Short report
Alterations of muscarinic acetylcholine receptor subtypes in
diffuse Lewy body disease: relation to Alzheimer's disease
Kazumasa Shiozakia, Eizo Isekia, Haruaki Uchiyamab, Yasuhiro Watanabec, Tatsuya Hagad, Kimihiko Kameyamad, Tomoaki Ikedae, Takayuki Yamamotoe, Kenji Kosakaa
a Department of
Psychiatry, Yokohama City University, School of Medicine, 3-9 Fukuura,
Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan, b Department of
Neurosurgery, Hamamatsu Red Cross Hospital, 1-5-30 Takabayashi,
Hamamatsu, Shizuoka 430-0907, Japan, c Department of Pharmacology, National Defense
Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-0042, Japan, d Department
of Neurochemistry, Faculty of Medicine, University of Tokyo, 7-3-1
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, e Fukushimura Hospital, 19-14 Yamanaka,
Noyori-cho, Toyohashi, Aichi 441-8124, Japan
Correspondence to: Dr Kazumasa Shiozaki, Department of Psychiatry, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Fax 0081 45 783 2540; email: NBG01035{at}nifty.ne.jp
Received 11 August
1998 and in revised form 17 February 1999;
Accepted 23
February 1999
OBJECTIVES
Dementia
associated with Lewy bodies in cortical and subcortical areas is
classified as dementia of the non-Alzheimer type and termed diffuse
Lewy body disease (DLBD). The generic term "dementia with Lewy bodies
(DLB)" was proposed in the international workshop on Lewy body
dementia to include the similar disorders presenting Lewy bodies. In
DLB, a lower level of choline acetyltransferase (ChAT) activity in the
neocortex was found compared with that in Alzheimer's disease. The
purpose of the present study was to determine the total amount of
muscarinic acetylcholine receptors (mAChRs) and relative proportion of
each subtype (m1-m4) of mAChRs in the frontal and temporal cortex of
seven DLBD and 11 Alzheimer's disease necropsied brains.
METHODSA
[3H]quinuclidinyl benzilate (QNB) binding assay and an
immunoprecipitation assay using subtype-specific antibodies were
performed. Each antibody was raised against fusion proteins containing
peptides corresponding to the third intracellular (i3) loops of the
respective mAChR subtype.
RESULTSThe total
amounts of mAChRs were significantly lower in the preparations of
temporal cortices from DLBD and Alzheimer's disease than in those from
dead controls (seven cases). In both diseases, the proportion of the m3
receptor in the frontal cortex was significantly increased and that of
the m4 receptor in the temporal cortex was significantly decreased
compared with the control specimens. The proportions of the m1 and m2
subtypes were significantly different in the temporal cortex. The
proportion of the m1 receptor was significantly greater in the DLBD
brains, whereas that of the m2 receptor was significantly greater in
the Alzheimer's disease brains than in the controls.
CONCLUSIONSThe m1
receptor is the major subtype in the cerebral cortex, and m2 is known
to be present at presynaptic terminals. The higher proportions of m1 in
DLBD and m2 in Alzheimer's disease suggest that the manner of degeneration in the cholinergic system is different between the diseases. It is hypothesised that a severe depletion of
presynaptic cholinergic projective neurons causes the upregulation of
m1 receptor in the temporal cortex in DLBD.
Keywords: muscarinic receptor; subtype specific antibody; diffuse lewy body disease; cholinergic deficit
© 1999 by Journal of Neurology, Neurosurgery, and Psychiatry
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
-
Bhanji, N. H., Gauthier, S.
(2005). Emergent Complications Following Donepezil Switchover to Galantamine in Three Cases of Dementia With Lewy Bodies. J. Neuropsychiatry Clin. Neurosi.
17: 552-555
[Abstract] [Full Text] -
Simard, M., van Reekum, R.
(2004). The Acetylcholinesterase Inhibitors for Treatment of Cognitive and Behavioral Symptoms in Dementia With Lewy Bodies. J. Neuropsychiatry Clin. Neurosi.
16: 409-425
[Abstract] [Full Text] -
Odawara, T, Shiozaki, K, Iseki, E, Hino, H, Kosaka, K
(2003). Alterations of muscarinic acetylcholine receptors in atypical Pick's disease without Pick bodies. J. Neurol. Neurosurg. Psychiatry
74: 965-967
[Abstract] [Full Text] -
Rho, J. M., Storey, T. W.
(2001). Molecular Ontogeny of Major Neurotransmitter Receptor Systems in the Mammalian Central Nervous System: Norepinephrine, Dopamine, Serotonin, Acetylcholine, and Glycine. J Child Neurol
16: 271-280
[Abstract] -
JELLINGER, K. A
(2000). Alterations of muscarinic acetylcholine receptor subypes in diffuse Lewy body disease: relation to Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry
68: 253-254
[Full Text]
- Full Text
- Full Text (PDF)
- Submit a response
- Alert me when this article is cited
- Alert me when eLetters are posted
- Alert me if a correction is posted
- Citation Map
Services
- Email this link to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Add article to my folders
- Download to citation manager
- Request Permissions
Citing Articles
Google Scholar
PubMed
Topic Collections
-
Memory disorders (neurology)
-
Drugs: CNS (not psychiatric)
-
Parkinson's disease
-
Memory disorders (psychiatry)
- Psychiatry of old age
Bookmark with
Register for free content
The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.
Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.
