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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Cholinergic imbalance in the multiple sclerosis hippocampus
Evert-Jan Kooi1, Marloes Prins, Natasha Bajic
1Department of Pathology (Neuropathology), VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. e.kooi@vumc.nl
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.
Insights
Multiple sclerosis (MS) patients show an MS-specific imbalance in the hippocampus
Area of Science:
- Neuroscience
- Neurochemistry
Background:
- Hippocampal pathology is extensive in multiple sclerosis (MS), contributing to memory impairment.
- Alzheimer's disease (AD) also affects the hippocampus, but with different pathological mechanisms.
Purpose of the Study:
- To investigate and compare the cholinergic system in the hippocampus of MS patients versus AD patients and controls.
- To identify potential therapeutic targets for memory deficits in MS.
Main Methods:
- Post-mortem analysis of hippocampal tissue.
- Biochemical assays, immunohistochemistry, and Western blot analyses were employed.
Main Results:
- MS hippocampus exhibited decreased choline acetyltransferase (ChAT) activity and protein, with unaltered acetylcholinesterase (AChE).
- AD hippocampus showed decreased activity and protein for both ChAT and AChE.
- These findings indicate an MS-specific cholinergic imbalance in the hippocampus.
Conclusions:
- The observed cholinergic imbalance in the MS hippocampus is distinct from that in AD.
- This MS-specific alteration may offer novel therapeutic avenues for managing memory problems in multiple sclerosis.
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