Elevated P38MAPK Activity Promotes Neural Stem Cell Aging

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Apr 4

PMID 32243258

Citations 8

Authors

Leire Moreno-Cugnon

Olatz Arrizabalaga

Irantzu Llarena

Ander Matheu

Affiliations

Soon will be listed here.

Abstract

Age-progressive neural stem cell (NSC) dysfunction leads to impaired neurogenesis, cognitive decline and the onset of age-related neurodegenerative pathologies. p38MAPK signalling pathway limits stem cell activity during aging in several tissues. Its role in NSCs remains controversial. In this work, we show that p38MAPK activity increases in NSCs with age in the subventricular zone (SVZ) and its pharmacological inhibition is sufficient to rejuvenate their activity . These data reveal a cell-autonomous role for p38MAPK increase in decreasing NSC homeostasis with age. This information shed light in the role of p38MAPK in NSC aging.

Citing Articles

Glycyrrhizin regulates the HMGB1/P38MAPK signalling pathway in status epilepticus.

Luo Z, Xu M, Zhang L, Zhang H, Xu Z, Xu Z Mol Med Rep. 2023; 27(2).

PMID: 36633134 PMC: 9887508. DOI: 10.3892/mmr.2023.12932.

Multiple Roles of Paeoniflorin in Alzheimer's Disease.

Meng Z, Chen H, Deng C, Meng S Evid Based Complement Alternat Med. 2022; 2022:2464163.

PMID: 35449815 PMC: 9017479. DOI: 10.1155/2022/2464163.

Rejuvenation of Tissue Stem Cells by Intrinsic and Extrinsic Factors.

Cai Y, Wang S, Qu J, Izpisua Belmonte J, Liu G Stem Cells Transl Med. 2022; 11(3):231-238.

PMID: 35303745 PMC: 8968747. DOI: 10.1093/stcltm/szab012.

p38MAPK Signaling Pathway in Osteoarthritis: Pathological and Therapeutic Aspects.

Li Z, Dai A, Yang M, Chen S, Deng Z, Li L J Inflamm Res. 2022; 15:723-734.

PMID: 35140502 PMC: 8820459. DOI: 10.2147/JIR.S348491.

Opportunities and Challenges in Stem Cell Aging.

Larijani B, Foroughi-Heravani N, Alaei S, Rezaei-Tavirani M, Alavi-Moghadam S, Payab M Adv Exp Med Biol. 2021; 1341:143-175.

PMID: 33748933 DOI: 10.1007/5584_2021_624.

References

Bond A, Ming G, Song H . Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later. Cell Stem Cell. 2015; 17(4):385-95. PMC: 4683085. DOI: 10.1016/j.stem.2015.09.003. View

DeCarolis N, Kirby E, Wyss-Coray T, Palmer T . The Role of the Microenvironmental Niche in Declining Stem-Cell Functions Associated with Biological Aging. Cold Spring Harb Perspect Med. 2015; 5(12). PMC: 4665032. DOI: 10.1101/cshperspect.a025874. View

Bernet J, Doles J, Hall J, Kelly Tanaka K, Carter T, Olwin B . p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nat Med. 2014; 20(3):265-71. PMC: 4070883. DOI: 10.1038/nm.3465. View

Cheng A, Chan S, Milhavet O, Wang S, Mattson M . p38 MAP kinase mediates nitric oxide-induced apoptosis of neural progenitor cells. J Biol Chem. 2001; 276(46):43320-7. DOI: 10.1074/jbc.M107698200. View

Hamanoue M, Morioka K, Ohsawa I, Ohsawa K, Kobayashi M, Tsuburaya K . Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells. Sci Rep. 2016; 6:24279. PMC: 4828673. DOI: 10.1038/srep24279. View

Shi Z, Geng Y, Liu J, Zhang H, Zhou L, Lin Q . Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations. Protein Cell. 2017; 9(4):351-364. PMC: 5876182. DOI: 10.1007/s13238-017-0450-2. View

Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S . Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004; 24(38):8354-65. PMC: 6729689. DOI: 10.1523/JNEUROSCI.2751-04.2004. View

Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K . Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006; 12(4):446-51. DOI: 10.1038/nm1388. View

Cosgrove B, Gilbert P, Porpiglia E, Mourkioti F, Lee S, Corbel S . Rejuvenation of the muscle stem cell population restores strength to injured aged muscles. Nat Med. 2014; 20(3):255-64. PMC: 3949152. DOI: 10.1038/nm.3464. View

10.

Ventura J, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M . p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet. 2007; 39(6):750-8. DOI: 10.1038/ng2037. View

11.

Cortez I, Bulavin D, Wu P, McGrath E, Cunningham K, Wakamiya M . Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning. Behav Brain Res. 2016; 322(Pt B):212-222. PMC: 5817636. DOI: 10.1016/j.bbr.2016.10.023. View

12.

Arrizabalaga O, Moreno-Cugnon L, Auzmendi-Iriarte J, Aldaz P, de Caceres I, Garros-Regulez L . High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response. Oncogenesis. 2017; 6(12):401. PMC: 5865544. DOI: 10.1038/s41389-017-0003-9. View

13.

Sherr C, DePinho R . Cellular senescence: mitotic clock or culture shock?. Cell. 2000; 102(4):407-10. DOI: 10.1016/s0092-8674(00)00046-5. View

14.

Yoshioka K, Namiki K, Sudo T, Kasuya Y . p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus. FEBS Open Bio. 2015; 5:437-44. PMC: 4472823. DOI: 10.1016/j.fob.2015.05.001. View

15.

Kase Y, Otsu K, Shimazaki T, Okano H . Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling. Stem Cell Reports. 2019; 12(6):1313-1328. PMC: 6565990. DOI: 10.1016/j.stemcr.2019.04.010. View

16.

Schultz M, Sinclair D . When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development. 2016; 143(1):3-14. PMC: 4725211. DOI: 10.1242/dev.130633. View

17.

Yang S, Kim S, Byun K, Hutchinson B, Lee B, Michikawa M . NPC1 gene deficiency leads to lack of neural stem cell self-renewal and abnormal differentiation through activation of p38 mitogen-activated protein kinase signaling. Stem Cells. 2005; 24(2):292-8. DOI: 10.1634/stemcells.2005-0221. View

18.

Encinas J, Sierra A . Neural stem cell deforestation as the main force driving the age-related decline in adult hippocampal neurogenesis. Behav Brain Res. 2011; 227(2):433-9. DOI: 10.1016/j.bbr.2011.10.010. View

19.

Reynolds B, Weiss S . Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol. 1996; 175(1):1-13. DOI: 10.1006/dbio.1996.0090. View

20.

Colie S, Sarroca S, Palenzuela R, Garcia I, Matheu A, Corpas R . Neuronal p38α mediates synaptic and cognitive dysfunction in an Alzheimer's mouse model by controlling β-amyloid production. Sci Rep. 2017; 7:45306. PMC: 5374488. DOI: 10.1038/srep45306. View