TY - JOUR
T1 - Reduced choline acetyltransferase activity and muscarinic M1 receptor levels in aged Fisher 344 rat brains did not parallel their respective mRNA levels
AU - Ogawa, Norio
AU - Asanuma, Masato
AU - Kondo, Yoichi
AU - Nishibayashi, Sakiko
AU - Mori, Akitane
PY - 1994
Y1 - 1994
N2 - Differences in the acetylcholine (ACh)-mediated neuronal system of the brain between aged and young rats were studied by measuring choline acetyltransferase (ChAT) activity, muscarinic M1 receptor (M1-R) and their respective mRNA levels. In aged rats, ChAT activity and the M1-R level were significantly reduced in the cerebral cortex, hippocampus and striatum compared with that in young rats. On the other hand, there was no difference in the ChAT mRNA level in the striatum and the basal forebrain, or the M1-R mRNA level in the cerebral cortex, hippocampus and striatum between aged and young rats. The effects of chronic administration of bifemelane (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride), which is used for the treatment of sequelae of cerebrovascular diseases, were also evaluated. In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum. However, the ChAT mRNA level and the M1-R mRNA level were not affected by bifemelane administration. Thus, the decreases and recoveries in ChAT activity and M1-R level did not parallel the changes in their respective mRNAs. These results suggest that the age-related impairments in ACh-mediated neuronal system are considered to be caused primarily by disorders of post-transcriptional events.
AB - Differences in the acetylcholine (ACh)-mediated neuronal system of the brain between aged and young rats were studied by measuring choline acetyltransferase (ChAT) activity, muscarinic M1 receptor (M1-R) and their respective mRNA levels. In aged rats, ChAT activity and the M1-R level were significantly reduced in the cerebral cortex, hippocampus and striatum compared with that in young rats. On the other hand, there was no difference in the ChAT mRNA level in the striatum and the basal forebrain, or the M1-R mRNA level in the cerebral cortex, hippocampus and striatum between aged and young rats. The effects of chronic administration of bifemelane (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride), which is used for the treatment of sequelae of cerebrovascular diseases, were also evaluated. In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum. However, the ChAT mRNA level and the M1-R mRNA level were not affected by bifemelane administration. Thus, the decreases and recoveries in ChAT activity and M1-R level did not parallel the changes in their respective mRNAs. These results suggest that the age-related impairments in ACh-mediated neuronal system are considered to be caused primarily by disorders of post-transcriptional events.
KW - Aged rat brain
KW - Bifemelane hydrochloride
KW - ChAT mRNA
KW - Choline acetyltransferase (ChAT)
KW - M1-R mRNA
KW - Muscarinic M1 receptor (M1-R)
KW - Parallelism
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U2 - 10.1016/S0006-8993(09)90013-0
DO - 10.1016/S0006-8993(09)90013-0
M3 - Article
C2 - 7834359
AN - SCOPUS:0028120409
VL - 658
SP - 87
EP - 92
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -