INVOLVEMENT OF THE GABAERGIC SYSTEM IN THE INDUCTION OF THE NEUROPATHOLOGICAL ALTERATIONS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE).

NICOLÁS FERNÁNDEZ HURST, MARIO J. BIBOLINI, NATALÍ L. CHANADAY, CLARA G. MONFERRAN, AND GERMAN A. ROTH

Huerta Grande. Córdoba.

Congreso; XXVI Reunión Anual de la Sociedad Argentina de Neurociencias; 2011

Sociedad Argentina de Investigación en Neurociencias

INVOLVEMENT OF THE GABAERGIC SYSTEM IN THE INDUCTION OF THE NEUROPATHOLOGICAL ALTERATIONS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE).

 

Nicolás Fernández Hurst, Mario J. Bibolini, Natalí L. Chanaday, Clara G. Monferran, and German A. Roth

 

Departamento de Química Biológica-CIQUIBIC. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina.

 

EAE is an inflammatory and demyelinating disease used as model of multiple sclerosis, which is characterized by a strong cellular response against myelin antigens and neuronal compromise. In order to better understand the events that lead to the progressive neuronal dysfunction, we previously explored the contribution of glutamate release in frontal cerebral cortex from rats with EAE. We found a significant decrease of glutamate release regulated by GABA from synaptosomes of EAE rats during the acute stage of the disease. In order to determinate the GABA system participation in EAE progression, now we evaluated the effect of GABAergic agents with different action mechanisms on disease induction, proliferation of T cells, and glutamate release. The results indicate that meanwhile treatment of rats post-EAE induction with GABA_A agonists (diazepam, muscimol) prevented the development of the disease, a GABA_B agonist (baclofen) worsened clinical signs. Additionally, the GABA_A agonists added in vitro inhibited T-cell proliferation and increased glutamate release but the GABA_B agonist acted stimulating T-cell proliferation and decreasing glutamate release. In conclusion, these results indicate that the GABAergic system modulate the EAE development depending on the activated pathway.