Spatial memory in aged rats is related to PKCgamma-dependent G-protein coupling of the M1 receptor.
In the present study, individual differences in spatial memory in aged Fischer 344 (F344) rats were associated with the extent of G-protein coupling of the M1 muscarinic receptor and the dendritic-to-somal ratio of hippocampal PKCgamma (d/sPKCgamma) immunogenicity. Following testing in the eight-arm radial maze task, 7 young and 13 aged rat brains were sectioned through the dorsal hippocampal formation (HF). G-protein coupling of the M1 receptor was assessed autoradiographically using competition binding studies in the presence and absence of a G-protein uncoupler to determine high (K(H)) and low (K(L)) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and K(H), a measure of M1 receptor-G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCgamma immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between K(H) and d/sPKCgamma. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCgamma signal transduction is associated with spatial memory dysfunction.
Rossi
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MA
Department of Neurological Sciences, Rush University Medical Center, Suite 334 Murdoch Building, 1653 West Congress Parkway, Chicago, IL 60612, USA. mrossi@palm.net
Mash
D C
DC
deToledo-Morrell
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L
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001667:Binding, Competitive / Q000502:physiology; D002217:Carbachol / Q000493:pharmacokinetics; D002452:Cell Count; D002755:Choice Behavior / Q000187:drug effects; D018679:Cholinergic Agonists / Q000493:pharmacokinetics; D003712:Dendrites / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000493:pharmacokinetics; D011493:Protein Kinase C / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D043643:Receptor, Muscarinic M1 / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology*; D014316:Tritium / Q000493:pharmacokinetics
D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D014316:Tritium; D010890:Pirenzepine; D002217:Carbachol; C087857:protein kinase C gamma; D011493:Protein Kinase C