Calcium chelation improves spatial learning and synaptic plasticity in aged rats.
Impaired regulation of intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. Comparing young (2-3 months) and aged (23-26 months) Fisher 344 rats, stratum radiatum-evoked CA1 field EPSPs were smaller and long-term potentiation (LTP) was diminished in aged hippocampal slices. Resting calcium, in presynaptic axonal terminals in the CA1 stratum radiatum area, was elevated in aged slices. Loading the slice with the calcium chelator, BAPTA-AM, depressed LTP in young slices, but enhanced this plasticity in old slices. Forty-five minutes following LTP-inducing high frequency stimulation, resting calcium levels were significantly increased in both young and old presynaptic terminals, and significantly reduced by pretreatment with BAPTA-AM. In vivo, intraperitoneal administration of BAPTA-AM prior to training in the reference memory version of the Morris water maze test, significantly improved the acquisition of spatial learning in aged animals, without a significant effect in young rats. These results support the hypothesis that increasing intracellular neuronal buffering power for calcium in aged rats ameliorates age-related impaired synaptic plasticity and learning.
Tonkikh
Alexander
A
Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
Janus
Christopher
C
El-Beheiry
Hossam
H
Pennefather
Peter S
PS
Samoilova
Marina
M
McDonald
Patrick
P
Ouanounou
Aviv
A
Carlen
Peter L
PL
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002614:Chelating Agents; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium