PERSONAL DE APOYO
ROSATO SIRI Maria Victoria
artículos
Título:
Neurobiological substrates underlying corpus callosum hypoconnectivity and brain metabolic patterns in the valproic acid rat model of autism spectrum disorder
Autor/es:
UCCELLI, NONTHUÉ ALEJANDRA; CODAGNONE, MARTÍN GABRIEL; TRAETTA, MARIANELA EVELYN; LEVANOVICH, NADIA; ROSATO SIRI, MARÍA VICTORIA; URRUTIA, LEANDRO; FALASCO, GERMÁN; VÁZQUEZ, SILVIA; PASQUINI, JUANA MARÍA; REINÉS, ANALÍA GABRIELA
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2021 vol. 00 p. 1 - 17
ISSN:
0022-3042
Resumen:
Atypical connectivity between brain regions and altered structure of the corpus callosum (CC) in imaging studies supports the long-distance hypoconnectivity hypothesis proposed for autism spectrum disorder (ASD). The aim of this study was to unveil the CC ultrastructural and cellular changes employing the valproic acid (VPA) rat model of ASD. Male Wistar rats were exposed to VPA (450 mg/kg i.p.) or saline (control) during gestation (embryonic day 10.5), and maturation, exploration, and social behavior were subsequently tested. Myelin content, ultrastructure, and oligodendroglial lineage were studied in the CC at post-natal days 15 (infant) and 36 (juvenile). As a functional outcome, brain metabolic activity was determined by positron emission tomography. Concomitantly with behavioral deficits in juvenile VPA rats, the CC showed reduced myelin basic protein, conserved total number of axons, reduced percentage of myelinated axons, and aberrant and less compact arrangements of myelin sheath ultrastructure. Mature oligodendrocytes decreased and oligodendrocyte precursors increased in the absence of astrogliosis or microgliosis. In medial prefrontal and somatosensory cortices of juvenile VPA rats, myelin ultrastructure and oligodendroglial lineage were preserved. VPA animals exhibited global brain hypometabolism and local hypermetabolism in brain regions relevant for ASD. In turn, the CC of infant VPA rats showed reduced myelin content but preserved oligodendroglial lineage. Our findings indicate that CC hypomyelination is established during infancy and prior to oligodendroglial pattern alterations, which suggests that axon?oligodendroglia communication could be compromised in VPA animals. Thus, CC hypomyelination may underlie white matter alterations and contribute to atypical patterns of connectivity and metabolism found in ASD.