Alterations in the balance of protein kinase/phosphatase activities parallel reduced synaptic strength during aging.
The current research examined the regulation of synaptic strength by protein phosphorylation during aging. Bath application of the protein phosphatase 1 and 2A (PP1 and PP2A) inhibitor calyculin A (1 microM) enhanced CA3-CA1 synaptic strength in hippocampal slices from aged male (20-24 mo) but not from young adult male (4-6 mo) Fischer 344 rats. Similarly, injection of the PP1 and PP2A inhibitor microcystin-L,R (5 microM) into CA1 cells caused an increase in the intracellular synaptic response only in slices from aged rats. In contrast, bath application of the serine/threonine kinase inhibitor H-7 (10 microM) induced a decrease in synaptic strength only in slices from the young adult group. These results demonstrate that phosphorylation dependent regulation of intrinsic synaptic efficacy changes during aging.
Norris
C M
CM
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536, USA.
Halpain
S
S
Foster
T C
TC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D009924:Organ Culture Techniques; D010080:Oxazoles / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D054645:Protein Phosphatase 1; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000201:enzymology*
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010080:Oxazoles; D010456:Peptides, Cyclic; C078588:microcystin; C059041:calyculin A; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1