Neuropeptides Modulate Local Astrocytes to Regulate Adult Hippocampal Neural Stem Cells

Brent Asrican; Josh Wooten; Ya-Dong Li; Luis Quintanilla; Feiran Zhang; Connor Wander; Hechen Bao; Chia-Yu Yeh; Yan-Jia Luo; Reid Olsen; Szu-Aun Lim; Jessica Hu; Peng Jin; Juan Song

doi:10.1016/j.neuron.2020.07.039

Neuropeptides Modulate Local Astrocytes to Regulate Adult Hippocampal Neural Stem Cells

Neuron. 2020 Oct 28;108(2):349-366.e6. doi: 10.1016/j.neuron.2020.07.039. Epub 2020 Sep 1.

Authors

Brent Asrican¹, Josh Wooten², Ya-Dong Li¹, Luis Quintanilla³, Feiran Zhang⁴, Connor Wander⁵, Hechen Bao¹, Chia-Yu Yeh¹, Yan-Jia Luo¹, Reid Olsen⁶, Szu-Aun Lim⁶, Jessica Hu⁶, Peng Jin⁴, Juan Song⁷

Affiliations

¹ Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.
⁵ Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Pharmacology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶ Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷ Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: juansong@email.unc.edu.

Abstract

Neural stem cells (NSCs) in the dentate gyrus (DG) reside in a specialized local niche that supports their neurogenic proliferation to produce adult-born neurons throughout life. How local niche cells interact at the circuit level to ensure continuous neurogenesis from NSCs remains unknown. Here we report the role of endogenous neuropeptide cholecystokinin (CCK), released from dentate CCK interneurons, in regulating neurogenic niche cells and NSCs. Specifically, stimulating CCK release supports neurogenic proliferation of NSCs through a dominant astrocyte-mediated glutamatergic signaling cascade. In contrast, reducing dentate CCK induces reactive astrocytes, which correlates with decreased neurogenic proliferation of NSCs and upregulation of genes involved in immune processes. Our findings provide novel circuit-based information on how CCK acts on local astrocytes to regulate the key behavior of adult NSCs.

Keywords: adult neural stem cells; astrocytes; cholecystokinin; hippocampus; neurogenesis; neuroinflammation; neuropeptide.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / physiology*
Cholecystokinin / physiology*
Dentate Gyrus / physiology*
Female
Interneurons / physiology*
Male
Membrane Potentials
Mice, Inbred C57BL
Mice, Transgenic
Neural Stem Cells / physiology*
Neurogenesis*
Neuropeptides / physiology*
Signal Transduction

Substances

Neuropeptides
Cholecystokinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding