[Instability of chromosomes in human nerve cells (normal and with neuromental diseases)]

It is assumed that the genetic mechanism of pathogenesis of such widely spread neural and mental diseases as schizophrenia (SZ), autism, ataxia-telangiectasia (AT), and Alzheimer's disease (AD) is associated with structural and functional genomi? instaility in brain cells. Aneuploidy is one of the most important biological markers of genomic instability. The currently available methods of molecular cytogenetics (I-mFISH, QFISH, and ICS-MCB) facilitate the solution of numerous fundamental biological problems, including analysis ofgenomic variations in brain cells. Using these methods, we have studied for the first time aneuploidy in human embryo and adult brain cells (normal and with AT, AD, and SZ) as well as in blood cells of children with autism. The level of aneuploidy was increased two- to threefold in the embryo brain with a subsequent reduction of the number of abnormal cells in the adult brain. In the case of SZ, mosaic aneuploidy for chromosomes 1, 18, and X was found. The study of blood cells from children with autism showed chromosomal mosaicism for chromosomes X, 9, and 15. In the case of AT, we observed a global expression of aneuploidy in up to 20-50% of cortex and cerebellum neurons. In addition, a local instability of chromosome 14 was revealed in the degenerating cerebellum in the form of breaks in the 14q12 region. In the case of AD, a tenfold increase was observed in the level ofaneuploidy for chromosome 21 in brain sections subjected to neurodegeneration. These data indicate that mosaic genomic instability in nerve cells is one of the mechanism of neurodegenerative and mental diseases.