Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor.
Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.
Rex
Christopher S
CS
Department of Neurobiology and Behavior, University of California at Irvine, 92697-4292, USA.
Lauterborn
Julie C
JC
Lin
Ching-Yi
CY
Kramár
Eniko A
EA
Rogers
Gary A
GA
Gall
Christine M
CM
Lynch
Gary
G
D000375:Aging / Q000523:psychology*; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D004569:Electroencephalography; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA