Biology subjects

Rieskamp, J. D.

Publications and source records attributed to Rieskamp, J. D..

4 recordsLinked to original sources

bioRxiv2023

Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion.

Adult neural stem and progenitor cells (NSPCs) reside in the dentate gyrus (DG) of the hippocampus throughout the lifespan of most mammalian species. In addition to generating new neurons, NSPCs may alter their niche via secretion of growth factors and cytokines. We recently showed that adult DG NSPCs secrete vascular endothelial growth factor (VEGF), which is critical for maintaining adult neurogenesis. Here, we asked whether NSPC-derived VEGF alters hippocampal function independent of adult neurogenesis. We found that loss of NSPC-derived VEGF acutely impaired hippocampal memory, caused neuronal hyperexcitability and exacerbated excitotoxic injury. We also found that NSPCs generate substantial proportions of total DG VEGF and VEGF disperses broadly throughout the DG, both of which help explain how this anatomically-restricted cell population could modulate function broadly. These findings suggest that NSPCs actively support and protect DG function via secreted VEGF, thereby providing a non-neurogenic functional dimension to endogenous NSPCs.

neuroscience↗

bioRxiv2022

Excitatory amino acid transporter 1 supports adult hippocampal neural stem cell self-renewal.

Within the adult mammalian dentate gyrus (DG) of the hippocampus, glutamate stimulates neural stem cell (NSC) self-renewing proliferation, providing a link between adult neurogenesis and local circuit activity. Here, we show that glutamate-induced self-renewal of adult DG NSCs requires glutamate transport via excitatory amino acid transporter 1 (EAAT1) to stimulate lipogenesis. Loss of EAAT1 prevented glutamate-induced self-renewing proliferation of NSCs in vitro and in vivo, with little role evident for canonical glutamate receptors. Transcriptomics and further pathway manipulation revealed that glutamate simulation of NSCs relied on EAAT1 transport-stimulated lipogenesis. Our findings demonstrate a critical, direct role for EAAT1 in stimulating NSCs to support neurogenesis in adulthood, thereby providing insights into a non-canonical mechanism by which NSCs sense and respond their niche.

neuroscience↗

bioRxiv2021

Intracrine Vascular Endothelial Growth Factor Maintains Hippocampal Neural Stem Cell Quiescence

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 vascular endothelial growth factor (VEGF), a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that NSC-specific VEGF loss led to dissociation of NSCs from local vasculature but surprisingly found no changes in vascular density. Instead, we found that NSC-derived VEGF supports the motility of NSCs themselves via a cell internal signaling loop. We further found that this internal autocrine loop also independently maintained NSC quiescence cell autonomously. Combined, our findings suggest that NSCs maintain their populations via 2 mechanisms that are dependent on cell internal VEGF signaling: self-stimulated motility towards vasculature and cell autonomous maintenance of quiescence programs.

neuroscience↗

bioRxiv2019

Stereological characterization of the major cell lineages in the mouse dorsal dentate gyrus

Adult neurogenesis in the dorsal dentate gyrus (DG) subregion of the mammalian hippocampus supports critical cognitive processes related to memory. Local DG cell populations form a neurogenic niche specialized to regulate adult neurogenesis. Recently, DG astrocytes, microglia, endothelia, and neural stem cells have been identified as sources of neurogenesismodulating secreted factors. Accurately estimating the size of these cell populations is useful for elucidating their relative contributions to niche physiology. Previous studies have characterized these cell types individually, but to our knowledge no comprehensive study of all these cell types exists. This is problematic because considerable variability in reported population size complicates comparisons across studies. Here, we apply consistent stereological methods within a single study to estimate cell density for neurogenesis-modulating secretory cell types in the dorsal DG of adult mice. We used immunohistochemical phenotypic markers to quantify cell density and found that stellate astrocytes were the most numerous followed by endothelia, intermediate progenitors, microglia, and neural stem cells. We did not observe any significant sex differences in cell density. We expect our data will facilitate efforts to elucidate the role of DG secretory cell populations in regulating adult neurogenesis.

neuroscience↗