Brian Gulbransen, Ph.D.
You might be surprised to learn that your gut has it’s own brain and that you have more neurons in your intestines than in your spinal cord. Within your intestines lies a “second brain” called the enteric nervous system. The enteric nervous system is an exceedingly complex network of neural circuits that programs a diverse array gut patterns and is responsible for controlling most gastrointestinal functions.
These normal gastrointestinal functions typically go on unnoticed but when enteric nervous system function is compromised, the results are devastating and debilitating to affected individuals. This is especially pertinent in the elderly population and gastrointestinal disorders are among the most common reason elderly individuals require assisted living. Extensive neuron death and synaptic dysfunction are observed in the aged enteric nervous system but the underlying causes of these changes are unknown.
To fully understand enteric nervous system function and the changes that occur in advanced age, we must remember that the enteric nervous system is not only made up of neurons. Within enteric ganglia a unique type of peripheral glia called enteric glia surrounds neurons, similar to the relationship between astrocytes and neurons in the central nervous system. Increasing evidence supports the notion that enteric glial cells are responsible for modulating the function of the enteric nervous system but exactly how enteric glial cells influence the function and survival of enteric neurons are unknown. The goal of our lab is to understand how enteric glial cells influence the function of the enteric neural network and how disruptions in glial function contribute to the common gut motility disorders encountered in the elderly.
Specific research interests include:
1. How do enteric glia modulate synaptic transmission in the enteric nervous system?
2. Are normal glial regulatory mechanisms lost in advanced age?
3. How do glial changes contribute to age-related enteric neurodegeneration?
We utilize several forms of advanced fluorescent microscopy in the lab to investigate these questions including:
- Calcium imaging of glial and neural activity
- Voltage-sensitive dye imaging of neural network activity
- Optogenetic stimulation of specific cell types within the enteric nervous system
- Fluorescent immunohistochemistry
Bubenheimer RK, Brown IAM, Fried DE, McClain JL and Gulbransen BD (2016) Sirtuin 3 regulates oxidative stress in enteric neurons but its function is not required for protection from inflammatory damage. Frontiers in Cellular Neuroscience, in press.
Grubiši? V and Gulbransen BD (2016) Enteric glia: The most alimentary of all glia. Journal of Physiology, in press.
Brown, IAM, Mcclain, JL, Watson, RE, Patel, BA, & Gulbransen, BD (2016) Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric Oxide. Cellular and Molecular Gastroenterology and Hepatology, 2(1): 77–91. http://doi.org/10.1016/j.jcmgh.2015.08.007
Fried DE and Gulbransen BD (2015) In situ Ca2+ imaging of the enteric nervous system. Journal of Visualized Experiments, Jan 29(95): e52506. doi:10.3791/52506 PMID: 25741967 http://www.jove.com/video/52506/in-situ-ca2-imaging-of-the-enteric-nervous-system.
Gombash SE, Cowley CJ, Fitzgerald JA, Iyer CC, Fried DE, McGovern VL, Williams KC, Burghes AHM, Christofi FL, Gulbransen BD, Foust KD (2015) SMN Deficiency Disrupts Gastrointestinal and Enteric Nervous System Function in Mice. Human Molecular Genetics, Apr 9. pii: ddv127. [Epub ahead of print] PMID: 25859009
McClain JL, Fried DE and Gulbransen BD (2015) Agonist-evoked Ca2+ signaling in enteric glia drives neural programs that regulate intestinal motility in mice. Cellular and Molecular Gastroenterology and Hepatology, 1(6):631-645. http://dx.doi.org/10.1016/j.jcmgh.2015.08.004
McClain J*, Grubiši? V*, Fried D, Gomez-Suarez RA, Leinninger GM, Sévigny J, Parpura V, Gulbransen BD (2014) Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice. Gastroenterology, 146: 497-507.
Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, Muruve DA, McKay DM, Beck PL, Mawe GM, Thompson RJ, Sharkey KA (2012) Activation of neuronal P2X7 receptor-Pannexin-1 mediates death of enteric neurons during colitis. Nature Medicine, 18: 600-604. doi:10.1038/nm.2679.
(highlighted by Faculty of 1000 and featured on Nature Medicine’s podcast, CBC TV News Calgary, CBC radio, QR77 Newsroom, Calgary Sun, Calgary Herald, 660 News, Ottawa Citizen, Vancouver Sun, The Province, Nanaimo Daily News, Victoria Times Colonist, StarPhoenix, Regina Leader-Post, Canada.com, Edmonton Journal, Windsor Star, and the Montreal Gazette).
Smyth D, McKay CM, Gulbransen BD, Phan VC, Wang A and McKay DM (2012) Interferon-gamma signals via an ERK1/2-ARF6 pathway to promote bacterial internalization by gut epithelia. Cellular Microbiology, 14 (8):1257-70. doi: 10.1111/j.1462-5822.2012.01796.x.
Lavoie EG*, Gulbransen BD*, Martín-Satué M, Sharkey KA, Sévigny J (2011) Ectonucleotidases in the digestive system: Special focus on NTPDase3 localization. American Journal of Physiology – Gastrointestinal and Liver Physiology, 300(4):G608-20. (*, co-first authors).
Gulbransen BD, Bains JS, Sharkey KA (2010) Enteric glia are targets of the sympathetic innervation of the myenteric plexus in the guinea pig distal colon. Journal of Neuroscience, 30: 6801-6809. (cover illustration and highlighted by Faculty of 1000).
Tizzano M, Gulbransen BD*, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill MEA, Silver WL, Kinnamon SC, Finger TE (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci USA, 107:3210-5. (featured in the Denver Post) (* = co-first authors).
Gulbransen BD and Sharkey KA (2009) Purinergic neuron-to-glia signaling in the enteric nervous system. Gastroenterology, 136: 1349-58 (cover illustration).
Gulbransen BD, Clapp TR, Finger TE, Kinnamon SC (2008) Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro. Journal of Neurophysiology, 99: 2929-37.
Gulbransen B, Silver W, Finger TE (2008) Solitary chemoreceptor cell survival is independent of intact trigeminal innervation. Journal of Comparative Neurology, 508: 62-71.
Gulbransen BD and Finger TE (2005) Solitary chemoreceptor cell proliferation in adult nasal epithelium. Journal of Neurocytology, 34: 117-122.
Gulbransen BD and Sharkey KA (2012) Novel functional roles for enteric glia in the gastrointestinal tract. Nature Reviews Gastoenterology & Hepatology. doi: 10.1038 [Epub ahead of print].
Gulbransen BD (2014) Enteric Glia. Colloquium Series on Neuroglia in Biology and Medicine: From Physiology to Disease. Vol. 1, No. 2, pages 1-70. A. Verkhratsky, V. Parpura (eds.). Morgan & Claypool. doi: 10.4199/C00113ED1V01Y201407NGL002. Published Aug. 11, 2014. Link on Amazon: http://amzn.com/1615046607.
Gulbransen BD (2014) Glial Cells and Interstitial Cells of Cajal. Reference Module in Biomedical Sciences. Elsevier. Michael Caplan (ed.).
Brown I and Gulbransen BD (2014) “Enteric glial cells: Implications in gut pathology”, in Pathological potential of neuroglia. Ch. 21, pages 493-518. V. Parpura, A. Verkhratsky (eds.), doi: 10.1007/978-1-4939-0974_21. Springer Science+Business Media New York.