Retinal alterations in a pre-clinical model of an autism spectrum disorder

Autor(es)

Guimaraes-Souza, Elisa Maria ^[1] ; Joselevitch, Christina ^[2] ; Britto, Luiz Roberto G. ^[1] ; Chiavegatto, Silvana ^{[3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Ave Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Psychol, Dept Expt Psychol, Ave Prof Mello Moraes 1721, BR-05508030 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Ave Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sch Med, Clin Hosp HCFMUSP, Dept & Inst Psychiat, Rua Dr Ovidio Pires de Campos 785, BR-05403903 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR AUTISM; v. 10, APR 15 2019.
• Citações Web of Science: 0

Resumo

Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (WA), a useful tool to study ASD endophenotypes. Methods: Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29-35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs). Results: Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of WA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal. Conclusions: This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms. (AU)

• Processo FAPESP: 10/16469-0 - Visão e comunicação celular na retina: o papel das células bipolares de entrada mista
• Beneficiário: Christina Joselevitch
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/06100-8 - Suscetibilidade e resiliência aos efeitos do estresse psicossocial crônico na adolescência: estudo da participação da enzima neuronal de síntese do óxido nítrico (nNOS)
• Beneficiário: Silvana Chiavegatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular