Delayed angiogenesis in aging rats and therapeutic effect of adenoviral gene transfer of VEGF

2008

Neurobiology of Aging

222

207

To investigate whether dramatically waned dentate neurogenesis during aging is linked to diminution in neural stem/progenitor cell (NSC) number, we counted cells immunopositive for Sox-2 (a putative marker of NSCs) in the subgranular zone (SGZ) of young, middle-aged and aged F344 rats. The young SGZ comprised ~50,000 Sox-2 + cells and this amount did not diminish with aging. Quantity of GFAP + cells and vimentin + radial glia also remained stable during aging in this region. Besides, in all age groups, analogous fractions of Sox-2 + cells expressed GFAP (astrocytes/NSCs), NG-2 (oligodendrocyte-progenitors/NSCs), vimentin (radial glia), S-100β (astrocytes) and doublecortin (new neurons). Nevertheless, analyses of Sox-2 + cells with proliferative markers insinuated an increased quiescence of NSCs with aging. Moreover, the volume of rat-endothelial-cell-antigen-1 + capillaries (vascular-niches) within the SGZ exhibited an age-related decline, resulting in an increased expanse between NSCs and capillaries. Thus, decreased dentate neurogenesis during aging is not attributable to altered number or phenotype of NSCs. Instead, it appears to be an outcome of increased quiescence of NSCs due to changes in NSC milieu.

Section: Relationship Between Decreased Vascular Niches In the Sgz Ansupporting

confidence: 54%

Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus

Hattiangady

2008

Neurobiology of Aging

222

207

“…The concentration of VEGF also increases in conditions such as hypoxia and ischemia, and hence VEGF is thought to play an important role in hypoxia-induced cerebral angiogenesis (Shweiki et al, 1992;LaManna et al, 1998). Further, aging is generally associated with declined endothelial cell proliferation and reduced endogenous VEGF production (Wang et al, 2004), and degenerative changes in endothelial cells and pericytes (Ueno et al, 1998). From the above perspectives, it appears that greatly declined VEGF concentration in the hippocampus at middle age is linked to multiple changes in the cellular substrates for VEGF, which may include reduced proliferation of endothelial cells in capillaries and degeneration of endothelial cells and pericytes, particularly in the vascular niche surrounding stem/progenitor cells (Palmer et al, 2000).…”

Section: Extent Potential Reasons and Consequences Of Age-related Rmentioning

confidence: 99%

Stem/progenitor cell proliferation factors FGF‐2, IGF‐1, and VEGF exhibit early decline during the course of aging in the hippocampus: Role of astrocytes

Hattiangady

2005

Glia

273

210

Dentate neurogenesis, important for learning and memory, declines dramatically by middle age. Although studies have shown that this age-related decrease can be reversed to some extent by exogenous applications of mitogenic factors, it is unclear whether one or more of these factors exhibits decline by middle age. We hypothesize that multiple stem/progenitor cell proliferation factors exhibit early decline during the course of aging in the hippocampus, and some of these declines are linked to age-related alterations in hippocampal astrocytes. We measured the concentrations of fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) in the hippocampus of young, middle-aged, and aged F344 rats, using enzyme-linked immunosorbent assay (ELISA). In addition, we quantified the total number of FGF-2 immunopositive (FGF-2+) and glial fibrillary acidic protein immunopositive (GFAP+) cells in the dentate gyrus and the entire hippocampus. Our results provide new evidence that the concentrations of FGF-2, IGF-1, and VEGF decline considerably by middle age but remain steady between middle age and old age. Further, decreased concentrations of FGF-2 during aging are associated with decreased numbers of FGF-2+ astrocytes. Quantification of GFAP+ cells, and GFAP and FGF-2 dual immunostaining analyses, reveal that aging does not decrease the total number of astrocytes but fractions of astrocytes that express FGF-2 decline considerably by middle age. Thus, dramatically decreased dentate neurogenesis by middle age is likely linked to reduced concentrations of FGF-2, IGF-1, and VEGF in the hippocampus, as each of these factors can individually influence the proliferation of stem/progenitor cells in the dentate gyrus. Additionally, the results demonstrate that decreased FGF-2 concentration during aging is a consequence of age-related impairment in FGF-2 synthesis by astrocytes.

J Cereb Blood Flow Metab

“…However, it is not known if aging induces changes in nigral vascularization similar to those reported for PD. Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis, and is thought to be involved in aging-induced deterioration of angiogenesis in several tissues (Iemitsu et al, 2006;Wang et al, 2004), as well as in vascular changes observed in PD and PD animal models (Barcia et al, 2005;Wada et al, 2006). Furthermore, several recent studies have shown that VEGF is a highly potent neuroprotective and neurorescue molecule for DA neurons (Yasuhara et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Aging and Sedentarism Decrease Vascularization and VEGF Levels in the Rat Substantia Nigra. Implications for Parkinson's Disease

Villar-Cheda

Sousa-Ribeiro

Rodríguez‐Pallares

et al. 2008

It is not known if aging induces changes in nigral vascularization and nigral vascular endothelial growth factor (VEGF) levels similar to those previously reported for Parkinson's disease (PD). In this study nonexercised rats displayed age-dependent decreases in the density of nigral microvessels and VEGF mRNA expression, which were reversed by physical exercise. Such changes may enhance the vulnerability of dopaminergic neurons and the risk of developing PD, and may be reduced by exercise. Furthermore, the observed pattern is the opposite of that previously observed in PD, suggesting that the process underlying PD is not an accelerated age-dependent decline in the dopaminergic system.