1. Neurogenesis occurs in the subventricular zone of the lateral ventricles in infants and adults. Neural stem cells and progenitor cells in the SVZ generate new neurons that migrate to other areas of the brain.
2. In infants, neuroblasts migrate from the SVZ to the olfactory bulb through the rostral migratory stream. Some cells branch off the RMS to supply the ventromedial prefrontal cortex.
3. There is evidence of declining neurogenesis with age as shown by a decrease in immature neurons in the RMS and olfactory tract between infants and adults. However, the existence of neurogenesis in the adult human brain remains an open question requiring further study.
2. What is Neurogenesis ?
Proliferation &
Stem Cell
Migration
Progenitor Cells
New neurons generated
from neural stem cells and
progenitors cells
Oligodendrocyte Astrocyte Neuron
11. Horizontal Section of the SVZ
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
12. Immunochemistry of the SVZ
During the first 18 months of age
Staining
Cells
Immature Neuron
Glia
Large number of DCX(+) neurons
populate the future gap layer
The glia cells processes fill the gap
area
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
13. Quantification of Immature Neuron in the SVZ
Staining
Immature neuron Proliferating subependymal cell
Sharp decline in proliferating cells and immature neuron
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
14. Conclusion
During infant and adult age
Infant Adult
Where these cells go ?
16. Caracterization of the RMS
At 5 months
Sagital and Coronal Reconstitution
Tributaries of
cells
Isolated
ependymal
islets
Evidence of the RMS between the SVZ
and the Olfactory Bulb (OB) Out of the
sagital plane
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
17. Immunohistochemistry of neurons in the RMS
At 5 months
Staining
Immature neuron
Tributaries of
Migrating neuron cells
Isolated
ependymal
islets
Out of the
sagital plane
Clusters of immature and migrating neurons
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
18. Immunohistochemistry and Electron Microscopie the RMS
At 1 week
Label
Immature neuron A : Immature neuron
Glia B : Glia
Individual DCX(+) neuronal chains Ultrastructural analysis of a neuronal
chain cross-section
Evidence of a chain of immature and migrating neurons within the RMS
surrounded by glia
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
20. Serial Coronal Sections of the Adult RMS
Staining
Cells
Glia
Zhengang Yang et al, Cell Research (2011) 21:1534-1550
21. Horizontal Section of the Adult RMS
Staining
Glia
Immature neuron
Cells
The RMS-like pathway exists in the adult human forebrain
Zhengang Yang et al, Cell Research (2011) 21:1534-1550
23. Immunohistochemistry in the Olfactory Tract
At 1 day,8 months, 7 years
Cross-Sectional Reconstitutions Staining
Immature neuron Cells
Migrating neuron
Decline of an active RMS
with age
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
24. Toluidine Blue Staining in a Longitudinal Section of the OT
At 6 months
Central chain of immature neurons surrounded by a matrix of
astrocytes
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
25. Quantification of cells in the Proximal and Distal RMS
At 6 months
Proximal RMS
Distal RMS
There is a decline in the total amount of cells and in
immature neurons between the proximal and distal RMS
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
26. Hypothesis for decline in cell number
At 6 Months
Staining
Immature neuron
Migrating and immature neuron
A medial migratory stream (MMS) of immature neurons branches from the
proximal rostral migratory stream (RMS) in the infant human brain to supply the
ventromedial prefrontal cortex (VMPFC)
Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487
28. Is really Neurogenesis over in the Human
adult brain ?
Other pathways like MMS
Serial sections (sagital, coronal, horizontal) : DAPI
If yes : Immunohistochemistry (DCX, Hud+/Sox10-, NeuN)
Apoptosis ?
Hybridation in-situ : caspase, P53 ?
Which are the transcription factors expressed by the astrocytes ?
Transcriptome : microarray
Hybridation in-situ for these transcription factor