Banca de DEFESA: MARIANA DE FRANCA OLIVEIRA DA SILVA

EFFECT OF CBD-RICH OIL NANOEMULSION TREATMENT ON THE BEHAVIOR AND TESTICULAR MORPHOLOGY OF RATS

WITH VALPROIC ACID-INDUCED AUTISM.

Cannabis. Cannabinoids. Nanoemulsion. Leydig cells. Testosterone.

Autism is a heterogeneous neurodevelopmental condition that begins in childhood and is characterized by impaired communication, social, and cognitive development, in addition to stereotyped behavior and restricted interest of the individual. Cannabidiol (CBD) is a lipophilic cannabinoid, which has pharmacological effects on the central nervous system that can benefit autistic individuals since there is no standard drug treatment available that works with the nuclear changes of the disease. Nanoemulsions are delivery systems that increase the water solubility and bioavailability of lipophilic compounds such as cannabidiol. This study proposed the incorporation of a cannabidiol-rich oil into a nanoemulsion, as well as evaluate the effect of this nanoemulsion on behavioral changes and on testicular morphological changes in an animal model of valproic acid (VPA)-induced autism. For that, formulations (nanoemulsions) with CBD oil in different concentrations were developed and the macroscopic and physicochemical characteristics were evaluated. The nanoemulsions were stable after thermal stress and centrifugation, and showed a droplet size smaller than 200 nm, in addition to a polydispersity index and reduced zeta potential, characterizing their homogeneity. For the induction of autism, rats received 500 mg/kg of valproic acid (VPA) diluted in saline intraperitoneally during the prenatal period, according to the experimental model described in the literature. The behavioral assessment was performed using five behavioral tests in which anxiety, locomotor and exploratory activity, stereotypies, sociability index, and social preference index were evaluated. Animals exposed to VPA during the prenatal period showed an increase in anxiety and stereotypes, and a reduction in exploratory activity, in the sociability index and in the social preference index, behavioral changes were compatible with autism. The analysis of testicular morphometric changes was performed from the analysis of seminiferous tubule morphometry, volumetric density and volume of tubular components, percentage and volume of intertubular components, and stereological and morphometric parameters of Leydig cells. Prenatal exposure to VPA generated an increase in testicular size, diameter, volume, and length of the seminiferous tubules, lumen diameter, tubule somatic index, somatic epithelium index, as well as an increase in the volume of the nucleus and cytoplasm of Leydig cells. . On the other hand, exposure to VPA reduced the height and volumetric density of the epithelium, as well as decreased serum testosterone levels. Treatment with CBD nanoemulsions was effective in reversing both behavioral changes compatible with autism, as well as testicular morphological changes and reduction of testosterone levels generated by prenatal exposure to valproic acid.