The Role of JAK and STAT3 in Regulation of Secretory Function of Neuroglial Cells of Different Types in Ethanol-Induced Neurodegenerationt

• Published in: Bulletin of experimental biology and medicine 2022-04, Vol.172 (6), p.686-690
• Main Authors: Zyuz’kov, G. N., Zhdanov, V. V., Miroshnichenko, L. A., Polyakova, T. Yu, Simanina, E. V., Danilets, M. G., Minakova, M. Yu, Churin, A. A., Agafonov, V. I.
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Ethanol; Ethanol - toxicity; Glial cells; Growth factors; Internal Medicine; Janus Kinases - metabolism; Laboratory Medicine; Mice; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Microglial cells; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Neurodegeneration; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurogenesis; Neuroglia - metabolism; Neuronal-glial interactions; Neurotrophic factors; Oligodendrocytes; Pathology; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Stimulants
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-022-05457-8

The effects of JAK and STAT3 inhibitors on the production of neurotrophic growth factors by different types of neuroglial cells were studied under conditions of in vitro and in vivo models of ethanol-induced neurodegeneration. It was shown that these signaling molecules do not participate in the secretion of neurotrophins by intact astrocytes and oligodendrocytes. The inhibitory role of JAK in the regulation of this function of microglial cells was revealed. We also revealed significant changes in the role of JAK and the presence of STAT3 specifics within the framework of JAK/STAT signaling in the production of growth factors by various glial elements under the influence of ethanol. Neurodegeneration modeled in vitro led to the appearance of a “negative” effect of STAT3 on the production of neurogenesis stimulants by all types of glial cells. Moreover, the role of STAT3 in oligodendrocytes and microglial cells generally corresponded to that of JAK/STAT signaling. In astrocytes, only selective blockade of STAT3 (but not JAK) led to stimulation of their function. In mice subjected to prolonged peroral alcoholization, the neuroglial responses to the pharmacological regulation of JAK/STAT signaling were different. An inversion of the role of JAK and STAT3 in the production of neurotrophins by oligodendrocytes was noted. In addition, JAK inhibitor did not stimulate secretory function of microglial cells under conditions of prolonged exposure to ethanol in vivo .