Stimulation of the muscarinic receptor M4 regulates neural precursor cell proliferation and promotes adult hippocampal neurogenesis
© 2024. Published by The Company of Biologists Ltd..
Cholinergic signaling plays a crucial role in the regulation of adult hippocampal neurogenesis; however, the mechanisms by which acetylcholine mediates neurogenic effects are not completely understood. Here, we report the expression of muscarinic acetylcholine receptor subtype M4 (M4 mAChR) on a subpopulation of neural precursor cells (NPCs) in the adult mouse hippocampus, and demonstrate that its pharmacological stimulation promotes their proliferation, thereby enhancing the production of new neurons in vivo. Using a targeted ablation approach, we also show that medial septum (MS) and the diagonal band of Broca (DBB) cholinergic neurons support both the survival and morphological maturation of adult-born neurons in the mouse hippocampus. Although the systemic administration of an M4-selective allosteric potentiator fails to fully rescue the MS/DBB cholinergic lesion-induced decrease in hippocampal neurogenesis, it further exacerbates the impairment in the morphological maturation of adult-born neurons. Collectively, these findings reveal stage-specific roles of M4 mAChRs in regulating adult hippocampal neurogenesis, uncoupling their positive role in enhancing the production of new neurons from the M4-induced inhibition of their morphological maturation, at least in the context of cholinergic signaling dysfunction.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:151 |
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| Enthalten in: |
Development (Cambridge, England) - 151(2024), 1 vom: 01. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Madrid, Lidia I [VerfasserIn] |
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| Links: |
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| Themen: |
Acetylcholine |
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| Anmerkungen: |
Date Completed 03.01.2024 Date Revised 29.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1242/dev.201835 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a © 2024. Published by The Company of Biologists Ltd. | ||
| 520 | |a Cholinergic signaling plays a crucial role in the regulation of adult hippocampal neurogenesis; however, the mechanisms by which acetylcholine mediates neurogenic effects are not completely understood. Here, we report the expression of muscarinic acetylcholine receptor subtype M4 (M4 mAChR) on a subpopulation of neural precursor cells (NPCs) in the adult mouse hippocampus, and demonstrate that its pharmacological stimulation promotes their proliferation, thereby enhancing the production of new neurons in vivo. Using a targeted ablation approach, we also show that medial septum (MS) and the diagonal band of Broca (DBB) cholinergic neurons support both the survival and morphological maturation of adult-born neurons in the mouse hippocampus. Although the systemic administration of an M4-selective allosteric potentiator fails to fully rescue the MS/DBB cholinergic lesion-induced decrease in hippocampal neurogenesis, it further exacerbates the impairment in the morphological maturation of adult-born neurons. Collectively, these findings reveal stage-specific roles of M4 mAChRs in regulating adult hippocampal neurogenesis, uncoupling their positive role in enhancing the production of new neurons from the M4-induced inhibition of their morphological maturation, at least in the context of cholinergic signaling dysfunction | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acetylcholine | |
| 650 | 4 | |a Adult neurogenesis | |
| 650 | 4 | |a Cholinergic receptors | |
| 650 | 4 | |a Hippocampus | |
| 650 | 4 | |a Medial septum | |
| 650 | 4 | |a Neural precursor cells | |
| 650 | 7 | |a Receptor, Muscarinic M4 |2 NLM | |
| 650 | 7 | |a Cholinergic Agents |2 NLM | |
| 700 | 1 | |a Hafey, Katelyn |e verfasserin |4 aut | |
| 700 | 1 | |a Bandhavkar, Saurabh |e verfasserin |4 aut | |
| 700 | 1 | |a Bodea, Gabriela O |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez-Martin, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Milne, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Tara L |e verfasserin |4 aut | |
| 700 | 1 | |a Faulkner, Geoffrey J |e verfasserin |4 aut | |
| 700 | 1 | |a Coulson, Elizabeth J |e verfasserin |4 aut | |
| 700 | 1 | |a Jhaveri, Dhanisha J |e verfasserin |4 aut | |
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