Neurochemical Changes in the Hippocampus of the Brown Norway Rat During Aging

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.

Section: Fgf-2 + Cells In the Ca2 Subfield Of The Hippocampussupporting

confidence: 92%

Section: Introductionmentioning

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

“…In the hippocampus on the other hand, Long et al (1998) found no age related change in astrocytes and microglial cells in the aging mouse. Similarly, Bhatnagar et al (1997) found no increase in the total number of astrocytes in the hippocampus of rats, while Pilegaard and Ladefoged (1996) report a slight increase in number of astrocytes with age. Although there are some differences in these reports, the likely conclusion to be drawn is that in the cortices of normally aging rodents there is little, if any, significant increase in numbers of neuroglial cells with age.…”

Section: The Effects Of Age On Neuroglial Cells In Other Structuresmentioning

confidence: 94%

The neuroglial population in the primary visual cortex of the aging rhesus monkey

Peters

Verderosa

Sethares

2008

Glia

The effects of age on neuroglial cells have been examined in the primary visual cortices of rhesus monkeys that had been behaviorally tested. The assessment of changes in the neuroglial populations was made on the basis of the frequency of occurrence of profiles of neuroglial cells in semithick sections of osmicated tissue stained with toluidine blue. No changes were found in the numbers of astrocytes and microglial cells with age, but the numbers of oligodendrocytes increased by about 50%. The myelinated nerve bundles at the level of layer 4 were also examined by electron microscopy to assess the effects of age on the nerve fibers. The numbers of nerve fiber profiles showing age-related alterations in their myelin sheaths increase with age. There was also an age-related increase in the frequency of profiles of nerve fibers sectioned through paranodes, indicating that shorter lengths of myelin are being produced by remyelination. These changes in sheaths both correlate significantly with the frequency of oligodendrocyte profiles, suggesting that with age additional oligodendrocytes are required to remyelinate nerve fibers whose sheaths have broken down, probably by death of the original parent oligodendroglial cell. Also the most cognitively impaired monkeys had the greatest numbers of oligodendrocytes, but this is probably a secondary correlation, reflecting the fact that altered myelin slows down the rate of conduction along nerve fibers, which leads to cognitive decline.

J of Comparative Neurology

“…We also observed age-related reduction in FGF-2 expression levels throughout the rat brain (data not shown), which is in agreement with previous reports. Although there is no reduction in the total number of GFAP-positive cells, immunoreactivity for FGF-2 within individual glial cells is severely decreased with aging (Cintra et al, 1994;Bhatnagar et al, 1997). Such age-related decline in FGF-2 levels has been attributed to impaired FGF-2 synthesis by aged astrocytes (Shetty et al, 2005).…”

Section: Effects Of Aging On Fgfr-2 Expressionmentioning

confidence: 99%

Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR‐2) immunoreactivity in astrocytes of neurogenic and non‐neurogenic regions of the young adult and aged rat brain

Chadashvili

Peterson

2006

Fibroblast growth factors (FGFs) are polypeptides that exert diverse biological effects on many cell types and tissues during embryogenesis and adulthood. In the adult brain, FGF-2 is primarily expressed by astrocytes and select groups of neurons. It has been shown that FGF-2 is neuroprotective and can stimulate proliferation of NSCs in neurogenic regions of the adult mammalian brain. Cellular responses to FGFs are mediated through membrane-spanning tyrosine kinase receptors in conjunction with low affinity binding to heparin sulfate proteoglycans. Four FGF receptors (FGFR1-4) have been cloned and characterized to date. In this study, we describe the anatomical distribution of FGFR-2 in young and aged rat brains. We demonstrate that the olfactory bulb, hippocampus, and cerebellum display the most robust FGFR-2 expression and observed age-related decrease in FGFR-2 levels in some but not all brain regions. In addition, we identified astrocytes as the primary source of FGFR-2 expression using immunofluorescence confocal microscopy. The astrocyte populations in the neurogenic areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus, express high levels of FGFR-2 protein, which points to its possible involvement in neurogenesis. We also explored the role of FGFR-2 in response to perforant pathway lesion and observed enhanced FGFR-2 expression by astrocytes surrounding the lesion. Thus, FGF-2 biological effects on astrocytes appear to be mediated through FGFR-2-dependent mechanisms, and this may provide an indirect route by which FGF-2 acts on neuronal populations.