Enteric Neurons In Parkinson'S Disease is a cell type relevant to neurodegenerative disease research. This page covers its role in brain function, involvement in disease processes, and significance for therapeutic strategies.
Enteric neurons are neurons located in the gastrointestinal tract that form the enteric nervous system (ENS), often called the "second brain." These neurons are critically involved in Parkinson's disease (PD) due to the presence of alpha-synuclein pathology in the gut years before motor symptoms appear—the brain-gut axis hypothesis of PD pathogenesis.
The ENS contains two primary neural networks:
-
Myenteric plexus (Auerbach's plexus)
- Located between longitudinal and circular muscle layers
- Controls gut motility
- Primary coordinator of peristalsis
-
Submucosal plexus (Meissner's plexus)
- Located in the submucosa
- Regulates secretion and blood flow
- Sensory functions
Enteric neurons include:
- Cholinergic neurons: Excitatory, promote motility
- Nitric oxide (NO) neurons: Inhibitory, relax smooth muscle
- VIP neurons: Secretion modulation
- 5-HT neurons: Sensory signaling
- Primary afferent neurons: Gut-brain communication
According to the Braak hypothesis:
- Pathogenic agents enter via the gut
- Alpha-synuclein pathology begins in enteric neurons
- Pathology spreads via the vagus nerve to the brainstem
- Later progresses to midbrain and cortex
- Lewy bodies found in enteric neurons pre-mortem
- Colon biopsies detect phosphorylated alpha-synuclein
- Constipation often precedes motor symptoms by years
- Vagotomy reduces PD risk
PD patients commonly experience:
- Constipation: Most common GI symptom
- Gastroparesis: Delayed gastric emptying
- Small intestinal bacterial overgrowth (SIBO)
- Dysphagia: Swallowing difficulties
- Alpha-synuclein pathology: Direct neuronal damage
- Autonomic dysfunction: Vagal nerve impairment
- Medication effects: Dopaminergic drugs affect gut motility
- Microbiome changes: Altered gut flora
PD patients show:
- Reduced microbial diversity
- Increased pro-inflammatory species
- Decreased anti-inflammatory bacteria
- Reduced short-chain fatty acid (SCFA) producers
- Inflammation: Systemic inflammation affects brain
- Metabolites: SCFAs modulate microglial activity
- Pathogen transmission: Potential for prion-like spread
- Rectal biopsy: Detection of alpha-synuclein
- Colonoscopy: Early pathology detection
- Gut microbiome: Potential diagnostic marker
- Probiotics: Modulate gut microbiome
- Antibiotics: Treat SIBO
- Laxatives: Manage constipation
- Dietary interventions: Fiber, Mediterranean diet
The study of Enteric Neurons In Parkinson'S Disease 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.
- Braak H, et al. (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiology of Aging. PMID:12446299.
- Klingelhoefer L, Reichmann H. (2015). Pathogenesis of Parkinson disease—the gut-brain axis and environmental factors. Nature Reviews Neurology. PMID:26503591.
- Sampson TR, et al. (2016). Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. PMID:27984726.
- Beach TG, et al. (2010). Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathologica. PMID:20373143.
- Cersosimo MG, Benarroch EE. (2012). Neural control of the gastrointestinal tract: implications for Parkinson disease. Journal of Parkinson's Disease. PMID:23988793.