| Lineage |
Neuron > Progenitor > Neuroblast |
| Neurotransmitters |
GABA (tonic), Glutamate (subpopulations) |
| Markers |
DCX, PSA-NCAM, Nestin, Sox2, Tuj1 (βIII-tubulin) |
| Brain Regions |
Subventricular Zone, Rostral Migratory Stream, Olfactory Bulb |
| Disease Vulnerability |
Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Brain Injury |
The rostral migratory stream (RMS) is the principal pathway for neurogenesis in the adult mammalian brain. This stream of migrating neuroblasts originates in the subventricular zone (SVZ) of the lateral ventricles and travels through the RMS to reach the olfactory bulb, where they differentiate into interneurons.[1]
This adult neurogenic pathway has significant implications for neurodegenerative diseases, as endogenous neural stem cells represent potential therapeutic targets for brain repair.[2]
The RMS represents one of two major neurogenic niches in the adult mammalian brain:
- Subventricular Zone (SVZ): The largest neurogenic region in the adult brain, located along the lateral ventricles
- Rostral Migratory Stream: A pathway of tangentially migrating neuroblasts
- Olfactory Bulb: Final destination where cells differentiate into various interneuron subtypes
- Continuous neurogenesis: Produces thousands of new neurons daily in rodents, hundreds in humans
- Tangential migration: Cells migrate in chains through the RMS rather than radially
- Linear pathway: RMS travels from the SVZ through the striatum to the olfactory bulb
- Cellular composition: Predominantly doublecortin (DCX)-positive neuroblasts
¶ Anatomy and Morphology
The RMS traverses several brain regions:
- SVZ: Neurogenic niche lining the lateral ventricles
- Corpus callosum: Initial trajectory through white matter
- Striatum: Passes through the ventral striatum
- Olfactory tract: Terminates in the olfactory bulb
Neuroblasts in the RMS exhibit:
- Cell body: Small, elongated (8-15 μm)
- Leading process: Elongated dendritic process toward the olfactory bulb
- Trailing process: Short trailing axon
- Migratory morphology: Characteristic elongated "chains" of cells
- Speed: 50-100 μm/day in rodents
- Directionality: Guided by chemotropic cues
- Chain migration: Cells migrate in close association with each other
- Saltatory movement: Intermittent bursts of movement
- Immature excitability: Voltage-gated sodium and potassium currents develop as cells approach the olfactory bulb
- GABAergic signaling: GABA provides crucial trophic support during migration
- Calcium dynamics: Transient calcium elevations associated with process extension
| Marker |
Expression |
Function |
| Doublecortin (DCX) |
High |
Microtubule-associated protein, migration |
| PSA-NCAM |
High |
Polysialylated neural cell adhesion molecule |
| Nestin |
Intermediate |
Neural stem cell marker |
| Sox2 |
Variable |
Transcription factor, stemness |
| Tuj1 (βIII-tubulin) |
High |
Neuronal differentiation marker |
- SLIT/ROBO guidance: Chemorepulsive signaling directing migration
- NEGF/EGFR: Epidermal growth factor promotes proliferation
- Shh signaling: Sonic hedgehog influences SVZ neurogenesis
- Wnt/β-catenin: Posterior signaling that becomes anterior-inhibited
The RMS/OB system shows alterations in AD:[3]
- Reduced neurogenesis: Decreased SVZ proliferation in AD models and patients
- Olfactory dysfunction: Early olfactory deficits correlate with RMS dysfunction
- Amyloid effects: Aβ impairs neuroblast migration and survival
- Tau pathology: Tau accumulates in RMS region in AD brains
- Therapeutic potential: Enhancing neurogenesis as therapeutic strategy
- SVZ changes: Altered neurogenesis in PD models
- Olfactory impairment: Early non-motor symptom in PD
- Dopaminergic modulation: Dopamine influences SVZ proliferation
- α-Synuclein effects: May impair neuroblast function
- Cell replacement potential: Potential for dopaminergic neuron replacement
- Enhanced neurogenesis: Compensatory increase in some HD models
- Migration defects: Altered RMS function in HD
- Therapeutic targeting: Stem cell-based therapies under investigation
¶ Brain Injury and Stroke
- Injury-induced neurogenesis: Increased proliferation following brain injury
- Migration to damage sites: Potential for endogenous repair
- Therapeutic enhancement: Growth factor administration to boost repair
- Physical activity: Exercise increases SVZ proliferation and RMS neurogenesis
- Environmental enrichment: Cognitive stimulation promotes neurogenesis
- Pharmacological approaches: Growth factors, antidepressants
- Dietary interventions: Caloric restriction, specific nutrients
- Transplantation: SVZ-derived or induced neural stem cells
- Gene therapy: Modulating neurogenic pathways
- Biomaterial scaffolds: Guiding migration to target regions
- Combination approaches: Cell + factor delivery
The rostral migratory stream represents a critical adult neurogenic pathway with significant implications for neurodegenerative disease. Understanding and manipulating this endogenous repair mechanism offers potential therapeutic strategies for AD, PD, HD, and traumatic brain injury. While significant challenges remain, the RMS continues to be an active area of research for brain repair and regeneration.
The study of Rostral Migratory Stream Neuroblasts 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.
- Lois C, et al. Chain formation in the adult mouse subventricular zone. J Neurosci. 1996.
- Alvarez-Buylla A, et al. The rostral migratory stream in adult brain. Cell Stem Cell. 2021.
- Winner B, et al. Adult neurogenesis and neurodegenerative disease. Nat Rev Neurosci. 2022.
- Curtis MA, et al. Human neuroblasts migrate to the olfactory bulb. J Comp Neurol. 2007.
- Höglinger GU, et al. Neurogenesis in neurodegenerative disease. Nat Rev Neurol. 2023.
- Sawada M, et al. Neural stem cells in Parkinson's disease. Prog Neurobiol. 2021.
- Sorrells SF, et al. Human hippocampal neurogenesis drops sharply in children. Nature. 2018.
- Gage FH. Adult neurogenesis in mammals. Science. 2019.