Cholinergic imbalance in the multiple sclerosis hippocampus

Evert-Jan Kooi, Marloes Prins, Natasha Bajic, Jeroen A M Beliën, Wouter H Gerritsen, Jack van Horssen, Eleonora Aronica, Anne-Marie van Dam, Jeroen J M Hoozemans, Paul T Francis, Paul van der Valk, Jeroen J G Geurts

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Abstract

Hippocampal pathology was shown to be extensive in multiple sclerosis (MS) and is associated with memory impairment. In this post-mortem study, we investigated hippocampal tissue from MS and Alzheimer's disease (AD) patients and compared these to non-neurological controls. By means of biochemical assessment, (immuno)histochemistry and western blot analyses, we detected substantial alterations in the cholinergic neurotransmitter system in the MS hippocampus, which were different from those in AD hippocampus. In MS hippocampus, activity and protein expression of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was decreased, while the activity and protein expression of acetylcholinesterase (AChE), the acetylcholine degrading enzyme, was found to be unaltered. In contrast, in AD hippocampus both ChAT and AChE enzyme activity and protein expression was decreased. Our findings reveal an MS-specific cholinergic imbalance in the hippocampus, which may be instrumental in terms of future treatment options for memory problems in this disease.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalActa Neuropathologica
Volume122
Issue number3
DOIs
Publication statusPublished - Sep 2011

Cite this

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title = "Cholinergic imbalance in the multiple sclerosis hippocampus",
abstract = "Hippocampal pathology was shown to be extensive in multiple sclerosis (MS) and is associated with memory impairment. In this post-mortem study, we investigated hippocampal tissue from MS and Alzheimer's disease (AD) patients and compared these to non-neurological controls. By means of biochemical assessment, (immuno)histochemistry and western blot analyses, we detected substantial alterations in the cholinergic neurotransmitter system in the MS hippocampus, which were different from those in AD hippocampus. In MS hippocampus, activity and protein expression of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was decreased, while the activity and protein expression of acetylcholinesterase (AChE), the acetylcholine degrading enzyme, was found to be unaltered. In contrast, in AD hippocampus both ChAT and AChE enzyme activity and protein expression was decreased. Our findings reveal an MS-specific cholinergic imbalance in the hippocampus, which may be instrumental in terms of future treatment options for memory problems in this disease.",
keywords = "Acetylcholinesterase, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Choline O-Acetyltransferase, Female, Hippocampus, Humans, Male, Middle Aged, Multiple Sclerosis, Journal Article, Research Support, Non-U.S. Gov't",
author = "Evert-Jan Kooi and Marloes Prins and Natasha Bajic and Beli{\"e}n, {Jeroen A M} and Gerritsen, {Wouter H} and {van Horssen}, Jack and Eleonora Aronica and {van Dam}, Anne-Marie and Hoozemans, {Jeroen J M} and Francis, {Paul T} and {van der Valk}, Paul and Geurts, {Jeroen J G}",
year = "2011",
month = "9",
doi = "10.1007/s00401-011-0849-4",
language = "English",
volume = "122",
pages = "313--322",
journal = "Acta Neuropathologica",
issn = "0001-6322",
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Cholinergic imbalance in the multiple sclerosis hippocampus. / Kooi, Evert-Jan; Prins, Marloes; Bajic, Natasha; Beliën, Jeroen A M; Gerritsen, Wouter H; van Horssen, Jack; Aronica, Eleonora; van Dam, Anne-Marie; Hoozemans, Jeroen J M; Francis, Paul T; van der Valk, Paul; Geurts, Jeroen J G.

In: Acta Neuropathologica, Vol. 122, No. 3, 09.2011, p. 313-322.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Cholinergic imbalance in the multiple sclerosis hippocampus

AU - Kooi, Evert-Jan

AU - Prins, Marloes

AU - Bajic, Natasha

AU - Beliën, Jeroen A M

AU - Gerritsen, Wouter H

AU - van Horssen, Jack

AU - Aronica, Eleonora

AU - van Dam, Anne-Marie

AU - Hoozemans, Jeroen J M

AU - Francis, Paul T

AU - van der Valk, Paul

AU - Geurts, Jeroen J G

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N2 - Hippocampal pathology was shown to be extensive in multiple sclerosis (MS) and is associated with memory impairment. In this post-mortem study, we investigated hippocampal tissue from MS and Alzheimer's disease (AD) patients and compared these to non-neurological controls. By means of biochemical assessment, (immuno)histochemistry and western blot analyses, we detected substantial alterations in the cholinergic neurotransmitter system in the MS hippocampus, which were different from those in AD hippocampus. In MS hippocampus, activity and protein expression of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was decreased, while the activity and protein expression of acetylcholinesterase (AChE), the acetylcholine degrading enzyme, was found to be unaltered. In contrast, in AD hippocampus both ChAT and AChE enzyme activity and protein expression was decreased. Our findings reveal an MS-specific cholinergic imbalance in the hippocampus, which may be instrumental in terms of future treatment options for memory problems in this disease.

AB - Hippocampal pathology was shown to be extensive in multiple sclerosis (MS) and is associated with memory impairment. In this post-mortem study, we investigated hippocampal tissue from MS and Alzheimer's disease (AD) patients and compared these to non-neurological controls. By means of biochemical assessment, (immuno)histochemistry and western blot analyses, we detected substantial alterations in the cholinergic neurotransmitter system in the MS hippocampus, which were different from those in AD hippocampus. In MS hippocampus, activity and protein expression of choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was decreased, while the activity and protein expression of acetylcholinesterase (AChE), the acetylcholine degrading enzyme, was found to be unaltered. In contrast, in AD hippocampus both ChAT and AChE enzyme activity and protein expression was decreased. Our findings reveal an MS-specific cholinergic imbalance in the hippocampus, which may be instrumental in terms of future treatment options for memory problems in this disease.

KW - Acetylcholinesterase

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Choline O-Acetyltransferase

KW - Female

KW - Hippocampus

KW - Humans

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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JO - Acta Neuropathologica

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