Neurobiological substrates underlying corpus callosum hypoconnectivity and brain metabolic patterns in the valproic acid rat model of autism spectrum disorder
| Autor: | Leandro Urrutia, Nonthué Alejandra Uccelli, Martín Gabriel Codagnone, German Falasco, Nadia Levanovich, Marianela Evelyn Traetta, Analía Reinés, María Victoria Rosato Siri, Juana M. Pasquini, Silvia Vazquez |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Autism Spectrum Disorder Corpus callosum Somatosensory system Biochemistry Corpus Callosum 03 medical and health sciences Cellular and Molecular Neuroscience Myelin 0302 clinical medicine Pregnancy Internal medicine medicine Animals Rats Wistar Social Behavior Tomography Emission-Computed Single-Photon Valproic Acid biology Brain medicine.disease Oligodendrocyte Rats Astrogliosis Myelin basic protein 030104 developmental biology medicine.anatomical_structure Endocrinology Prenatal Exposure Delayed Effects Exploratory Behavior Hypermetabolism biology.protein Female lipids (amino acids peptides and proteins) Nerve Net 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neurochemistry. 159:128-144 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.15444 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text