Neurodegenerative disorders and gut-brain interactions
Alpana Singh, … , Ted M. Dawson, Subhash Kulkarni
Alpana Singh, … , Ted M. Dawson, Subhash Kulkarni
Published July 1, 2021
Citation Information: J Clin Invest. 2021;131(13):e143775. https://doi.org/10.1172/JCI143775.
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Neurodegenerative disorders and gut-brain interactions

Abstract

Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, are affected by or involved in the etiology of these debilitating and progressive disorders has been understudied. Studies in recent years have shown how CNS and gut biology, aided by the gut-brain connecting neurons, modulate each other’s functions. These studies underscore the importance of exploring the gut-innervating and gut-brain connecting neurons of the CNS and gut function in health, as well as the etiology and progression of dysfunction in NDs. In this Review, we discuss our current understanding of how the various gut-innervating neurons and gut physiology are involved in the etiology of NDs, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, to cause progressive CNS and persistent gut dysfunction.

Authors

Alpana Singh, Ted M. Dawson, Subhash Kulkarni

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Figure 3

Top-down and bottom-up progression models of PD.

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Top-down and bottom-up progression models of PD. The progression of PD i...
The progression of PD in patients is known to follow two different progression patterns. (A) The first follows Braak’s stages, where the ascent of the LP occurs from the (i) vagal or sympathetic nerves to the (ii) dorsal motor vagus nucleus in the brainstem, which then progresses to (iii) the ventral tegmental area, (iv) the mesocortex, and (v, vi) the neocortex. (B) On the other hand, the second pattern follows the top-down pathway, which originates near the (i) midbrain and (ii) ventral tegmental area, and then spreads to (iii) the mesocortical and (iv, v) neocortical regions as well as descends the (vi) medulla into the dorsal motor vagus nucleus in the brainstem, from where it progresses down (vii) the vagus nerve and descends into the spinal cord to spread down the spinal and sympathetic pathways. Illustration adapted with permission from Noelle Burgess at the Institute for Cellular Engineering of Johns Hopkins University.