VEGF is necessary for exercise‐induced adult hippocampal neurogenesis

Abstract

Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic-pituitary-adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a 'somatic regulator' of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

“…However, overall, BACE2 is present in low levels in the brain [3,36] and within select subcortical brain nuclei and not as ubiquitously expressed as BACE1. Further, a recent paper suggests that the cleavage site on APP of BACE2 may be more consistent with alpha-secretase activity [12]. We also would have predicted that had BACE2 been a significant contributor to Aβ production in DS, then beta-secretase activity may have been significantly higher than controls; our observations did not support this hypothesis.…”

Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation

“…In various animal models, VEGF stimulates the proliferation of NSCs and neurogenesis in the CNS, such as the hippocampus [15,16]. In adult hippocampus and the subventricular zone, NSCs are found in close proximity to blood vessels and surrounded by glial cells.…”

“…In most occasions, VEGF exerts its action via its receptor, Flk-1, in endothelial cells, hematopoietic stem/progenitor cells and some tumor cells [11][12][13][14]. In the central nervous system (CNS), for instance the hippocampus, VEGF stimulates the expansion of NSCs and neurogenesis in various animal models, resulting in improved learning ability [15][16][17][18]. In adults, NSCs are found in close proximity to blood vessels and surrounded by glial cells in the hippocampus and the subventricular zone.…”

Adult Neurogenesis and the Ischemic Forebrain

“…Odor enrichment, conversely, has no effect on DGC production but enhances the survival of newly generated neurons in the olfactory bulb (Rochefort et al, 2002), and odor deprivation via unilateral naris closure reduces the number of surviving adult-born olfactory interneurons (Corotto et al, 1994). Growth factors might have a significant role in mediating these effects, since environmental enrichment increases hippocampal levels of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF; Young et al, 1999), and blocking brain uptake of IGF-1 or vascular endothelial growth factor (VEGF) prevents the increase in DGC production induced by enrichment or exercise (Trejo et al, 2001;Fabel et al, 2003;Cao et al, 2004).…”