| Lineage |
Neural Crest > Enteric Nervous System |
| Markers |
PGP9.5, HuC/D, nNOS, ChAT, VIP, CGRP |
| Brain Regions |
Enteric Nervous System - Mesenteric Plexus |
| Disease Relevance |
Hirschsprung Disease, GI Dysmotility, Parkinson's Disease |
Mesenteric Plexus Neurons is an important cell type in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Mesenteric plexus neurons are enteric neurons located within the mesenteric plexus (also known as the plexus of Auerbach) of the gastrointestinal tract. This plexus lies between the longitudinal and circular muscle layers and coordinates peristalsis and segmentation movements of the intestine[^1]. The mesenteric plexus contains a diverse population of neurons including excitatory and inhibitory motor neurons, interneurons, and secretomotor neurons.
¶ Anatomy and Location
The mesenteric plexus (Auerbach's plexus) is one of two major enteric plexuses:
- Location: Between outer longitudinal and inner circular muscle layers
- Function: Primary regulator of intestinal motility
- Connections: Communicates with submucosal plexus and central nervous system
- Parasympathetic: Vagus nerve (cranial) and pelvic nerves (sacral)
- Sympathetic: Via prevertebral ganglia (celiac, superior mesenteric, inferior mesenteric)
- Function: Stimulate smooth muscle contraction
- Neurotransmitter: Acetylcholine
- Targets: Circular and longitudinal muscle
- Function: Smooth muscle relaxation
- Neurotransmitter: Nitric oxide (NO)
- Co-transmitters: ATP, VIP
- Descending interneurons: Propagate inhibitory signals
- Ascending interneurons: Propagate excitatory signals
- Function: Regulate secretion and blood flow
- Neurotransmitters: ACh, VIP
- Source: Vagal neural crest (somites 1-7)
- Migration: Along the developing gut tube
- Colonization: Complete by week 7 of human development
Failure of neural crest cell migration leads to:
- Absent enteric neurons in distal colon
- Functional obstruction
- Megacolon[^2]
¶ Parkinson's Disease and the Gut
- Lewy bodies found in enteric neurons
- May precede brain involvement
- Braak hypothesis: Pathology spreads from gut to brain via vagus nerve[^3]
- Constipation (most common)
- Delayed gastric emptying
- Dysphagia
- Fecal incontinence
- Slow-wave potentials in smooth muscle
- Enteric neuronal networks generate rhythmic activity
- Synaptic connections between neurons
- Mechanosensitivity to gut distension
- Diabetic enteropathy
- Post-surgical dysmotility
- Irritable bowel syndrome
- Prokinetic agents (metoclopramide, domperidone)
- Nitric oxide synthase inhibitors
- 5-HT4 agonists
¶ Parkinson's Disease and the Gut-Brain Axis
The mesenteric plexus has emerged as a critical site in understanding Parkinson's disease pathogenesis:
- Early involvement: Alpha-synuclein pathology appears in enteric neurons years before motor symptoms
- Lewy pathology: Phosphorylated alpha-synuclein inclusions found in mesenteric plexus neurons[^1]
- Prion-like spread: Hypothesis that pathology spreads from gut to brain via vagus nerve
| GI Symptom |
Prevalence in PD |
Neural Correlate |
| Constipation |
50-80% |
Reduced neuronal nitric oxide |
| Gastroparesis |
30-50% |
Dysfunction of inhibitory neurons |
| Small intestinal bacterial overgrowth |
25-30% |
Motility disorders |
- Neuronal loss: Decreased nNOS-expressing neurons in advanced PD
- Alpha-synuclein deposition: Found in myenteric and submucosal plexuses
- Inflammation: Increased immune activation in enteric ganglia
Enteric neurons in PD exhibit:
- Complex I deficiency
- Increased reactive oxygen species
- Impaired mitophagy
- Energy depletion affecting pacemaking
The aggregation cascade:
- Native alpha-synuclein: Normally unfolded monomer
- Oligomerization: Formation of toxic oligomers
- Fibril formation: Lewy body constituents
- Spread: Inter-neuronal propagation
Contributing factors:
- Catecholamine oxidation
- Mitochondrial ROS
- Neuroinflammation
- Environmental toxins
The mesenteric plexus offers diagnostic opportunities:
- Rectal biopsies: Detection of early alpha-synuclein pathology
- GI motility tests: Functional assessment of enteric neurons
- Biomarker panels: Combined enteric and CNS markers
| Strategy |
Mechanism |
Current Status |
| Alpha-synuclein antibodies |
Immunotherapy |
Phase 3 trials |
| GBA enzyme enhancement |
Lysosomal function |
Phase 2 trials |
| Microbiome modulation |
Gut-brain axis |
Investigational |
| Neuroprotective agents |
Mitochondrial support |
Preclinical |
- Immunohistochemistry: Alpha-synuclein (pSer129), TH, nNOS
- Whole-mount preparations: Network analysis of plexus
- Electron microscopy: Ultrastructural changes
- Organ bath physiology: Muscle contraction studies
- Calcium imaging: Neuronal activity mapping
- Organoids: Patient-derived gut modeling
The study of Mesenteric Plexus 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.
- Braak et al., Staging of brain pathology related to sporadic Parkinson's disease (2003)
- Sharon et al., The enteric bacterial metabolites and their receptors (2019)
- Cheng et al., Alpha-synuclein in the gastrointestinal tract (2020)
- Cersosimo et al., Gastrointestinal manifestations in Parkinson's disease (2013)
- Poirier et al., Mitochondrial dysfunction in Parkinson's disease (2016)
- Furness, The Enteric Nervous System (2012)
- Heanue & Pachnis, Hirschsprung disease (2019)
- Braak et al., Parkinson's disease: staging in the brain (2003)
- Gershon, The Second Brain (1998)
- Furness et al., Neuronal coding in the enteric nervous system (2019)