Cognitive Deficit Associated with Cholinergic and Nerve Growth Factor Down-Regulation in Experimental Allergic Encephalomyelitis in Rats

Clinical symptoms in multiple sclerosis include cognitive dysfunction. Difficulties in learning and remembering new information represent the most common cognitive deficit and are associated with a general and progressive brain pathology. Possible pathogenetic mechanisms for neuronal damage such as...

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Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS 2005-02, Vol.102 (8), p.3070-3075
Main Authors:	D'Intino, Giulia, Paradisi, Michela, Fernandez, Mercedes, Giuliani, Alessandro, Aloe, Luigi, Giardino, Luciana, Calzà, Laura, Levi-Montalcini, Rita
Format:	Article
Language:	eng
Subjects:	Animals Biochemistry Biological Sciences Brain Cerebral cortex Choline O-Acetyltransferase - metabolism Cholinergics Cholinesterase Inhibitors - pharmacology Cognition & reasoning Cognition Disorders - etiology Down-Regulation Encephalomyelitis, Autoimmune, Experimental - complications Encephalomyelitis, Autoimmune, Experimental - metabolism Female Forebrain Gene expression Gene Expression Regulation Glial Fibrillary Acidic Protein - analysis Maze Learning Mazes Memory Messenger RNA Multiple Sclerosis - drug therapy Myelin Sheath - metabolism Nerve Growth Factor - genetics Nervous system diseases Neurology Neurons Neuroprotective Agents - therapeutic use Prosencephalon - physiology Rats Rats, Inbred Lew Ribonucleic acid RNA RNA, Messenger - analysis
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Summary:	Clinical symptoms in multiple sclerosis include cognitive dysfunction. Difficulties in learning and remembering new information represent the most common cognitive deficit and are associated with a general and progressive brain pathology. Possible pathogenetic mechanisms for neuronal damage such as neuroprotective strategies are under active investigation also in experimental allergic encephalomyelitis, the most widely used experimental model for multiple sclerosis. In this paper we demonstrate that a selective deficit in learning and memory performance, as investigated by the Morris water maze test, is a consistent feature in rat encephalomyelitis, which correlates with a decline in choline acetyltransferase activity and nerve growth factor mRNA level in cerebral cortex, hippocampus, and basal forebrain. Treatment aimed to restore acetylcholine content through chronic administration of selective acetylcholinesterase inhibitors (rivastigmine and donepezil) restores cognitive performance, choline acetyltransferase activity, and nerve growth factor mRNA expression.
ISSN:	0027-8424 1091-6490