O estresse oxidativo e o desenvolvimento do córtex auditivo em ratos modelo de autismo: efeito do extrato antioxidante de Libidibia ferrea na formação das redes perineuronais

Abstract

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized mainly by deficiencies in social communication, repetitive behaviors and altered sensory perception. People with autism often present changes in auditory accuracy, or hyper/hyposensitivity to sound. It is known that the topographic maps and acuity of sensory systems in the brain are refined during the critical period, early postnatal life, through the maturation of parvalbumin-positive inhibitory neurons and the surrounding perineuronal network. Changes in the critical period mediated, for example, by increased oxidative stress, can have a major impact on the development of sensory perception, delaying the development of perineuronal networks in sensory cortices. Objective: The present work aims to investigate whether the administration of antioxidant molecules during the critical period of development of the primary auditory cortex can influence the development of perineuronal networks around neurons of the primary auditory cortex (Au1), secondary dorsal (AuD) and ventral secondary (AuV) model of autism rodents. Methodology: For the research, we used a rodent model of autism treated with valproic acid on embryonic day 12 (VPA rats) to induce characteristics of autism in the animals. In the critical period of Au1 development, postnatal days 10 to 12 (P10 to P12), we injected, intraperitoneally, exosomes from M2 type macrophages to transport the fruit extract of the Libidibia ferrea plant with antioxidant molecules to the brain tissue - group of rats treated with antioxidants (VPA cOxi). During the same period, we also injected exosomes without the antioxidant extract into the VPA sOxi group. The Control group did not receive injections of valproic acid or exosomes. To analyze the development of perineuronal networks in AuD, Au1 and AuV, we performed histochemistry for Wisteria floribunda, and quantified the number and density of cells marked with perineuronal network in layer IV and throughout the AuD, Au1 and AuV cortex of the experimental groups Control, VPA sOxi and VPA cOxi. Results: As a result, we observed that the number and density of cells involved by the perineuronal network in Au1 and AuV was greater in the Control group than in the VPA sOxi and VPA cOxi groups, both when quantifying all cortical layers or layer IV. There was no difference in the number and density of cells in the group treated with the antioxidant, VPA cOxi, and the untreated group, VPA sOxi. Conclusion: In the present work, it was possible to conclude that the autism model rats showed impairment in the formation of the perineuronal network around the auditory cortex neurons, indicating a deficit in the critical period of the development of the tonotopic map. The administration of fruit extract with antioxidant action in the period and/or dosage used in our study was not able to prevent the development of changes in the perineuronal network around neurons in the auditory cortices of autism model rats.