Chronic administration of acetylcholinesterase inhibitor in the senescent rat brain.
The effects of chronic administration of ENA-713, an acetylcholinesterase (AChE) inhibitor, on pre- and postsynaptic cholinergic indices were examined in the senescent rat brain. In the senescent group, the acetylcholine (ACh) level was markedly reduced in the frontal cortex, hippocampus, striatum and thalamus+midbrain, but these reductions were completely prevented by ENA-713. Moreover, although choline acetyltransferase (ChAT) activity was also significantly decreased in these four regions, it recovered in the frontal cortex, hippocampus and thalamus+midbrain after ENA-713 treatment. In contrast, cholinesterase (ChE) activity was not changed in any experimental groups. The maximum number (Bmax) of muscarinic M1 receptor (M1-R) binding site in the frontal cortex in the senescent group was decreased without any change in affinity, but this decrease was also inhibited by ENA-713. Thus, these findings suggest that ENA-713 may have protective, neurotrophic and therapeutic effects on aging-induced cholinergic dysfunction and be useful for the treatment of aging-related dementia, such as the Alzheimer-type dementia.
Tanaka
K
K
Department of Neuroscience, Okayama University Medical School, Japan.
Ogawa
N
N
Asanuma
M
M
Kondo
Y
Y
Mori
A
A
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002219:Carbamates / Q000008:administration & dosage* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D048448:Phenylcarbamates; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D000068836:Rivastigmine
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D000068836:Rivastigmine