title: Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome.
abstract: Many syndromes associated with mental retardation (MR) are characterized by cortical dendritic anomalies. Despite their morphological similarity, these changes appear to involve different stages of dendritic development. The neuronal cytoskeleton, which includes microfilaments, neurofilaments and microtubules, is essential for these developmental processes. Levels and phosphorylation of microtubule-associated proteins (MAPs), which stabilize microtubules, seem to determine different stages of dendritic formation with certain MAPs (e.g. MAP-2) appearing to mediate the effects of external modulators upon these processes. Early studies on neuronal cytoskeleton in MR, which have shown a selective reduction in MAP-2 expression, have focused on Rett syndrome (RS). Here, by a semiquantitative immunohistochemical analysis of the pericentral cortex, we examine the contribution of specific neuronal populations to these changes in cytoskeletal proteins. Decreased MAP-2 staining in RS was more marked in layers V-VI, while increased nonphosphorylated neurofilament immunoreactivity was found in layers II-III in RS. Age-related increases in dendritic MAP-2 immunoreactivity in layers V-VI were also absent in RS. The specificity of these cytoskeletal protein changes, their significance for RS pathogenesis and plasticity, as well as their implications for other MR-associated disorders, are also discussed.
authors.affiliation: Departments of Pathology, Neurology, Pediatrics, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and the Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA. wekaufma@jhmi.edu
authors.forename: W E
authors.initials: WE
authors.lastname: Kaufmann
authors.forename: S M
authors.initials: SM
authors.lastname: MacDonald
authors.forename: C R
authors.initials: CR
authors.lastname: Altamura
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008607:Intellectual Disability / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D015518:Rett Syndrome / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins