Table 3.
Aging of the neurogenic microenvironment and its effects on neurogenesis
| Evolution with aging | Effect on neurogenesis in aged brain | |||
|---|---|---|---|---|
| Corticosteroids | Increase basal levelProlonged stress-induced secretion | (Sapolsky, 1992) | Acute ADX: increase of cell proliferation in the DG | (Cameron & McKay, 1999) |
| Increased expression of GR by precursors | (Garcia etal., 2004a) | Long-term ADX: increase of cell proliferation in the DG | ||
| Expression of MR by precursors | Inverse correlation between adrenal glands’ weight and proliferation or number of new neurons in the DG | (Montaron etal., 1999) (Montaron etal., 2006) (Montaron etal., 2006) | ||
| Neurosteroids | Acute Preg-S icv infusion: increase of cell proliferation in the DG | (Mayo etal., 2003) | ||
| Glutamate | NMDA-R antagonist ip injection: increase of the number of radial glia-like cells, proliferating cells and new neurons in the DG | (Nacher etal., 2003) | ||
| EGF signaling | Decrease of EGF-R expression in the SVZ (non-studied in DG) | (Enwere etal., 2004) | HB-EGF icv infusion: (3 days): increase of cell proliferation in the DG and the SVZ | (Jin etal., 2003a) (Enwere etal., 2004) |
| Decrease of TGFα expression in the SVZ (non-studied in DG) | EGF icv infusion (3 days): increase of cell proliferation in the SVZ | |||
| IGF-I | Decrease of IGF-I concentration Decrease of IGF-I receptor expression | (Sonntag etal., 1997) (Sonntag etal., 1999) (Lai etal., 2000) (Shetty etal., 2005) | IGF-I icv infusion (14 days): increase of cell proliferation in the DG | (Lichtenwalner etal., 2001) |
| FGF-2 | Decrease of hippocampal concentration of FGF-2 Decrease of FGFR-2 in the DG, the SVZ, the RMS, and the OB | (Shetty etal., 2005) (Chadashvili & Peterson, 2006) | FGF-2 icv infusion (3 days): strong increase of cell proliferation in the aged DG and the SVZ | (Jin etal., 2003a) |
| FGF-2 icv infusion (2 weeks): increase of both cell proliferation and dendritic growth in middle-aged DG | (Rai etal., 2007) | |||
| Vasculature and VEGF | Decrease of cerebral microvasculature (especially marked in DG) | (Riddle etal., 2003) (Hattiangady & Shetty, 2008) | ? | |
| Decrease of microvascular plasticity | (Sonntag etal., 1997) | |||
| Increase of the distance between precursors and blood vesselsReduced VEGF synthesis | (Shetty etal., 2005) (Hattiangady & Shetty, 2008) | |||
| Cell cycle regulators | Increase of p16INK4a expression (undetectable in young animals) | (Molofsky etal., 2006) | Bmi-1 KO mice′: premature senescence of NSC and decrease of proliferation in SVZ, the phenotype is rescued by p16INK4a or p19Arf deletion | (Molofsky etal., 2005) (Bruggeman etal., 2005) |
| P16INK4a KO mice: proliferation is increased in SVZ but not DG of aged mice | (Molofsky etal., 2006) | |||
DG, dentate gyrus; EGF, epidermal growth factor; FGF, fibroblast growth factor; IGF-I, insulin-like growth factor-I; icv, intracerebroventricular; OB, olfactory bulb; Preg-S, pregnenolone sulfate; RMS, rostral migratory stream; SVZ, subventricular zone; VEGF, vascular endothelial growth factor.