Faculty Opinions recommendation of Comparison of adult hippocampal neurogenesis and susceptibility to treadmill exercise in nine mouse strains.

The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis.

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Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains

Genes Brain & Behavior ◽

10.1111/j.1601-183x.2010.00674.x ◽

2011 ◽

Vol 10 (3) ◽

pp. 345-353 ◽

Cited By ~ 65

Author(s):

P. J. Clark ◽

R. A. Kohman ◽

D. S. Miller ◽

T. K. Bhattacharya ◽

W. J. Brzezinska ◽

...

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Genetic Influences ◽

Mouse Strains ◽

Exercise Induced

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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.

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Autocrine regulation of adult neurogenesis by the endocannabinoid 2-arachidonoylglycerol (2-AG)

10.1101/2021.02.11.430731 ◽

2021 ◽

Author(s):

Lena-Louise Schuele ◽

Britta Schürmann ◽

Andras Bilkei-Gorzo ◽

Andreas Zimmer ◽

Este Leidmaa

Keyword(s):

Progenitor Cells ◽

Endocannabinoid System ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Mouse Strains ◽

Neuronal Stem Cells ◽

Neurogenic Niche ◽

Neuronal Progenitor Cells ◽

Neuronal Progenitor ◽

Cellular Source

AbstractThe endocannabinoid system (ECS) modulates adult hippocampal neurogenesis by promoting the proliferation and survival of progenitor cells. Specifically, deleting cannabinoid CB1 receptors on neuronal stem cells (NSCs) or the constitutive deletion of the endocannabinoid 2-arachidonoylglycerol (2-AG) producing enzyme diacylglycerol lipase alpha (DAGLa) disrupts adult hippocampal neurogenesis. However, it is not known which cells are the producers of 2-AG relevant to neurogenesis. In this paper, we investigated the cellular source of endocannabinoids in the subgranular zone (SGZ) of the hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete DAGLa either in neurons or astroglia and neuronal progenitor cells. Surprisingly, neurogenesis was not altered in mice with a specific deletion of Dagla in neurons (Syn-Dagla KO), although these cells are the main source for the endocannabinoids in the brain. In contrast, mice with a specific inducible deletion of Dagla in neuronal progenitor cells and astrocytes (GLAST-CreERT2-Dagla KO) showed a strongly impaired neurogenesis with significantly reduced proliferation and survival of newborn cells. These results identify Dagla in neuronal progenitor cells in the SGZ of dentate gyrus or in astrocytes, as the cellular source for 2-AG in adult hippocampal neurogenesis. In summary, 2-AG produced by progenitor cells or astrocytes in the SGZ regulates adult hippocampal neurogenesis. The implications of these findings and the depressive-like phenotype in Dagla-deficient genetic mouse models are discussed.

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Treadmill Exercise Ameliorates Adult Hippocampal Neurogenesis Possibly by Adjusting the APP Proteolytic Pathway in APP/PS1 Transgenic Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22179570 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9570

Author(s):

Haizhen Yu ◽

Chenfei Zhang ◽

Jie Xia ◽

Bo Xu

Keyword(s):

Learning And Memory ◽

Molecular Mechanisms ◽

Treadmill Exercise ◽

Neurodegenerative Disorder ◽

The Elderly ◽

Memory Capacity ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Related Factors ◽

Proteolytic Pathway

Alzheimer’s disease (AD) is a neurodegenerative disorder known to cause cognitive impairment among the elderly worldwide. Although physical exercise-induced adult hippocampal neurogenesis (AHN) improves cognition, understanding its underlying molecular mechanisms requires further investigation using AD mouse models. In this present work, we subjected amyloid precursor protein (APP)/PS1 mice to a 12-week aerobic treadmill exercise to investigate AHN and its potential mechanisms. We divided 3-month-old littermates wild-type and APP/PS1 transgenic male mice into four groups, and the exercise groups performed 12-week treadmill exercise. Next, we evaluated the influence of treadmill exercise on learning and memory capacity, AHN, and APP proteolytic pathway-related factors. As per our results, the treadmill exercise was able to improve the hippocampal microenvironment in APP/PS1 mice probably by regulating various neurotrophic factors and secretases resulting in APP cleavage through a non-amyloidogenic pathway, which seems to further promote new cell proliferation, survival, and differentiation, enhancing hippocampal neurogenesis. All of these effects ameliorate learning and memory capacity. This study provides a theoretical and experimental basis for understanding AHN in an AD mouse model, which is beneficial for preventing and treating AD.

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