Variations in excitatory and inhibitory postsynaptic protein content in rat cerebral cortex with respect to aging and cognitive status.
Age-related cognitive impairments are associated with structural and functional changes in the cerebral cortex. We have previously demonstrated in the rat that excitatory and inhibitory pre- and postsynaptic changes occur with respect to age and cognitive status; however, in aged cognitively impaired animals, we have shown a significant imbalance in postsynaptic markers of excitatory versus inhibitory synapses, using markers of excitatory versus inhibitory neurotransmitter-related scaffolding proteins [postsynaptic density-95 (PSD95)/synapse associated protein-90 (SAP90) and gephyrin, respectively]. The present study focuses on whether the expression of various excitatory and inhibitory postsynaptic proteins is affected by ageing and cognitive status. Thus, aged animals were segregated into aged cognitively impaired (AI) and aged cognitively unimpaired (AU) groups using the Morris water maze. We applied Western immunoblotting to reveal the expression patterns of a number of relevant excitatory and inhibitory receptors in the prefrontal and parietal cortices of young (Y), AU and AI animals, and performed semi-quantitative analyses to statistically tabulate changes among the three animal groups. A significant increase in the inhibitory postsynaptic scaffold protein, gephyrin, was observed in the parietal cortex of AI animals. Similarly, an increase in GABA(A) receptor subunit alpha1 was observed in the parietal cortex of AI animals. An increase in the excitatory N-methyl-d-aspartate receptor subunit N-methyl-d-aspartate receptor 1 expression was observed in the parietal cortex of AI animals, whereas a significant decrease in AMPA receptor subunit glutamate receptor 2 expression was found in the prefrontal cortex of AI animals. Finally, the excitatory, postsynaptic neuronal cell-adhesion receptor, neuroligin-1, was found to be significantly increased in both the prefrontal and parietal cortical areas of AI animals.
Majdi
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Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1325, Montreal, Quebec, Canada H3G 1Y6.
Ribeiro-da-Silva
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Cuello
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D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; C073441:gephyrin; C093438:neuroligin 1; C104722:glutamate receptor ionotropic, AMPA 2