myelin-basic-protein and Down-Syndrome

Trisomy 21, or Down syndrome (DS), is the most common genetic cause of developmental delay and intellectual disability. To gain insight into the underlying molecular and cellular pathogenesis, we conducted a multi-region transcriptome analysis of DS and euploid control brains spanning from mid-fetal development to adulthood. We found genome-wide alterations in the expression of a large number of genes, many of which exhibited temporal and spatial specificity and were associated with distinct biological processes. In particular, we uncovered co-dysregulation of genes associated with oligodendrocyte differentiation and myelination that were validated via cross-species comparison to Ts65Dn trisomy mice. Furthermore, we show that hypomyelination present in Ts65Dn mice is in part due to cell-autonomous effects of trisomy on oligodendrocyte differentiation and results in slower neocortical action potential transmission. Together, these results identify defects in white matter development and function in DS, and they provide a transcriptional framework for further investigating DS neuropathogenesis.

Topics: Action Potentials; Adolescent; Adult; Animals; Brain; Cell Differentiation; Child; Child, Preschool; Chromosomes, Human, Pair 17; Disease Models, Animal; Down Syndrome; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Infant; Infant, Newborn; Male; Mice; Mice, Transgenic; Mosaicism; Myelin Basic Protein; Myelin Sheath; Neural Conduction; Oligodendroglia; Postmortem Changes; Trisomy; White Matter; Young Adult

Based on a possible pathological relationship of autoimmunity to autism, antibodies reactive with myelin basic protein (anti-MBP) were investigated in the sera of autistic children. Using a screening serum dilution of 1:400 in the protein-immunoblotting technique, approximately 58% (19 of 33) sera of autistic children (< or = 10 years of age) were found to be positive for anti-MBP. This result in autistics was significantly (p < or = .0001) different from the controls (8 of 88 or only 9% positive), which included age-matched children with normal health, idiopathic mental retardation (MR) and Down syndrome (DS), and normal adults of 20 to 40 years of age. Since autism is a syndrome of unknown etiology, it is possible that anti-MBP antibodies are associated with the development of autistic behavior.

Topics: Adult; Age Factors; Antibody Specificity; Autistic Disorder; Autoantibodies; Autoimmune Diseases; Child; Child, Preschool; Double-Blind Method; Down Syndrome; Female; Humans; Infant; Intellectual Disability; Male; Myelin Basic Protein; Nerve Tissue Proteins