ADULT AND INFANT

Neurogenesis

Inés Cordón & Ingrid Meucci

New neurons generated from neural stem cells and progenitors cells

Oligodendrocyte Astrocyte Neuron

Stem Cell Proliferation & Migration

What is Neurogenesis ?

Progenitor Cells

Lateral Ventricle

Hippocampus

Where does Neurogenesis happen?

The SVZ : SubVentricular ZoneIn Adult

The RMS : Rostral Migratory Stream

Evidence of Migration in Rodent

DOES NEUROGENESIS

DISAPPEAR ?

Technique: Immunohistochemistry

Stains Mark

DAPI All Cells

DCX : Doublecortin Immature neuron

PSA-NCAM Migrating neuron

Ki67 Cellular proliferation

GFAP/Vimentine Astrocytes/Glia

Neurogenesis in Human

Subventricular Zone1

Rostral Migratory Stream2

Olfactory Tract3

Lateral ventricle

Neuroblasts

Olfactory Bulb

1. Neurogenesis in the SVZ

Horizontal Section of the SVZ

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

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

Immunochemistry of the SVZ

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

Immature neuron Proliferating subependymal cell

Staining

Sharp decline in proliferating cells and immature neuron

Quantification of Immature Neuron in the SVZ

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

During infant and adult age

Conclusion

Infant Adult

Where these cells go ?

2. Neurogenesis in the RMS

At 5 months

Sagital and Coronal Reconstitution

Tributaries of cells

Isolated ependymal

islets

Out of the sagital plane

Caracterization of the RMS

Evidence of the RMS between the SVZ and the Olfactory Bulb (OB)

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

At 5 months

Staining

Migrating neuron

Immature neuronTributaries of

cells

Isolated ependymal

islets

Out of the sagital plane

Immunohistochemistry of neurons in the RMS

Clusters of immature and migrating neurons

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

At 1 week

Individual DCX(+) neuronal chains Ultrastructural analysis of a neuronal chain cross-section

Label

Glia

Immature neuron A : Immature neuron

B : Glia

Immunohistochemistry and Electron Microscopie the RMS

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

General Structure of the RMS

Serial Coronal Sections of the Adult RMS

Zhengang Yang et al, Cell Research (2011) 21:1534-1550

Staining

Cells

Glia

Horizontal Section of the Adult RMS

The RMS-like pathway exists in the adult human forebrain

Zhengang Yang et al, Cell Research (2011) 21:1534-1550

Staining

Immature neuron

Glia

Cells

3. Neurogenesis in the Olfactory Tract

At 1 day,8 months, 7 years

Cross-Sectional Reconstitutions Staining

Migrating neuron

Immature neuron Cells

Immunohistochemistry in the Olfactory Tract

Decline of an active RMS with age

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

Toluidine Blue Staining in a Longitudinal Section of the OT

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

At 6 months

At 6 months

Quantification of cells in the Proximal and Distal RMS

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

At 6 Months

Hypothesis for decline in cell number

Staining

Migrating and immature neuron

Immature neuron

Arturo Alvarez- Buylla et al, Nature. ; 478(7369): 382–386. doi:10.1038/nature10487

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)

Summary

Lateral ventricle

Subventricular Zone

Rostral Migratory Stream

Neuroblasts

Olfactory Tract

Olfactory Bulb

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

Thank For Your Attention