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 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.
D'Intino
Giulia
G
Department of Veterinary Morphophysiology and Animal Production, University of Bologna, 40064 Ozzano Emilia (Bologna), Italy.
Paradisi
Michela
M
Fernandez
Mercedes
M
Giuliani
Alessandro
A
Aloe
Luigi
L
Giardino
Luciana
L
Calzà
Laura
L
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003072:Cognition Disorders / Q000209:etiology*; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D018782:Maze Learning; D008568:Memory; D009103:Multiple Sclerosis / Q000188:drug therapy; D009186:Myelin Sheath / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D016548:Prosencephalon / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew
D002800:Cholinesterase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase