Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients

Ezra Mulugeta; Evert Karlsson; Atiqul Islam; Raj Kalaria; Halinder Mangat; Bengt Winblad; Abdu Adem

doi:10.1016/S0006-8993(02)03542-4

Loss of muscarinic M₄ receptors in hippocampus of Alzheimer patients

Ezra Mulugeta, Evert Karlsson, Atiqul Islam, Raj Kalaria, Halinder Mangat, Bengt Winblad, Abdu Adem

Research output: Contribution to journal › Article › peer-review

73 Citations (Scopus)

Abstract

We assessed muscarinic M₁, M₂ and M₄ receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [¹²⁵I]muscarinic toxin-1 ([¹²⁵I]MT-1, M₁ selective), [³H]AFDX-384 (M₂ partially selective) and [¹²⁵I]muscarinic toxin 4 ([¹²⁵I]M₄ toxin-1, M₄ selective). Our results revealed a significant decrease in muscarinic M₄ receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M₁ or M₂ receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M₄ receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).

Original language	English
Pages (from-to)	259-262
Number of pages	4
Journal	Brain Research
Volume	960
Issue number	1-2
DOIs	https://doi.org/10.1016/S0006-8993(02)03542-4
Publication status	Published - Jan 17 2003

Keywords

Alzheimer's disease
Hippocampus
Mamba toxin
Muscarinic receptor

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

Access to Document

10.1016/S0006-8993(02)03542-4

Cite this

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title = "Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients",

abstract = "We assessed muscarinic M1, M2 and M4 receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [125I]muscarinic toxin-1 ([125I]MT-1, M1 selective), [3H]AFDX-384 (M2 partially selective) and [125I]muscarinic toxin 4 ([125I]M4 toxin-1, M4 selective). Our results revealed a significant decrease in muscarinic M4 receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M1 or M2 receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M4 receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).",

keywords = "Alzheimer's disease, Hippocampus, Mamba toxin, Muscarinic receptor",

author = "Ezra Mulugeta and Evert Karlsson and Atiqul Islam and Raj Kalaria and Halinder Mangat and Bengt Winblad and Abdu Adem",

note = "Funding Information: We are grateful to Dr. Adlan Elhasan and Dr. Gunnar Johansson for their helpful discussions and to Dr. Allan E. Johnson for valuable methodological discussions and language correction. These experiments were supported by grants from the European Union (QLK6-CT-1999-02112), the Swedish Medical Council and Alzheimerfonden to A. Adem and E. Karlsson. Preliminary results of these studies were reported previously [1] .",

year = "2003",

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T1 - Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients

AU - Mulugeta, Ezra

AU - Karlsson, Evert

AU - Islam, Atiqul

AU - Kalaria, Raj

AU - Mangat, Halinder

AU - Winblad, Bengt

AU - Adem, Abdu

N1 - Funding Information: We are grateful to Dr. Adlan Elhasan and Dr. Gunnar Johansson for their helpful discussions and to Dr. Allan E. Johnson for valuable methodological discussions and language correction. These experiments were supported by grants from the European Union (QLK6-CT-1999-02112), the Swedish Medical Council and Alzheimerfonden to A. Adem and E. Karlsson. Preliminary results of these studies were reported previously [1] .

PY - 2003/1/17

Y1 - 2003/1/17

N2 - We assessed muscarinic M1, M2 and M4 receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [125I]muscarinic toxin-1 ([125I]MT-1, M1 selective), [3H]AFDX-384 (M2 partially selective) and [125I]muscarinic toxin 4 ([125I]M4 toxin-1, M4 selective). Our results revealed a significant decrease in muscarinic M4 receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M1 or M2 receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M4 receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).

AB - We assessed muscarinic M1, M2 and M4 receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [125I]muscarinic toxin-1 ([125I]MT-1, M1 selective), [3H]AFDX-384 (M2 partially selective) and [125I]muscarinic toxin 4 ([125I]M4 toxin-1, M4 selective). Our results revealed a significant decrease in muscarinic M4 receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M1 or M2 receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M4 receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).

KW - Alzheimer's disease

KW - Hippocampus

KW - Mamba toxin

KW - Muscarinic receptor

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