Sympathetic 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.
Sympathetic neurons are components of the autonomic nervous system that regulate involuntary functions including heart rate, blood pressure, pupil dilation, sweat production, and digestive motility. Postganglionic sympathetic neurons degenerate in autonomic neuropathies, and sympathetic dysfunction is an early feature of Parkinson's disease and multiple system atrophy.
| Property |
Value |
| Cell Type Name |
Sympathetic Neurons |
| Allen Atlas ID |
Sympathetic ganglia (superior cervical, stellate, thoracic chain) |
| Lineage |
Neural crest > Sympathoblast > Sympathetic neuron |
| Marker Genes |
PHOX2B, ASCL1, TH, DBH, PHOX2A, GATA2, HAND2 |
| Brain Regions |
Sympathetic chain ganglia, prevertebral ganglia |
¶ Morphology and Markers
The sympathetic nervous system has two neurons in series:
- Location: Spinal cord (T1-L2, intermediolateral cell column)
- Axon: Thinly myelinated (B fibers), preganglionic
- Neurotransmitter: Acetylcholine (ACh)
- Receptors: Nicotinic ACh receptors on postganglionic neurons
Long, unmyelinated C fibers:
- Cell bodies: In autonomic ganglia (chain or prevertebral)
- Axon length: Can be very long (e.g., to extremities)
- Neurotransmitter: Norepinephrine (most), ACh (sweat glands)
- Receptors: Adrenergic (α1, α2, β1-3), muscarinic (M3)
- PHOX2B: Master transcription factor for sympathetic neurons
- ASCL1 (MASH1): Neural crest specification
- TH (Tyrosine hydroxylase): Rate-limiting catecholamine synthesis
- DBH (Dopamine β-hydroxylase): Norepinephrine synthesis
- PNMT (Phenylethanolamine N-methyltransferase): Epinephrine synthesis
- Phox2a, GATA2, HAND2: Transcription factors
- SLC18A2 (VMAT2): Vesicular monoamine transport
- SLC6A2 (NET): Norepinephrine transporter
-
Heart
- ↑ Heart rate (β1 receptors)
- ↑ Myocardial contractility
- ↑ Conduction velocity (AV node)
-
Blood vessels
- Vasoconstriction (α1 receptors)
- Blood pressure maintenance
- Skeletal muscle vasodilation (β2)
- Mydriasis: Radial muscle contraction (α1)
- Parasympathetic: Pupillary constriction (muscarinic)
- Clinical: Horner's syndrome (ptosis, miosis, anhidrosis)
- Eccrine sweat glands: ACh-mediated secretion (sympathetic)
- Vasoconstriction: Reduce heat loss
- Thermogenic responses: Brown adipose tissue (β3)
| Organ |
Sympathetic Effect |
Receptor |
| Heart |
↑ Rate, ↑ contractility |
β1 |
| Lungs |
Bronchodilation |
β2 |
| GI tract |
↓ Motility, ↓ secretion |
α2 |
| Kidneys |
↓ Urine output |
α1 |
| Bladder |
Urinary retention |
α1, β3 |
| Liver |
Glycogenolysis, gluconeogenesis |
β2, α1 |
The sympathetic nervous system mediates the fight-or-flight response:
- Elevated heart rate and blood pressure
- Pupillary dilation
- Bronchodilation
- Mobilization of energy stores
- Decreased non-essential functions
- Diabetic autonomic neuropathy: Most common cause of autonomic dysfunction[1]
- Cardiovascular dysfunction: Orthostatic hypotension, resting tachycardia
- GI dysfunction: Gastroparesis, constipation
- Sudomotor dysfunction: Anhidrosis, hyperhidrosis
Sympathetic dysfunction occurs in 50-80% of PD patients:
- Cardiac sympathetic denervation: Loss of cardiac norepinephrine[2]
- Orthostatic hypotension: Early prodromal feature
- Lewy pathology: Sympathetic ganglia affected
- Diagnostic biomarker: 123I-MIBG scintigraphy detects denervation
- Severe autonomic failure: More pronounced than in PD
- Sympathetic denervation: Cardiovascular dysfunction
- Peripheral neuropathy: May contribute
- Differentiates from PD: Lack of cardiac sympathetic preservation
- Pure autonomic failure: Autoimmune/drug-induced
- Autoimmune autonomic ganglionopathy: Anti-ganglionic ACh receptor antibodies
- Chagas disease: Destroy enteric and cardiac sympathetic neurons
- Guillain-Barre syndrome: Autonomic involvement
- Spinal cord injury: Loss of preganglionic neurons
Single-cell RNA sequencing of sympathetic neurons:
- PHOX2B: Master regulator
- TH, DBH: Catecholamine synthesis
- SLC6A2 (NET): Norepinephrine transporter
- SLC18A2 (VMAT2): Vesicular monoamine transporter
- ADRA1A/D, ADRB1/2/3: Adrenergic receptors
- CNTNAP2: Neuronal adhesion
- NRXN1: Neurexin family
- SNCA: Alpha-synuclein in sympathetic ganglia (PD)
- GBA1: Glucocerebrosidase (PD risk)
- LRRK2: Leucine-rich repeat kinase (PD risk)
- PANK2: Coenzyme A synthesis (PKAN)
- MT-ND: Mitochondrial genes (autonomic failure)
| Drug |
Target |
Application |
| Midodrine |
α1 agonist |
Orthostatic hypotension |
| Droxidopa |
Norepinephrine prodrug |
Neurogenic hypotension |
| Pyridostigmine |
AChE inhibitor |
Autoimmune dysautonomia |
| β-blockers |
β1 |
Resting tachycardia |
| Clonidine |
α2 agonist |
Hypertension, sweating |
- Non-pharmacological: Increased salt/fluid intake, compression stockings
- Fludrocortisone: Mineralocorticoid for volume expansion
- Ivabradine: If β-blockers insufficient
- 123I-MIBG scintigraphy: Cardiac sympathetic innervation
- Heart rate variability: Autonomic tone
- Tilt-table test: Orthostatic intolerance
- Sudomotor testing: Sweat function
- Gene therapy: Restore catecholamine synthesis
- Cell replacement: Sympathetic neuron transplantation
- Immunomodulation: For autoimmune autonomic neuropathy
- Alpha-synuclein targeting: Disease-modifying for PD
The study of Sympathetic 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.
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Goldstein DS, Sharabi Y. Neurogenic orthostatic hypotension: a pathophysiology update. Clin Auton Res. 2019;29(2):125-136. PMID:30610268
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Braak H, Saper CB. α-Synuclein in autonomic nervous system: a critical update. J Neural Transm (Vienna). 2019;126(10):1243-1251. PMID:31119402
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Kaufmann H, Goldstein DS. Autonomic dysfunction in Parkinson disease. Handb Clin Neurol. 2021;182:259-272. PMID:34161747
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Low PA, Benarroch EE. Clinical autonomic disorders. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2008.
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Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society criteria for the diagnosis of multiple system atrophy. Mov Disord. 2022;37(6):1131-1148. PMID:35354022
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Schmidt C, Herting B, Prieur S, et al. Autonomic dysfunction in patients with progressive supranuclear palsy. Mov Disord. 2019;34(11):1642-1652. PMID:31655093
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Ziemssen T, Reichmann H. Cardiovascular autonomic dysfunction in Parkinson disease. J Neurol Sci. 2010;289(1-2):74-80. PMID:19853051