BDNF upregulation rescues synaptic plasticity in middle-aged ovariectomized rats.
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 α-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.
Kramár
Enikö A
EA
Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-4291, USA. ekramar@uci.edu
Chen
Lulu Y
LY
Lauterborn
Julie C
JC
Simmons
Danielle A
DA
Gall
Christine M
CM
Lynch
Gary
G
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004558:Electric Stimulation; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D004967:Estrogens; D018690:Excitatory Amino Acid Agonists; D004958:Estradiol