One more - Short acting Ampakine given BID for 4 days boosts BDNF and restores LTP in rats. This gives support to Dr. Lynch's "burst" dosing strategy using ultra short acting high impacts -
>>> Program#/Poster#: 423.22/C14
Title: In vivo administration of ampakine to middle-aged rats elevates BDNF and rescues LTP stabilization
Location: Georgia World Congress Center: Halls B3-B5
Presentation Start/End Time: Monday, Oct 16, 2006, 2:00 PM - 3:00 PM
Authors: *C. S. REX1, J. C. LAUTERBORN2, E. A. KRAMAR3, G. A. ROGERS4, C. M. GALL5, G. LYNCH6;
1Dept Neurobiology & Behavior, Univ California Irvin, Irvine, CA, 2Dept Anatomy & Neurobiology, Univ California Irvin, Irvine, CA, 3Dept Psychiatry & Human Behavior, Univ California Irvin, Irvine, CA, 4'', Cortex Pharmaceuticals, Inc, Irvine, CA, 5Dept Anatomy & Neuorbiology, Univ California Irvine, Irvine, CA, 6Dept Psych & Hum Behav, Univ California Irvine, Irvine, CA.
Reductions in trophic support may contribute to deficits in synaptic plasticity and cognitive function that arise with age. Previous studies have shown that in the rat hippocampal CA1 basal dendritic field, deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested if increasing endogenous Brain Derived Neurotrophic Factor (BDNF) levels could reverse this age-related change. Middle-aged (8-10 mo) Sprague Dawley rats were administered a short-lived, positive AMPA-type glutamate receptor modulator (ampakine) systemically twice-daily for 4 days and were sacrificed for electrophysiological (hippocampal slice) and neurochemical (ELISA, Western blot) analyses 18 hrs after the last injection. Ampakine treatment significantly increased mature BDNF protein levels in hippocampus. This effect was accompanied by a restoration of LTP stabilization in the CA1 basal dendritic field. The rescue of enduring LTP was not due to acute effects of the drug (half-life <30 min) or to enhanced synaptic transmission (input-output curves and baseline fEPSPs did not differ between ampakine- and vehicle-treated rats). Bath administration of the extracellular BDNF scavenger TrkB-Fc to hippocampal slices completely eliminated the restoration of basal dendritic LTP in experimental rats but had no effect on LTP in this field in middle aged, vehicle-control animals. These results indicate that ampakine-induced increases in BDNF signaling offset age-related deficits in processes that stabilize LTP and suggest the possibility that intermittent, in vivo ampakine treatments might ameliorate deficits in synaptic plasticity and cognitive function with aging. <<<
