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.