Gut neurotoxin p-cresol induces brain-derived neurotrophic factor secretion and increases the expression of neurofilament subunits in PC-12 cells.

Autor: Tevzadze G; 4-D Research Institute, Ilia State University, 3/5 Cholokashvili av, Tbilisi, 0162, Georgia., Barbakadze T; School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili ave, Tbilisi, 0162, Georgia.; I. Beritashvili Center of Experimental Biomedicine 14, Gotua Str., Tbilisi 0160, Georgia., Kvergelidze E; School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili ave, Tbilisi, 0162, Georgia., Zhuravliova E; School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili ave, Tbilisi, 0162, Georgia.; I. Beritashvili Center of Experimental Biomedicine 14, Gotua Str., Tbilisi 0160, Georgia., Shanshiashvili L; School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili ave, Tbilisi, 0162, Georgia.; I. Beritashvili Center of Experimental Biomedicine 14, Gotua Str., Tbilisi 0160, Georgia., Mikeladze D; School of Natural Sciences and Medicine, Institute of Chemical Biology, Ilia State University, 3/5 Cholokashvili ave, Tbilisi, 0162, Georgia.; I. Beritashvili Center of Experimental Biomedicine 14, Gotua Str., Tbilisi 0160, Georgia.
Jazyk: angličtina
Zdroj: AIMS neuroscience [AIMS Neurosci] 2021 Dec 23; Vol. 9 (1), pp. 12-23. Date of Electronic Publication: 2021 Dec 23 (Print Publication: 2022).
DOI: 10.3934/Neuroscience.2022002
Abstrakt: Increased p-cresol levels reportedly alter brain dopamine metabolism and exacerbate neurological disorders in experimental animals. In contrast to toxic concentrations, low doses of p-cresol may have distinct effects on neuronal metabolism. However, the role of p-cresol in synapse remodeling, neurite outgrowth, and other anabolic processes in neurons remains elusive. We propose that low doses of p-cresol affect neuronal cell structural remodeling compared with the high concentration-mediated harmful effects. Thus, the effects of p-cresol on the secretion of brain-derived neurotrophic factor (BDNF) and neurofilament subunit expression were examined using rat pheochromocytoma cells (PC-12 cells). We observed that low doses of p-cresol potentiated nerve growth factor-induced differentiation via secretion of BDNF in cultured PC-12 cells. Opioidergic compounds modulated these p-cresol effects, which were reversed by oxytocin. We propose that this effect of p-cresol has an adaptive and compensatory character and can be attributed to the induction of oxidative stress. Accordingly, we hypothesize that low doses of p-cresol induce mild oxidative stress, stimulating BDNF release by activating redox-sensitive genes. Given that the intestinal microbiome is the primary source of endogenous p-cresol, the balance between gut microbiome strains (especially Clostridium species) and opioidergic compounds may directly influence neuroplasticity.
Competing Interests: Conflict of interests: The authors declare that there are no conflicts of interest.
(© 2022 the Author(s), licensee AIMS Press.)
Databáze: MEDLINE
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