Enteric Neurons is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The enteric nervous system (ENS) is often called the "second brain" due to its complex neural circuitry and neurotransmitter production capabilities. Enteric neurons control gastrointestinal motility, secretion, blood flow, and immune function, and increasingly recognized as playing a crucial role in neurodegenerative diseases through the Gut-Brain Axis[1]. The ENS contains approximately 200-600 million neurons organized into two major ganglionated plexuses: the myenteric (Auerbach's) plexus and the submucosal (Meissner's) plexus[2].
Enteric neurons are highly diverse in morphology and function, classified into several subtypes:
Molecular Markers:
The ENS operates largely independently of central nervous system input, though it receives modulatory input via the vagus nerve and spinal afferents. The myenteric plexus primarily controls motility patterns, while the submucosal plexus regulates mucosal function[3].
Enteric neurons produce diverse neurotransmitters:
The Gut-Brain Axis plays a significant role in Parkinson's Disease pathogenesis:
α-Synuclein Pathology: Enteric neurons accumulate Lewy bodies early in PD progression. α-Synuclein fibrils may originate in the gut and propagate via the vagus nerve to the brainstem and substantia nigra[4].
Gastrointestinal Dysfunction: Constipation and other GI symptoms often predate motor symptoms by years, reflecting ENS involvement.
Microbiome Alterations: PD patients show altered gut microbiota that may influence α-synuclein aggregation and neuroinflammation[5].
Enteric Glia: Enteric glial cells show α-synuclein pathology and may contribute to disease spread.
Gut-Brain Signaling: ENS dysfunction may contribute to AD through:
neuroinflammation: Gut inflammation can prime peripheral immune cells and exacerbate brain neuroinflammation[6].
Metabolic Links: ENS dysfunction affects nutrient sensing and may influence type 3 diabetes (brain insulin resistance).
GI Dysmotility: ALS patients frequently experience gastrointestinal complications, including delayed gastric emptying and constipation[7].
Microbiome Changes: Altered gut microbiota in ALS patients may affect disease progression.
Nutritional Support: Enteric neuron dysfunction impacts nutrition, a critical factor in ALS care.
Autonomic Failure: MSA involves profound autonomic dysfunction, including gastrointestinal dysmotility, reflecting ENS pathology.
α-Synuclein: Enteric neurons show Lewy pathology in MSA, similar to PD.
GI Dysfunction: HD patients exhibit gastrointestinal symptoms, including swallowing difficulties and constipation.
Huntingtin Expression: Mutant huntingtin is expressed in enteric neurons, potentially causing direct toxicity.
Single-cell RNA sequencing has identified multiple enteric neuron subtypes[8]:
Neuronal Subtypes:
Glial Subtypes:
Disease-Associated Genes Expressed:
This section links to atlas resources relevant to this cell type, including Allen transcriptomic references.
The study of Enteric Neurons has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Furness JB. The Enteric Nervous System. Blackwell Publishing; 2006. ↩︎
Gershon MD. The Second Brain. HarperCollins; 1998. ↩︎
Costa M, et al. Neural circuits and mediators of gastrointestinal motility in the guinea pig. Front Neurosci. 2020;14:513700. ↩︎
Braak H, et al. Staging of brain pathology related to sporadic Parkinson's Disease. Neurobiol Aging. 2003;24(2):197-211. ↩︎
Sampson TR, et al. Gut Microbiota Regulate Motor Deficits and neuroinflammation in a Model of Parkinson's Disease. Cell. 2016;167(6):1469-1480. ↩︎
Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Alzheimers Dis. 2019;70(1):231-239. ↩︎
Toepfer M, et al. Gastrointestinal dysfunction in amyotrophic lateral sclerosis. Ther Adv Neurol Disord. 2019;12:1756286418822553. ↩︎
Drokhlyansky E, et al. The Enteric Neuron and Glial Atlas. Nature. 2020;579(7800):561-566. ↩︎