Neuronal migration, abnormality

A mutation in the reeler gene has recently been associated with autism (Keller et al., 2000). Mild abnormalities in cortical neuron migration and in reelin-containing cortical interneurons have been observed in the brains of schizophrenic subjects (Guidotti et ah, 2000). Therefore, a mutation in the reelin gene has also been implicated in schizophrenia. Changes in reelin have also been reported in the hippocampus in affective disorders (Eatemi et al., 2000). 

Beasley CL, Cotter DR, Everall IP. 2002a. Density and distribution of white matter neurons in schizophrenia, bipolar disorder and major depressive disorder No evidence for abnormalities of neuronal migration. Mol Psychiatry 7 564-570. 

Rakic P, Sidman RL (1973) Weaver mutant mouse cerebellum defective neuronal migration secondary to abnormality of Bergmann glia. Proc Natl Acad Sci USA 70 240-244. 

The types of nervous system effects described in the Minamata outbreak included mental retardation retention of primitive reflexes cerebellar symptoms dysarthria hyperkinesia hypersalivation atrophy and hypoplasia of the cerebral cortex, corpus callosum, and granule cell layer of the cerebellum dysmyelination of the pyramidal tracts and an abnormal neuronal cytoarchitecture. It has been suggested that the widespread damage involved derangement of basic developmental processes, such as neuronal migration (Choi et al. 1978 Matsumoto et al. 1965) and neuronal cell division (Sager et al. 1983). 

Choi CM, Lapham LW, Amin-Zaki L, et al. 1978. Abnormal neuronal migration, deranged cerebral cortical organization and diffuse white matter astrocytosis of human fetal brain A major effect of methylmercury poisoning in utero. J Neuropathol Exp Neurol 37 719-732. 

A neurodevelopmental model has been evoked as one possible explanation for the etiology of schizophrenia." This model proposes that schizophrenia has its origins in some as yet unknown in utero disturbance, possibly occurring during the second trimester of pregnancy. Evidence for this is provided by the abnormal neuronal migration demonstrated in most studies of schizophrenic brains. This schizophrenic lesion may result in abnormalities in cell shape, position, symmetry, and connectivity, and functionally to the development... 

Kerjan, G. Gleeson, J. G. (2007). Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly. Trends... 

Barkovich AJ (1988) Abnormal vascular drainage in anomalies of neuronal migration. AJNR Am J Neuroradiol... 

D-bifunctional protein deficiency (D-BP), the second peroxisomal -oxidation disorder, was only delineated recently [6-9]. All patients identified sofar (>40 see [10]) show severe clinical abnormalities including hypotonia, craniofacial dysmorphia, neonatal seizures, hepatomegaly, and developmental delay. Most patients with D-BP deficiency die in the first year of life. A remarkable observation is that patients with D-BP deficiency show disordered neuronal migration as in ZS. 

To test the hypothesis that MeHg causes abnormal neuronal migration, we have carried out a number of experiments using organotypic and monolayer cultures of human fetal brain cells obtained from aborted fetuses. Our studies, as well as those of others, have demonstrated that many of the developmental events that occur in normal fetal brain are repeated in cultures of fetal brain tissue. 

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