Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins

The BTBR mouse model of idiopathic autism – Current view on mechanisms

“…myelin basic protein, MBP and myelin associated glycoprotein, MAG). They also displayed reduced levels of staining with ferric alum, indicating myelin disruption, in comparison to B6 controls (Wei et al 2016a). These results are in line with histopathological examination of BTBR brain tissue (Stephenson et al 2011), which showed reduction of myelin markers such as 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and MBP, as well as an increase in the oligodendrocyte precursor NG2.…”

“…As indicated by transcriptomic and proteomic studies, axon guidance, neurogenesis (Daimon et al 2015) as well as myelination (Wei et al 2016a) and oligodendrocyte generation (Jasien et al 2014, Wei et al 2016a) are differently regulated in BTBR brains as compared with B6 mice. The combination of the acallosal phenotype with decreased neurogenesis (Stephenson et al 2011) displayed by BTBR mice provides a unique opportunity to study the role of both of these factors in the development of normosocial behaviors.…”

Delayed myelination and neurodevelopment in male seizure‐prone versus seizure‐resistant rats

“…Of relevance, given the comorbid ASD/ADHD features manifest in the FAST strain, aberrant myelination has been proposed as a pathophysiological factor for persistent ADHD symptoms and poor cognitive performance in adult ADHD patients . Moreover, abnormal callosal myelin development in children with autism and in the Black and Tan Brachyury mouse model of ASD and behavioral impairments have been associated with myelin protein down‐regulation and abnormalities in myelin formation . These studies, and the finding that naive FAST rats live seizure‐free, suggest that the delay in myelination observed in FAST versus SLOW pups is mechanistically linked to their ADHD/ASD‐like behaviors and seizure vulnerability.…”

“…9 Moreover, abnormal callosal myelin development in children with autism 7 and in the Black and Tan Brachyury mouse model of ASD 38 and behavioral impairments have been associated with myelin protein down-regulation and abnormalities in myelin formation. 39 These studies, and the finding that naive FAST rats live seizure-free, suggest that the delay in myelination observed in FAST versus SLOW pups is mechanistically linked to their ADHD/ASD-like behaviors and seizure vulnerability. Certainly, any formative compromise to the insulating capacity of the myelin sheath is likely to negatively impact cognitive development and facilitate seizure recruitment.…”

Elevated lysine crotonylation and succinylation in the brains of BTBR mice

“…Based on the evidence from the literature and our results, we speculate that increased histone crotonylation may have effects on neuronal maturation, migration, and proliferation. At the same time, we previously have detected that a total of 126 proteins were differentially expressed between BTBR mice and B6 mice (Wei et al, 2016b). As a transcriptional activator, whether histone crotonylation was involved in the differential expression of these proteins is unclear currently and needs to be further verified.…”