Special LMNN SEMINAR // "News from the gut: The Enteric nervous system in health and disease”

The gastrointestinal tract harbors an intrinsic nervous system, that spans from the eophagus down to the large intestine, the so called enteric nervous system (ENS). There are more neurons to befound in the ENS, than in the spinal chord. The ENS has to adapt to constant changes during development or in diseases, which leads to an enormous plasticity of the system. The ENS takes part in both gastrointestinal (Crohns disease) and systemic diseases (i.e.diabetis). Currently, there is an intense dabate concerning the role of the ENS in neurodegeneration. Here we discuss an onset of i.e. Parkinsons disease in the gut, or the option to treat neurodegeneration by changing the microbiome.
The working group ENS (AGENS) under the lead of Karl-Herbert Schäfer investigates changes wihin the ENS, due to nutritional, toxic, inflammatory or neurodegenerative impacts. So it could be demonstrated that inflammatoric molecules such as bacterial Lipopolysaccharides do have an enourmous impact on the neural stem cell population within the ENS. Since Alzheimers disease is supposed to have an inflammatory component, it is not a big surprise to see changes i.e. in TLR4 expresion in the ENS in AD models. In in vitro models of both AD and PD, an immediate impact of Amyloid-b or alpha-synuclein on cultured enteric neuronal networks and functions was shown.
Besides its role in all kind of diseases, the ENS is an ideal autologous neural stem cell source. In all parts of the enteric nervous system, nestin (a neural stem cell marker) positive cells, can be identified, isolated and grown in so called neurosphere cultures. These neurospheres can be dissociated and differentiated to neurones and glial cells. The cells can also be identified in the human gut and isolated from easily accesible tissues, such as the appendix. Human enteric neurospheres could succesfully be grown and transplanted into rodent brain slices to demonstrate the feasibility of a celular therapy. So the ENS plays not only a role as a potential source of biomarkers for the early diagnosis of neurodegenerative diseases, it might also deliver the appropriate cells for their treatment.