Adult Neurogenesis Is Regulated by Endogenous Factors Produced During Neurodegeneration

Abstract

Abstract. Adult neurogenesis is the process of generating new neurons that become integrated into existing circuits after fetal and early postnatal development has ceased. In most mammalian species, adult neurogenesis only appears to occur in the olfactory bulb and the hippocampus, where neural stem/progenitor cells (NPCs) exist to create new neurons. In adult neurogenesis, microenviromental change is thought to provide a specific modulation for maintaining the multi-potent state of these NPCs. Neurodegeneration is driven by the activation of resident microglia, astrocytes, and infiltrating peripheral macrophages, which release a plethora of cytokines, chemokines, neurotransmitters, and reactive oxygen species. These endogenous factors cause further bystander damage to neurons and produces both detrimental and favorable conditions for neurogenesis. Interestingly, these endogenous factors also affect the proliferation, migration, differentiation, and survival of the NPCs, as well as regulate the incorporation of newly formed neurons into the brain circuitry. The unique profile of the endogenous factors released can vary the degree of neuroregeneration after neurodegeneration. This current review summarizes recent knowledge in the emerging field that is showing that adult neurogenesis is regulated by endogenous factors produced during neurodegeneration.

Glycine transporter-1 regulates the proliferation of neural stem/progenitor cells derived from the embryonic mouse hippocampus

“…Thus, it has been proposed that neurotransmitters may act directly as paracrine or autocrine factors to NPCs under physiological conditions. Indeed, systemic administration of NMDA decreases proliferation of NPCs in the adult murine hippocampal dentate gyrus [29], whereas administration of a dopamine D3 agonist increased proliferation of NPCs in the adult murine subventricular zone [28]. In the present study, we demonstrated the possibility that glycine enhances proliferation of NPCs.…”

Deficiency of Adult Neurogenesis in the Ts65Dn Mouse Model of Down Syndrome

“…The subventricular zone, subgranular layer of the dentate gyrus (DG), and cortex are the main sites of adult neurogenesis (Gould et al, 1999;Luskin & Boone, 1994;Palmer et al, 2000;Seki et al, 2007;Yoneyama et al, 2011). Newly-born neurons during adult neurogenesis have the ability to integrate into previously established neuronal networks (Kee et al, 2007;Markakis & Gage, 1999;Sandoval et al, 2011).…”

“…Newly-born neurons during adult neurogenesis have the ability to integrate into previously established neuronal networks (Kee et al, 2007;Markakis & Gage, 1999;Sandoval et al, 2011). Alteration of neurogenesis under different experimental and pathological conditions has been described to a great extent (Rodriguez & Verkhratsky, 2011;Sandoval et al, 2011;Winner et al, 2011;Yoneyama et al, 2011;Yu et al, 2009). Significant decreases of neurogenesis have been found in neurodevelopmental (Contestabile et al, 2007;Guidi et al, 2008Guidi et al, , 2010 and in neurodegenerative diseases (Rodriguez & Verkhratsky, 2011).…”

Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

“…Similarly, cytokines/chemokines and other pro-and anti-inflammatory molecules have been shown to regulate NSC/NPC survival, proliferation, fate, and migration (reviewed in Ref. 19). However, the effect of infiltrating innate immune cells and humoral components of the innate immune response, for example, neutrophils, macrophages (Mf), and cytokines/ proteins of the complement cascade, on stem cells remains to be elucidated.…”