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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD078678-01
Application #
8619205
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Grave, Gilman D
Project Start
2013-12-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$220,500
Indirect Cost
$70,500
Name
University of Alabama Birmingham
Department
Neurosciences
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Cavender, Chapin E; Gottipati, Manoj K; Parpura, Vladimir (2015) Trafficking of excitatory amino acid transporter 2-laden vesicles in cultured astrocytes: a comparison between approximate and exact determination of trajectory angles. Amino Acids 47:357-67
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Martineau, Magalie; Parpura, Vladimir; Mothet, Jean-Pierre (2014) Cell-type specific mechanisms of D-serine uptake and release in the brain. Front Synaptic Neurosci 6:12
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Gottipati, Manoj K; Verkhratsky, Alexei; Parpura, Vladimir (2014) Probing astroglia with carbon nanotubes: modulation of form and function. Philos Trans R Soc Lond B Biol Sci 369:20130598
Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir (2014) Neuroglia in ageing and disease. Cell Tissue Res 357:493-503
Gottipati, Manoj K; Bekyarova, Elena; Brenner, Michael et al. (2014) Changes in the morphology and proliferation of astrocytes induced by two modalities of chemically functionalized single-walled carbon nanotubes are differentially mediated by glial fibrillary acidic protein. Nano Lett 14:3720-7
Verkhratsky, Alexei; Parpura, Vladimir (2014) Neurological and psychiatric disorders as a neuroglial failure. Periodicum biologorum 116:115-124

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