Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Affects Neurogenesis in Mouse Brain

Yongchao Wang; Wen Wen; Hui Li; Hong Xu; Mei Xu; Murong Ma; Jia Luo

doi:10.1016/j.brainresbull.2022.02.019

Back

Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Affects Neurogenesis in Mouse Brain

Journal article

Open access

Peer reviewed

Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Affects Neurogenesis in Mouse Brain

Yongchao Wang, Wen Wen, Hui Li, Hong Xu, Mei Xu, Murong Ma and Jia Luo

Brain research bulletin, Vol.183, pp.49-56

02/25/2022

DOI: 10.1016/j.brainresbull.2022.02.019

PMCID: PMC10014018

PMID: 35227768

Files and links (1)

url

https://doi.org/10.1016/j.brainresbull.2022.02.019View

Published (Version of record) Open Access

Abstract

The mechanisms underlying the regulation of neurogenesis in the adult brain remain unclear. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that has been implicated in various neuropathological processes and endoplasmic reticulum stress. However, the role of MANF in neurogenesis has not been investigated. Using a central nervous system (CNS)-specific Manf knock-out mouse model, we examined the role of MANF in mouse neurogenesis. We demonstrated that MANF deficiency increased BrdU labeling and Ki-67 positive cells in the subgranular zone and subventricular zone. MANF knock-out-induced upregulation of proliferative activity was accompanied by a decrease of cell cycle inhibitors (p15 and p27), an increase of G2/M marker (phospho-histone H3), as well as an increase of neural progenitor markers (Sox2 and NeuroD1) in the brain. In vitro studies using N2A neuroblastoma cells showed that the gain-of-function of MANF inhibited cell cycle progression, whereas the loss-of-function of MANF promoted cell cycle progression. Collectively, our findings indicate MANF deficiency affects cell proliferation and suggest a role of MANF in the neurogenesis of the adult brain.

Cell Cycle

subventricular zone

development

differentiation

neural stem cells

subgranular zone

Details

Title: Subtitle: Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Affects Neurogenesis in Mouse Brain
Creators: Yongchao Wang - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37372
Wen Wen - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Hui Li - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Hong Xu - Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536
Mei Xu - Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536
Murong Ma - Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536
Jia Luo - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Iowa City VA Health Care System, Iowa City, IA 52246. Electronic address: jia-luo@uiowa.edu
Resource Type: Journal article
Publication Details: Brain research bulletin, Vol.183, pp.49-56
DOI: 10.1016/j.brainresbull.2022.02.019
PMID: 35227768
PMCID: PMC10014018
NLM abbreviation: Brain Res Bull
eISSN: 1873-2747
Grant note: DOI: 10.13039/100000027, name: NIAAA, award: AA015407, AA017226, AA026344; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: BX001721; DOI: 10.13039/100006379, name: Office of Research and Development; DOI: 10.13039/100007217, name: Health Services Research and Development; DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 02/25/2022
Academic Unit: Pathology
Record Identifier: 9984222739902771

Metrics

7 Record Views

7 Times Cited - Web of Science