Presinaptic dysfunctions in different brain areas of rats with experimental autoimmune encephalomyelitis (EAE)

CHANADAY RICAGNI NATALÍ L.; VILCAES A. ALEJANDRO; DEGANO ALICIA L.; ROTH GERMAN A.

Huerta Grance, Córdoba

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN).; 2012

SAN

EAE is a model that mimics many of the clinical and pathological features of multiple sclerosis (MS). While MS and EAE research has been mostly focused on spinal cord inflammation/demyelination, the extent and implications of gray matter atrophy are still not fully understood. Herein we show that Ca2+-dependent glutamate release from isolated synaptosomes is specifically impaired in frontal cortex and striatum from rats with EAE, with no changes in total intraterminal glutamate content. Synapsin I is necessary for synaptic vesicle mobilization to the active zone as well as for vesicle recycling and anchoring to the actin cytoskeleton. The former is regulated by CaMKII phosphorylation of P-sites 1 to 3 and the latter is triggered by Erk1/2 (MAPK) phosphorylation of P-sites 4 and 5. In synaptosomes from EAE rats, depolarization-induced phosphorylation on P-site 3 of Synapsin I is reduced whereas Erk1/2 autophosphorylation is increased. All these changes rapidly reverse when the animals begin to recover from the clinical signs of the disease. These data indicate that presynaptic machinery is affected in EAE, unraveling in part the mechanism of neural dysfunction. Moreover, it might contribute to clinical development as it occurs in brain areas related to motor control and learning.