Learning deficiency and alterations in acetylcholine receptors and protein kinase C in the brain of senescence-accelerated mouse (SAM)-P10.
The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. A novel inbred SAMP10 has shown age-related brain atrophy and learning deficiency. In the present study, we investigated the changes in learning ability and in ligand binding with muscarinic acetylcholine (mACh) receptors, alpha adrenoceptors and protein kinase C in SAMP10. In Morris's water maze task, in a control strain of SAMR1 at 9 months, the escape latency and path length decreased with increasing trial days, in contrast, escape latency and path length did not decrease in SAMP10. These results indicate that SAMP10 exhibits learning deficiency. The ligand binding activity of mACh receptors decreased in the hippocampus of SAMP10 and the protein kinase C level in the hippocampus of SAMP10 was lower than that of SAMR1. On the other hand, there was no significant difference between SAMR1 and SAMP10 regarding ligand binding activity of alpha(1) and alpha(2) adrenoceptors. Thus, a reduction of mACh receptors and protein kinase C in the brain seems to underlie dysfunction of learning and memory in SAMP10.
Okuma
Y
Y
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Murayama
T
T
Tha
K K
KK
Yamada
C
C
Hosokawa
M
M
Ishikawa
A
A
Watanabe
R
R
Maekawa
M
M
Nomura
Y
Y
D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D007859:Learning Disabilities / Q000523:psychology*; D008024:Ligands; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D009043:Motor Activity / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*
D008024:Ligands; D011950:Receptors, Cholinergic; D011493:Protein Kinase C