The enteric nervous system (ENS) resides in the gut wall and controls physiology of the alimentary tract. The majority of the ENS is composed of enteric glial cells (EGCs), which have been linked to a wide range of gut pathologies, e.g., inflammatory bowel disease, necrotizing enterocolitis and """"""""idiopathic"""""""" constipation. Our preliminary data point to a novel hypothesis that EGCs support normal gut function through their cell-cell connectivity established via connexin 43;the down regulation of Cx43 leads to inflammatory morphological changes and reduced motility of the gut. To test this hypothesis we will use an innovative molecular genetics approach integrated with histology, fiber-optic colonoscopy, GI transit tests in vivo, and an ex vivo imaging method of an isolated colon. This proposed investigation will gather valuable information on the novel role of Cx43 in the function of the gut and ENS. These findings will be of general interest to neurobiology. Additionally, the findings will be relevant to translational medicine, since they could open the door for the development of a cause-directed treatment for constipation and various inflammatory bowel diseases. These potential new opportunities for intervention could greatly improve clinical practice in gastroenterology by increasing the survival rate of neonatal patients suffering from necrotizing enterocolitis and substantially improve the quality of life and survival in the other ENS/EGC related gut pathologies.
This proposed investigation will gather valuable information on the novel role of connexin 43 in the function of the gut and these findings will be of general interest to neurobiology. They will also be relevant to translational medicine, since they could open the door to development of cause-directed treatment for constipation and various inflammatory bowel diseases. These new potential treatments could greatly improve clinical practice in gastroenterology by increasing the survival rate of neonatal patients suffering from necrotizing enterocolitis and substantially improving the quality of life and survival in the other gut pathologies.
| Grubiši?, Vladimir; Verkhratsky, Alexei; Zorec, Robert et al. (2018) Enteric glia regulate gut motility in health and disease. Brain Res Bull 136:109-117 |
| Zorec, R; Parpura, V; Verkhratsky, A (2018) Astroglial vesicular network: evolutionary trends, physiology and pathophysiology. Acta Physiol (Oxf) 222: |
| Stenovec, M; Trkov Bobnar, S; Smoli?, T et al. (2018) Presenilin PS1?E9 disrupts mobility of secretory organelles in rat astrocytes. Acta Physiol (Oxf) 223:e13046 |
| Grubiši?, Vladimir; Parpura, Vladimir (2017) Two modes of enteric gliotransmission differentially affect gut physiology. Glia 65:699-711 |
| Verkhratsky, Alexei; Zorec, Robert; Parpura, Vladimir (2017) Stratification of astrocytes in healthy and diseased brain. Brain Pathol 27:629-644 |
| Verkhratsky, Alexei; Rodríguez-Arellano, J J; Parpura, Vladimir et al. (2017) Astroglial calcium signalling in Alzheimer's disease. Biochem Biophys Res Commun 483:1005-1012 |
| Tewari, Shivendra G; Gottipati, Manoj K; Parpura, Vladimir (2016) Mathematical Modeling in Neuroscience: Neuronal Activity and Its Modulation by Astrocytes. Front Integr Neurosci 10:3 |
| Lim, Dmitry; Rodríguez-Arellano, J J; Parpura, Vladimir et al. (2016) Calcium signalling toolkits in astrocytes and spatio-temporal progression of Alzheimer's disease. Curr Alzheimer Res 13:359-69 |
| Wang, Yu-Feng; Parpura, Vladimir (2016) Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation. Front Cell Neurosci 10:129 |
| Pekny, Milos; Pekna, Marcela; Messing, Albee et al. (2016) Astrocytes: a central element in neurological diseases. Acta Neuropathol 131:323-45 |
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