Heat-Induced Antigen Retrieval: An Effective Method to Detect and Identify Progenitor Cell Types during Adult Hippocampal Neurogenesis

AbstractAdult hippocampal neurogenesis underpins learning, memory, and mood, but diminishes with age and illness. The orphan nuclear receptor TLX/NR2E1 is known to regulate neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is unknown. We found that neural stem and progenitor cells require monounsaturated fatty acids to survive and proliferate. Specifically, oleic acid (18:1ω9) binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell cycle and neurogenesis genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation. These findings pave the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.

Download Full-text

Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

Frontiers in Neuroscience ◽

10.3389/fnins.2021.689601 ◽

2021 ◽

Vol 15 ◽

Author(s):

Natalie N. Nawarawong ◽

K. Ryan Thompson ◽

Steven P. Guerin ◽

Chinchusha Anasooya Shaji ◽

Hui Peng ◽

...

Keyword(s):

Alcohol Dependence ◽

Dentate Gyrus ◽

Adult Neurogenesis ◽

Progenitor Cell ◽

Neural Progenitor Cell ◽

Neural Progenitor ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Female Rats ◽

Immature Neurons

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

Download Full-text

Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions

Scientific Reports ◽

10.1038/s41598-017-18184-2 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 3

Author(s):

Joanna M. Wasielewska ◽

Lisa Grönnert ◽

Nicole Rund ◽

Lukas Donix ◽

Ruslan Rust ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Immune Cells ◽

Cell Types ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Neural Precursor ◽

Chemical Mediator ◽

Physiological Conditions

Abstract There is growing evidence that both peripheral and resident immune cells play an important part in regulating adult neural stem cell proliferation and neurogenesis, although the contribution of the various immune cell types is still unclear. Mast cells, a population of immune cells known for their role in the allergic response, have been implicated in the regulation of adult hippocampal neurogenesis. Mast cell-deficient c-kitW-sh/W-sh mice have previously been shown to exhibit significantly decreased adult hippocampal neurogenesis and associated learning and memory deficits. However, given that numerous other cell types also express high levels of c-kit, the utility of these mice as a reliable model of mast cell-specific depletion is questionable. We show here, using a different model of mast cell deficiency (Mcpt5CreR26DTA/DTA), that precursor proliferation and adult neurogenesis are not influenced by mast cells in vivo. Interestingly, when applied at supraphysiological doses, mast cells can activate latent hippocampal precursor cells and increase subventricular zone precursor proliferation in vitro, an effect that can be blocked with specific histamine-receptor antagonists. Thus, we conclude that while both mast cells and their major chemical mediator histamine have the potential to affect neural precursor proliferation and neurogenesis, this is unlikely to occur under physiological conditions.

Download Full-text

Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201200035 ◽

2012 ◽

Vol 56 (8) ◽

pp. 1292-1303 ◽

Cited By ~ 51

Author(s):

Yanyan Wang ◽

Maoquan Li ◽

Xueqing Xu ◽

Min Song ◽

Huansheng Tao ◽

...

Keyword(s):

Cell Proliferation ◽

Green Tea ◽

Sonic Hedgehog ◽

Progenitor Cell ◽

Neural Progenitor Cell ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Sonic Hedgehog Pathway ◽

Pathway Activation ◽

Progenitor Cell Proliferation

Download Full-text

Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa)

Scientific Reports ◽

10.1038/s41598-021-04600-1 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Lena-Louise Schuele ◽

Britta Schuermann ◽

Andras Bilkei-Gorzo ◽

Sara Gorgzadeh ◽

Andreas Zimmer ◽

...

Keyword(s):

Adult Neurogenesis ◽

Cannabinoid Receptors ◽

Endocannabinoid System ◽

Cell Types ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Mouse Strains ◽

Specific Cell ◽

Experimental Conditions ◽

Diacylglycerol Lipase

AbstractThe endocannabinoid system modulates adult hippocampal neurogenesis by promoting the proliferation and survival of neural stem and progenitor cells (NSPCs). This is demonstrated by the disruption of adult neurogenesis under two experimental conditions: (1) NSPC-specific deletion of cannabinoid receptors and (2) constitutive deletion of the enzyme diacylglycerol lipase alpha (DAGLa) which produces the endocannabinoid 2-arachidonoylglycerol (2-AG). However, the specific cell types producing 2-AG relevant to neurogenesis remain unknown. Here we sought to identify the cellular source of endocannabinoids in the subgranular zone of the dentate gyrus (DG) in hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete Dagla either in neurons, or in astroglia and NSPCs. Surprisingly, neurogenesis was not altered in mice bearing a deletion of Dagla in neurons (Syn-Dagla KO), although neurons are the main source for the endocannabinoids in the brain. In contrast, a specific inducible deletion of Dagla in NPSCs and astrocytes (GLAST-CreERT2-Dagla KO) resulted in a strongly impaired neurogenesis with a 50% decrease in proliferation of newborn cells. These results identify Dagla in NSPCs in the DG or in astrocytes as a prominent regulator of adult hippocampal neurogenesis. We also show a reduction of Daglb expression in GLAST-CreERT2-Dagla KO mice, which may have contributed to the neurogenesis phenotype.

Download Full-text