Change of central cholinergic receptors following lesions of nucleus basalis magnocellularis in rats: search for an imaging index suitable for the early detection of Alzheimer's disease.
Cholinergic system in the central nervous system is involved in the memory function. Thus, because the dysfunction of cholinergic system that project to the cerebral cortex from nucleus basalis of Meynert (nbM) would be implicated in the memory function deficits in Alzheimer's disease (AD), evaluating cholinergic function may be useful for the early detection of AD. In this study, because the nucleus basalis magnocellularis (NBM) in rats is equivalent to nbM in human, we investigated the change in cholinergic receptors in the frontal cortex of rats with unilateral lesion to the NBM to find an appropriate index for the early detection of AD using techniques of nuclear medicine. The right NBM was injected with ibotenic acid. [(18)F]FDG-PET images were obtained 3 days later. Some rats were sacrificed at 1 week, whereas others were subjected to a second [(18)F]FDG-PET at 4 weeks then sacrificed for membrane preparation. The prepared membranes were subjected to radioreceptor assays to measure the density of nicotinic and muscarinic acetylcholine receptors. Glucose metabolism had decreased on the damaged side compared to the control side at 3 days, but at 4 weeks, there was no difference between the sides. Nicotinic acetylcholine receptors had significantly decreased in density compared to the control side at both 1 and 4 weeks. However, muscarinic receptors were not affected. These results suggested that neuronal dysfunction in AD could be diagnosed at an early stage by imaging nicotinic acetylcholine receptors.
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Mikako
M
Ogawa
Yasuhiko
Y
Iida
Masaki
M
Nakagawa
Yugi
Y
Kuge
Hidekazu
H
Kawashima
Akiko
A
Tominaga
Masashi
M
Ueda
Yasuhiro
Y
Magata
Hideo
H
Saji
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005625:Frontal Lobe / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012720:Severity of Illness Index; D014018:Tissue Distribution
D015415:Biomarkers; D019275:Radiopharmaceuticals; D011950:Receptors, Cholinergic; D019788:Fluorodeoxyglucose F18