Microtubule disarray in cortical dendrites and neurobehavioral failure. I. Golgi and electron microscopic studies.
Cortical biopsies obtained from 5 young children with severe neurobehavioral retardation of unknown etiology have been analyzed using Golgi and EM techniques. The normally cylindrical geometry of individual dendritic processes of pyramidal and non-pyramidal neurons is interrupted by the formation of distinct varicosities. While over 90% of observed cells are affected, the extent of varicosity formation varies from cell to cell and is most prominent in medium and small pyramidal cells. Varicosities may occur in the periphery only, or they may extend proximally to primary dendritic trunks. Accompanying changes include thin and irregular proximal processes, loss of dendritic spines, and predominance of long, thin tortuous spines. Ultrastructural analysis reveals characteristic changes in the cytoskeleton of these processes. Microtubules, within the larger proximal processes, twist and turn, relative to one another and relative to the long axis of the process. In varicose regions, microtubules course in roughly parallel array through constricted segments, only to splay away from one another on entering an expansion. Synapses are evident on constricted and expanded segments, as well as on spines. Alterations in dendritic structure of both pyramidal and non-pyramidal neurons may represent a primary target in the pathobiological process underlying neurobehavioral failure.
D002540:Cerebral Cortex / Q000473:pathology* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure*; D002658:Developmental Disabilities / Q000473:pathology*; D005260:Female; D006056:Golgi Apparatus / Q000648:ultrastructure; D006801:Humans; D007223:Infant; D008297:Male; D008854:Microscopy, Electron; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure*; D013194:Staining and Labeling