Researchers begin to map direct gut-to-brain connection.


Researchers at Duke University have mapped a direct cell-to-cell connection between the gut and the nervous system.  The new system may change researchers’ understanding of how the brain senses that the person is ‘full’, and how that sensation might be affected by gastric bypass surgery. The opensource study, which is published in the Journal of Clinical Investigation, also shed light on a potential new mechanism giving foodborne viruses access to the brain.

The study supports the idea that there could be a real biology of gut feelings.  As soon as food contacts the wall of the gut, the brain knows in real time what’s going on in the gut.

Several years ago the team developed methods to visualize a type of cell found scattered throughout the lining of the mouse gut that is remarkably similar to a neuron. Although the cells have a normal shape on the gut’s surface, their underside bears a long arm.  The question was, why would a cell that is supposed to just release hormones have a whole arm? The team theorised that there had to be a target on the other side.

Dubbed ‘neuropods,’ these special arms are nurtured by support cells known as glia that work with neurons, which suggested at the time that they could be involved in a neuronal circuit.

In the current study, researchers traced the contacts of the neuropods in greater detail, finding that they came close to individual nerve fibers, but not blood vessels, in the small and large intestine. They found that about 60% of neuropods contacted sensory neurons, supporting the notion that they could be involved in gut sensation.

The group went a step further, showing that neuropods and neurons not only contact one another, but they connect. In a dish, single sensory neurons isolated from the brain reached out to contact a neuropod that was, on a cellular scale, about half a football field away.

For the researchers that was a point of no return.  It said that these cells know how to get closer to neurons, though how exactly is unclear. The connection was especially surprising because no one had ever cultured these cells in complete isolation from their neighbours.

Neuropods are so much like neurons, they contain much of the same machinery for sending and receiving signals, that the researchers then tried infecting the colons of mice with a disabled version of the rabies virus, which moves through the body initially by infecting neurons. The virus is routinely used as a laboratory tool for visualizing a single connection from one neuron to another.  It was a leap of faith but it worked. A week after introducing the virus, only cells with neuropods became infected.

The team explain that this provides a pathway where rabies can go from the lumen of the gut to the nervous system.  It implies that a patient might be able to get rabies by eating rabies.  The researchers state that this is a pathway that other viruses could infect the nervous system.

The new study focused on connections between neuropods and neurons closest to the intestine, the team is now working to trace the whole path from the gut to brain.

Source:  Duke University Medical Center

 

Enteroendocrine cells connect to sensory neurons in vivo and in vitro.  Coculture scheme of enteroendocrine cell and primary sensory neurons. EEC, enteroendocrine cell; TG, trigeminal neuron.  Time-lapse sequence showing how a single Cck-GFP enteroendocrine cell (green) connects to a sensory neuron (DiI-labeled, red) in vitro. The enteroendocrine cell–neuron connection is stable at 23 minutes, 14 seconds, and cells remained connected for 88 hours until the end of the experiment.  Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.  Liddle et al 2015.

Enteroendocrine cells connect to sensory neurons in vivo and in vitro. Coculture scheme of enteroendocrine cell and primary sensory neurons. EEC, enteroendocrine cell; TG, trigeminal neuron. Time-lapse sequence showing how a single Cck-GFP enteroendocrine cell (green) connects to a sensory neuron (DiI-labeled, red) in vitro. The enteroendocrine cell–neuron connection is stable at 23 minutes, 14 seconds, and cells remained connected for 88 hours until the end of the experiment. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. Liddle et al 2015.

 

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