myelin-basic-protein and Autism-Spectrum-Disorder

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.

Topics: Animals; Autism Spectrum Disorder; Brain; Disease Models, Animal; Female; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Myelin Basic Protein; Nerve Fibers, Myelinated; Receptor, Platelet-Derived Growth Factor alpha; White Matter

The biological basis of the increased risk for psychiatric disorders seen in 15q11.2 copy number deletion is unknown. Previous work has shown disturbances in white matter tracts in human carriers of the deletion. Here, in a novel rat model, we recapitulated low dosage of the candidate risk gene CYFIP1 present within the 15q11.2 interval. Using diffusion tensor imaging, we first showed extensive white matter changes in Cyfip1 mutant rats, which were most pronounced in the corpus callosum and external capsule. Transmission electron microscopy showed that these changes were associated with thinning of the myelin sheath in the corpus callosum. Myelin thinning was independent of changes in axon number or diameter but was associated with effects on mature oligodendrocytes, including aberrant intracellular distribution of myelin basic protein. Finally, we demonstrated effects on cognitive phenotypes sensitive to both disruptions in myelin and callosal circuitry.

Topics: Adaptor Proteins, Signal Transducing; Animals; Autism Spectrum Disorder; Axons; Behavior, Animal; Corpus Callosum; Diffusion Tensor Imaging; Disease Models, Animal; Gene Knockout Techniques; Haploinsufficiency; Humans; Male; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Oligodendroglia; Rats; White Matter

Brain specific-proteins are not found in other tissues and measurement non-invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain-specific protein values as brain damage markers in children with autism spectrum disorder (ASD).. 35 children with ASD and 31 healthy subjects were included in the study. Sociodemographic form and Childhood Autism Rating Scale (CARS) were applied to each subject. Serum neuron specific enolase (NSE), S100B, Myelin basic protein (MBP) and Glial fibrillary acidic protein (GFAP) values ​​were measured with ELISA.. There was no significant difference between the two groups for NSE, MBP and S100B values (p=0.242; p=0.768; p=0.672, respectively). However, GFAP values ​​in the patient group were statistically significantly higher (mean±SD: 0.463±0.392ng/ml) than in the healthy control group (mean±SD: 0.256±0.111ng/ml) (p<0.001). In addition, there was a significant positive correlation between serum GFAP values ​​and CARS score in all subjects and in the patient group (r=0.599; p<0.001 and r=0.380; p=0.024, respectively).. While serum NSE, MBP, and S100B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity.

Topics: Autism Spectrum Disorder; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Glial Fibrillary Acidic Protein; Humans; Male; Myelin Basic Protein; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit