Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa)
Abstract The 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 cannabin...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-01-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-04600-1 |
| _version_ | 1819007221433892864 |
|---|---|
| author | Lena-Louise Schuele Britta Schuermann Andras Bilkei-Gorzo Sara Gorgzadeh Andreas Zimmer Este Leidmaa |
| author_facet | Lena-Louise Schuele Britta Schuermann Andras Bilkei-Gorzo Sara Gorgzadeh Andreas Zimmer Este Leidmaa |
| author_sort | Lena-Louise Schuele |
| collection | DOAJ |
| description | Abstract The 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. |
| first_indexed | 2024-12-21T00:21:08Z |
| format | Article |
| id | doaj.art-00785b4c972240a1ad3a3a25127f813c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T00:21:08Z |
| publishDate | 2022-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-00785b4c972240a1ad3a3a25127f813c2022-12-21T19:22:06ZengNature PortfolioScientific Reports2045-23222022-01-0112111210.1038/s41598-021-04600-1Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa)Lena-Louise Schuele0Britta Schuermann1Andras Bilkei-Gorzo2Sara Gorgzadeh3Andreas Zimmer4Este Leidmaa5Institute of Molecular Psychiatry, Medical Faculty, University of BonnInstitute of Molecular Psychiatry, Medical Faculty, University of BonnInstitute of Molecular Psychiatry, Medical Faculty, University of BonnInstitute of Molecular Psychiatry, Medical Faculty, University of BonnInstitute of Molecular Psychiatry, Medical Faculty, University of BonnInstitute of Molecular Psychiatry, Medical Faculty, University of BonnAbstract The 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.https://doi.org/10.1038/s41598-021-04600-1 |
| spellingShingle | Lena-Louise Schuele Britta Schuermann Andras Bilkei-Gorzo Sara Gorgzadeh Andreas Zimmer Este Leidmaa Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) Scientific Reports |
| title | Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) |
| title_full | Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) |
| title_fullStr | Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) |
| title_full_unstemmed | Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) |
| title_short | Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa) |
| title_sort | regulation of adult neurogenesis by the endocannabinoid producing enzyme diacylglycerol lipase alpha dagla |
| url | https://doi.org/10.1038/s41598-021-04600-1 |
| work_keys_str_mv | AT lenalouiseschuele regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla AT brittaschuermann regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla AT andrasbilkeigorzo regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla AT saragorgzadeh regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla AT andreaszimmer regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla AT esteleidmaa regulationofadultneurogenesisbytheendocannabinoidproducingenzymediacylglycerollipasealphadagla |