Precocious myelination in a mouse model of autism

Abstract

Autism spectrum disorder (ASD) has been hypothesized to be a result of altered connectivity in the brain. Recent imaging studies suggest accelerated maturation of the white matter in young children with ASD, with underlying mechanisms unknown. Myelin is an integral part of the white matter and critical for connectivity; however, its role in ASD remains largely unclear. Here, we investigated myelin development in a model of idiopathic ASD, the BTBR mice. Magnetic resonance imaging revealed that fiber tracts in the frontal brain of the BTBR mice had increased volume at postnatal day 6, but the difference reduced over time, reminiscent of the findings in young patients. We further identified that myelination in the frontal brain of both male and female neonatal BTBR mice was increased, associated with elevated levels of myelin basic protein. However, myelin pattern was unaltered in adult BTBR mice, revealing accelerated developmental trajectory of myelination. Consistently, we found that signaling of platelet-derived growth factor receptor alpha (PDGFRα) was reduced in the frontal brain of neonatal BTBR mice. However, levels of microRNA species known to regulate PDGFRα signaling and myelination were unaltered. Together, these results suggest that precocious myelination could potentially contribute to increased volume and connectivity of the white matter observed in young children with ASD.

Atypical visual processing in a mouse model of autism

“…In addition, recent studies have revealed changes in both structural and functional connectivity of the primary visual cortex in the BTBR mice 70 , 71 , providing further evidence that visual pathways and central visual processing are abnormal in this model. Finally, many investigations in the BTBR mice have revealed other differences in genetic and epigenetic regulation, neurotransmission, and structural and functional connectivity in the brain, as well as in the immune system 21 – 25 , 72 , 73 . Given that many of these differences are similar to those found in individuals with ASD 3 , 22 , 24 , they might contribute to the atypical visual processing described here.…”

Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder

“…Abnormal development in the white matter and myelination has been found in animal models of ASD [ 55 , 56 , 57 , 58 , 59 ] and humans [ 60 , 61 ]. Neuroimaging studies support the notion that ASD patients have a complex and dynamic disorder [ 62 ] in which the level of white matter involvement is associated with clinical severity [ 60 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

“… Oligodendrocyte lineage and molecular markers (genes or proteins) expressed under physiological and ASD conditions. Each human and mouse illustration indicates whether the molecular abnormality was found in clinical or experimental conditions [ 29 , 55 , 56 , 121 , 122 , 123 , 124 ]. …”

Ultrastructural and diffusion tensor imaging studies reveal axon abnormalities in Pompe disease mice

“…The lateral corpus callosum of mice was rapidly dissected and immersed in 2% paraformaldehyde and 2.5% glutaraldehyde in 0.1 M cacodylate buffer at pH 7.4 overnight at 4 °C. Samples were processed as previously reported 34 , 35 . After washing three times with the same buffer, the samples were postfixed in 1% osmium tetroxide buffered with cacodylate for 1 h at room temperature, dehydrated through a graded series of ethanol and embedded in Spurr’s resin.…”