Autocrine VEGF drives neural stem cell proximity to the adult hippocampus vascular niche.

The vasculature is a key component of adult brain neural stem cell (NSC) niches. In the adult mammalian hippocampus, NSCs reside in close contact with a dense capillary network. How this niche is maintained is unclear. We recently found that adult hippocampal NSCs express VEGF, a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that global and NSC-specific VEGF loss led to dissociation of NSCs and their intermediate progenitor daughter cells from local vasculature. Surprisingly, though, we found no changes in local vascular density. Instead, we found that NSC-derived VEGF supports maintenance of gene expression programs in NSCs and their progeny related to cell migration and adhesion. In vitro assays revealed that blockade of VEGF receptor 2 impaired NSC motility and adhesion. Our findings suggest that NSCs maintain their own proximity to vasculature via self-stimulated VEGF signaling that supports their motility towards and/or adhesion to local blood vessels.

The neural stem cell secretome across neurodevelopment.

Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In addition to their ability to produce new cells, NSCs secrete a variety of products, known collectively as the NSC secretome, that have been shown to ameliorate CNS disease pathology and promote recovery. As pre-clinical and clinical research to harness the NSC secretome for therapeutic purposes advances, a more thorough understanding of the endogenous NSC secretome can provide useful insight into the functional capabilities of NSCs. In this review, we focus on research investigating the autocrine and paracrine functions of the endogenous NSC secretome across life. Throughout development and adulthood, we find evidence that the NSC secretome is a critical component of how endogenous NSCs regulate themselves and their niche. We also find gaps in current literature, most notably in the clinically-relevant domain of endogenous NSC paracrine function in the injured CNS. Future investigations to further define the endogenous NSC secretome and its role in CNS tissue regulation are necessary to bolster our understanding of NSC-niche interactions and to aid in the generation of safe and effective NSC-based therapies.

Aging gracefully: social engagement joins exercise and enrichment as a key lifestyle factor in resistance to age-related cognitive decline.

Cognitive impairment is a consequence of the normal aging process that effects many species, including humans and rodent models. Decline in hippocampal memory function is especially prominent with age and often reduces quality of life. As the aging population expands, the need for interventional strategies to prevent cognitive decline has become more pressing. Fortunately, several major lifestyle factors have proven effective at combating hippocampal aging, the most well-known of which are environmental enrichment and exercise. While the evidence supporting the beneficial nature of these factors is substantial, a less well-understood factor may also contribute to healthy cognitive aging: social engagement. We review the evidence supporting the role of social engagement in preserving hippocampal function in old age. In elderly humans, high levels of social engagement correlate with better hippocampal function, yet there is a dearth of work to indicate a causative role. Existing rodent literature is also limited but has begun to provide causative evidence and establish candidate mechanisms. Summed together, while many unanswered questions remain, it is clear that social engagement is a viable lifestyle factor for preserving cognitive function in old age. Social integration across the lifespan warrants more investigation and more appreciation when designing living circumstances for the elderly.