MODULATORY EFFECT OF DIAZEPAM ON CHRONIC EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS: NEUROINFLAMATION AND BEHAVIORAL STUDIES

FABIO MC; ZALOSNIK, MI; FELIPPA AMBORT, CN; DEGANO AL

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Experimental autoimmune encephalomyelitis (EAE) is an inflammatorydemyelinating disease that mimics many of the pathologicalfeatures of multiple sclerosis (MS). The aim of the present studywas to analyze the effects of Diazepam (Dz) on EAE clinical signs,neuropathology and behavior in a chronic model of the disease.9-weeks old mice were immunized with MOG35-55 peptide (EAEgroup) or adjuvant alone (CFA group) and pertussis toxin. Beginningthe day of the clinical onset (9-12 dpi), CFA-Dz and EAE-Dzgroups were injected i.p. with Dz (2 or 4 mg/kg) every 48 hs. Afterthe acute period (26-30dpi), mice were exposed to a battery of behavioraltests in order to assess motor skills, anxiety, and cognitivedeficits. Neuropathology and inflammatory markers (Iba-1, GFAP,TNFα) were analyzed in spinal cord and hippocampus by IHC andreal-Time RT-PCR. Experimental designs were factorial 2 [Condition(EAE vs CFA)] x 2 [Treatment (Saline vs Dz)]. All data was analyzedusing two-way ANOVA, followed by Tukey test, when appropriate.We found that 2 mg/kg Dz significantly ameliorated clinical signsof the disease (p<0,05; EAE-Dz vs EAE) and cellular infiltration inspinal cord (*p<0,05; EAE-Dz vs EAE). Chronic administration of Dzdid not affect locomotor activity and anxiety behavior in any group.Cognitive deficits persisted in both EAE and EAE-Dz mice in chronicstages, while EAE-Dz mice showed a significant reduction of gliosisand inflammatory markers in the hippocampus (Iba-1, GFAP, TNF;p<0,05; EAE-Dz vs EAE). Interestingly, the expression of the benzodiazepineperipheral receptor TSPO, was lower in hippocampusfrom both Dz-treated groups (p<0.01; CFA/EAE vs CFA-Dz/EAEDz),suggesting TSPO might play a role in the effects induced byDz. Our present results show that, at the dose and schedule usedhere, Dz modulates clinical EAE without generating side effects inanimal behavior. These results may have important implications fornew therapeutic applications in MS.