1. Neurogenesis
in the adult CNS
What is it?
Defined as: The ‘birth of new neurons’
Overview:
History
Where does it occur
How are new neurons generated
Migration
Method of investigation
Regulation by factors
2. +
History
Before 1950’s: belief that no new neurons were generated in the
brain
1950’s: New technique developed for labeling cells during division
[H3]-Thymidine is a marker for S-phase in the cell cycle.
1961 – Using this technique, the first evidence of neurogenesis was
discovered in 3 day old mice
1980’s: New neurons found to receive synaptic inputs and extended
their own axon projections to target areas
- Bromodeoxyuridine (BrdU) is another S-phase marker
1998 – Using BrdU, neurogenesis found in adult humans
Neurogenesis in adult CNS
2
Guo-li Ming, 2005
3. +
Where does neurogenesis occur?
Subgranular Zone
Found between the Hilus
and Granule cell layer of
the Dentate gyrus in the
Hippocampus.
Contains:
SGV astrocytes
Precursor cells
granule neurons
Subventricular Zone
Found along the wall of
the lateral ventricle as
as layer of dividing cells
Contains:
Neuroblasts
SVZ astrocytes
Immature precursors
Figure 1 and 2 Guo-li Ming, 2005
4. +
How are new neurons generated?
In the SVZ:
In rodents:
SVZ astrocytes (blue)
precursor cells (green)
neuroblasts (red)
Remains to be determined if
these astrocytes give rise to
neurons in adult humans
(Guo-li Ming, 2005)
BL = basal lamina BV = blood vessel
LV = lateral ventricle E = endothelial cells
Figure 2 Fiona Doetsch, 2003
5. +
How are new neurons generated?
In the SGZ:
Neural
stem cells
Dividing
cells
Immature
neurons
Dentate
Gyrus
granule cell
layer
SGZ astrocytes Progenitor cells Neuroblasts
(dividing cells) (immature
neurons)
Figure 3. Jessica L. Ables, J.neurosci. 2008
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Method of Investigation
BrdU = Bromodeoxyuridine [H3]-T = [H3]-thymidine
‘U’ ‘T’
Synthesizing DNA
U T
Limits:
nucleotide analogs Tissue fixation and DNA denature
sequentially used can’t analyse live cells
Incorporation = S-phase only
could misidentify repairing/dying
cells for new neurons
Guo-li Ming, 2005
9. +
What regulates adult neurogenesis?
Regulated by various environmental factors
Inhibits adult neurogenesis:
(1) Age (SGZ/SVZ)
(2) Stress (acute or chronic)
affects proliferation and maturation
(3) Sleep, chronic (may contribute to depression)
(4) Microglia activation
(5) Inflammation
Increase adult neurogenesis:
(6) Exercise (SGZ)
(7) Antidepressants (SGZ) – prevent/reverse (2)
(8) Microglia activation
P.J Lucassen et. All 2010
10. +
Summary
New neurons come to neural stem cells in the subventricular zone and
subgranular zone
Astrocyte in SVZ/SGZ Precursor cell Neuroblast matured neuron
The neuroblasts migration through glial tubes made by the astrocytes
and form the Rostral Migratory Stream towards to Olfactory Bulb
BrdU and [H3]-Thymidine are used as S-phase markers to trace cellular
division
There are many endogenous and exogenous factors that regulate
neurogenesis.
11. +
References
1) Figure 1 and 2 of SVZ/SGZ – Fiona Doetsch, Current Opinion
in Genetics and Development, 2003.
2) Figure 3 of SGZ in hippocampus – Jessica L. Ales, journal of
neuroscience, 2008
3) Figure 4 Julieta G. Mendoza-Torreblanca, 2008
4) Guo-li Ming, 2005 ‘Adult neurogenesis in the mammalian
central nervous system’ Annua Review of Neuroscience, 2005
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History
Before 1950’s: belief that no new neurons were generated in the
brain
1950’s: New technique developed for labeling cells during division
[H3]-Thymidine is a marker for S-phase in the cell cycle.
1961 – Using this technique, the first evidence of neurogenesis was
discovered in 3 day old mice
1980’s: New neurons found to receive synaptic inputs and extended
their own axon projections to target areas
- Bromodeoxyuridine (BrdU) is another S-phase marker
1998 – Using BrdU, neurogenesis found in adult humans
Neurogenesis in adult CNS
2
Guo-li Ming, 2005](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)