patent (as inventors) assigned to The Regents of the University of California on the use of ampakines to up-regulate neurotrophic factor expression in brain (US patent 6,030,968). Dr. Lynch owns stock in Cortex Pharmaceuticals (<5% of outstanding shares), and is a consultant to the company. Dr. Lynch has received grants from Cortex Pharmaceuticals, including 1 year of support to initiate the present studies, but currently does not have such support. All sponsored research and consulting activities have been reviewed and approved by the Conflict of Interest Committee at University of California, Irvine. EDAT- 2010/08/03 06:00 MHDA- 2012/06/16 06:00 PMCR- 2013/04/01 CRDT- 2010/08/03 06:00 PHST- 2010/02/18 00:00 [received] PHST- 2010/04/30 00:00 [revised] PHST- 2010/06/12 00:00 [accepted] PHST- 2010/08/03 06:00 [entrez] PHST- 2010/08/03 06:00 [pubmed] PHST- 2012/06/16 06:00 [medline] PHST- 2013/04/01 00:00 [pmc-release] AID - S0197-4580(10)00273-3 [pii] AID - 10.1016/j.neurobiolaging.2010.06.008 [doi] PST - ppublish SO - Neurobiol Aging. 2012 Apr;33(4):708-19. doi: 10.1016/j.neurobiolaging.2010.06.008. Epub 2010 Jul 31.