Calcium chelation improves spatial learning and synaptic plasticity in aged rats

• Published in: Experimental neurology Vol. 197; no. 2; pp. 291 - 300
• Main Authors: Tonkikh, Alexander, Janus, Christopher, El-Beheiry, Hossam, Pennefather, Peter S., Samoilova, Marina, McDonald, Patrick, Ouanounou, Aviv, Carlen, Peter L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2006; Elsevier
• Subjects: Aging; Aging - physiology; Analysis of Variance; Animals; Behavior, Animal; Biological and medical sciences; Calcium - metabolism; Calcium regulation; Chelating Agents - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Electric Stimulation - methods; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Excitatory Postsynaptic Potentials - radiation effects; Hippocampus - cytology; In Vitro Techniques; Injuries of the nervous system and the skull. Diseases due to physical agents; Learning - drug effects; Learning - physiology; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - drug effects; Neurons - physiology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Inbred F344; Reaction Time - drug effects; Spatial Behavior - drug effects; Spatial Behavior - physiology; Spatial learning; Synaptic plasticity; Time Factors; Traumas. Diseases due to physical agents; Aging; Spatial learning; Synaptic plasticity; Calcium regulation; Potentiation; Senescence; Intraperitoneal administration; Calcium; Rat; Memory; Rodentia; Central nervous system; Cognition; Encephalon; Learning; Vertebrata; Mammalia; Acquisition process; Animal; Intracellular; Pretreatment; High frequency; Hippocampus; Presynaptic
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2005.06.014

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.