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NEUROPHARMACOLOGY

An Electrophysiological Model of Spinal Transmission Deficits in Mouse Experimental Autoimmune Encephalomyelitis

CNS Pharmacology, Aventis Pharmaceuticals, Inc., Bridgewater, New Jersey

Chronic relapsing/remitting experimental autoimmune encephalomyelitis (EAE) can be induced in 8-week-old female SJL/J(H-2) mice via inoculation with the p139-151 peptide of myelin proteolipid protein (PLP), Mycobacterium tuberculosis (MT), complete Freund's adjuvant (CFA), and Bordatella pertussis. EAE is a relevant preclinical model of MS that incorporates several aspects of the clinical disease. Chief among these are the inflammatory mediated neurological deficits. While the impact of localized spinal cord demyelination on neurotransmission has been modeled successfully, relatively little work has been done with spinal cord from animals with EAE. The goal of this study was to assess the utility of a grease-gap tissue bath methodology in the detection of transmission deficits in EAE spinal cord tissue. Spinal cords removed from EAE mice at different phases of the neurological deficit were assessed for their response to both lumbar and sacral application of one of several depolarizing agents (veratridine, potassium chloride [KCl], (±)--amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA]). The main finding of this study is that transmission deficits were detected in EAE mice at the onset of the neurological deficits. They were sustained for a period of approximately 2 to 3 weeks post disease onset followed by a gradual recovery of group function. The other finding is that there is a decrease in the latency to achieve AMPA-mediated depolarization in sacral spinal cord that is independent of the magnitude of the depolarization response. These results suggest that this methodology can be utilized to assess sensory and motor deficits in spinal cord from EAE animals.

Address correspondence to: Dr. Susan E. Hanak, CNS Pharmacology, Aventis Pharmaceuticals, Inc., P.O. Box 6800, Building: JR2-3204D; mailstop: JR2-303A, Bridgewater, NJ 08807. E-mail: Susan.Hanak{at}aventis.com

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