Accepted_test

The DISC1 gene plays a key role in the nervous system (NS) functioning. The DISC1 protein regulates proliferation and differentiation of neuronal stem cells, neurons migration and maturation, synapses formation and maintenance, transport of substances and cellular components, also involved in signaling cascades within cells. Less studied DISC1 functions in gliagenesis, anyway it is known DISC1 stimulate astrogenesis and determine time and place of the oligodendrocyte progenitors differentiation. With such variety of functions, mutations in the Disc1 gene are a key predictor of pathological conditions associated with neurodevelopmental disorders, disruption of synaptic transmission, intracellular signaling and circadian rhythms, for example, in psychiatric, neurodegenerative and demyelinating diseases. Disc1-knockout in mice leads to accelerated degradation of BMAL1 circadian protein through the increased activity of glycogen synthase kinase-3(GSK-3) which is an DISC1 interacting protei. Besides circadian rhythms, BMAL1 play a key role in the NS development and functioning. In the adult mice brain was shown high Bmal1expression in neurons and glial cells. Especially BMAL1 play an important role in the myelinisation and it is determined that disrupted rhythm of Bmal1expression in hippocampal CA1 and prefrontal cortex oligodendrocyte progenitor cells leads to depressive like and anxious behavior. Interesting that mice with Q31L point mutation in Disc1 gene characterized with decreased DISC1-GSK-3 interaction and increased enzymatic activity of GSK-. Study of BMAL1 abundance in the key brain structures involved in Q31L mice behavior may provide new mechanisms of mood disorders pathogenesis.