Neurogenesis is a complex process which governs embryonic brain development and is importants for brain plasticity throughout the whole life. Postnatal neurogenesis occurs in neurogenic niches that regulate the processes of proliferation and differentiation of stem and progenitor cells under the action of stimuli that trigger the mechanisms of neuroplasticity. Cells of glial and endothelial origin are the key regulators of neurogenesis. It is known that physiological neurogeneses is crucial for memory formation, whereas reparative neurogenesis provides partial repair of altered brain structure and compensation of neurological deficits caused by brain injury. Dysregulation of neurogenesis is a characteristics of various neurodevelopmental and neurodegenerative diseases, particularly, Alzheimer's disease which is very important medical and social problem. In the in vitro model of the neurogenic niche using hippocampal neurospheres as a source of stem/progenitor cells and astrocytes, we studied effects of astrocyte activation on the expression of markers of different stages of cell proliferation and differentiation. We found that aberrant mechanisms of development of stem and progenitor cells, caused by the beta-amyloid (Aβ1-42), can be partially restored by targeted activation of GFAP-expressing cells in the neurogenic niche.
Neĭrogenez – slozhnyĭ protsess, kotoryĭ opredeliaet razvitie golovnogo mozga v émbrional'nom periode; on vazhen dlia protsessov neĭroplastichnosti na protiazhenii vseĭ zhizni organizma. Postnatal'nyĭ neĭrogenez proiskhodit v neĭrogennykh nishakh, kotorye obespechivaiut reguliatsiiu protsessov proliferatsii i differentsirovki stvolovykh i progenitornykh kletok pri deĭstvii stimulov, zapuskaiushchikh mekhanizmy plastichnosti golovnogo mozga. Kletki glial'noĭ i éndotelial'noĭ prirody v neĭrogennykh nishakh iavliaiutsia kliuchevymi reguliatorami mekhanizmov neĭrogeneza. Izvestno, chto v fiziologicheskikh usloviiakh neĭrogenez vazhen dlia protsessov zapominaniia, a reparativnyĭ neĭrogenez obespechivaet, kak pravilo, chastichnoe vosstanovlenie povrezhdennykh struktur mozga i kompensatsiiu nevrologicheskikh defitsitov, obuslovlennykh takim povrezhdeniem. Dizreguliatsiia neĭrogeneza kharakterna dlia mnogikh narusheniĭ razvitiia golovnogo mozga i neĭrodegenerativnykh zabolevaniĭ, v chastnosti, bolezni Al'tsgeĭmera, iavliaiushcheĭsia aktual'noĭ mediko-sotsial'noĭ problemoĭ. V modeli neĭrogennoĭ nishi in vitro s ispol'zovaniem gippokampal'nykh neĭrosfer nami pokazany éffekty aktivatsii astrotsitov na ékspressiiu markerov raznykh stadiĭ proliferatsii i differentsirovki kletok-uchastnikov neĭrogeneza. Ustanovleno, chto aberrantnye mekhanizmy razvitiia stvolovykh i progenitornykh kletok, vyzvannye deĭstviem beta-amiloidnogo peptida (Aβ1-42), mogut byt' chastichno vosstanovleny pri adresnoĭ aktivatsii GFAP-ékspressiruiushchikh kletok neĭrogennoĭ nishi.
Keywords: astrocytes; neural stem cells; neurogenesis; neurogenic niche; optogenetics.