Abstract
Light-based photo-stimulation has demonstrated promising effects on stem cell behavior, particularly in optimizing neurogenesis. However, the precise parameters for achieving optimal results, including the wavelengths, light intensity, radiating energy, and underlying mechanisms, remain incompletely understood. In this study, we focused on utilizing ultraviolet-C (UV-C) at a specific wavelength of 254 nm, with an ultra-low dose at intensity of 330 μW/cm2 and a total energy of 594 mJ/cm2 per day over a period of seven days, to stimulate the proliferation and differentiation of mouse neural stem cells (NSCs). The results revealed that the application of ultra-low-dose UV-C yielded the most significant effect in promoting differentiation when compared to mixed ultraviolet (UV) and ultraviolet-A (UV-A) radiation at equivalent exposure levels. The mechanism exploration elucidated the role of Presenilin 1 in mediating the activation of β-catenin and Notch 1 by the UV-C treatment, both of which are key factors facilitating NSCs proliferation and differentiation. These findings introduce a novel approach employing ultra-low-dose UV-C for specifically enhancing NSC differentiation, as well as the underlying mechanism. It would contribute valuable insights into brain stimulation and neurogenesis modulation for various diseases, offering potential therapeutic avenues for further exploration.
Graphical Abstract
Ultra-low-dose UV-C photo-stimulation promoted the differentiation of neural stem cells (NSCs) through Presenilin 1 mediated β-catenin and Notch 1 activations.
Similar content being viewed by others
Data Availability
No datasets were generated or analysed during the current study.
Abbreviations
- bFGF :
-
Basic fibroblast growth factor
- cDNA :
-
Complementary DNA
- DAPI :
-
4′,6-Diamidino-2-phenylindole
- DMEM/F12 :
-
Dulbecco’s Modified Eagle’s Medium/Nutrient Mixture F-12 Ham
- DNA :
-
Deoxyribonucleic acid
- ECL :
-
Enhanced chemiluminescence
- EGF :
-
Epidermal growth factor
- GAPDH :
-
Glyceraldehyde-3-phosphate dehydrogenase
- GFAP :
-
Glial fibrillary acidic protein
- HES1 :
-
Hairy and enhancer of split-1
- MAP2 :
-
Microtubule-associated protein 2
- MMLV :
-
Moloney Murine Leukemia Virus Reverse Transcriptase
- mRNA :
-
Messenger ribonucleic acid
- ND1 :
-
Differentiation 1, NeuroD1
- NES :
-
Coding gene of Nestin
- NICD :
-
Notch Intracellular Domain
- NSCs :
-
Neural stem cells
- PBS :
-
Phosphate-buffered saline
- PCR :
-
Polymerase chain reaction
- PDL :
-
Poly-D-lysine
- PS1 :
-
Presenilin 1
- PFA :
-
Paraformaldehyde
- UV :
-
Ultraviolet
- UV-A :
-
Ultraviolet-A
- UV-C :
-
Ultraviolet-C
References
de Tommaso M et al (2007) Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine. Clin Neurophysiol 118:2297–2304. https://doi.org/10.1016/j.clinph.2007.06.060
LaLumiere RT (2011) A new technique for controlling the brain: optogenetics and its potential for use in research and the clinic. Brain Stimul 4:1–6. https://doi.org/10.1016/j.brs.2010.09.009
Saadati M, Akhavan O, Fazli H, Nemati S, Baharvand H (2023) Controlled differentiation of human neural progenitor cells on molybdenum disulfide/graphene oxide heterojunction scaffolds by photostimulation. ACS Appl Mater Interfaces 15:3713–3730. https://doi.org/10.1021/acsami.2c15431
Zhang C et al (2019) Optimized photo-stimulation of halorhodopsin for long-term neuronal inhibition. BMC Biol 17:95. https://doi.org/10.1186/s12915-019-0717-6
Shen MH, Singh RK (2022) Effective UV wavelength range for increasing aflatoxins reduction and decreasing oil deterioration in contaminated peanuts. Food Res Int 154:111016. https://doi.org/10.1016/j.foodres.2022.111016
Omur AD (2022) Evaluation of the effects of photostimulation on freeze-thawed bull sperm cells in terms of reproductive potential. Pol J Vet Sci 25:249–259. https://doi.org/10.24425/pjvs.2022.141809
Zhang X, Dorlhiac G, Landry MP, Streets A (2022) Phototoxic effects of nonlinear optical microscopy on cell cycle, oxidative states, and gene expression. Sci Rep 12:18796. https://doi.org/10.1038/s41598-022-23054-7
Roy M, Corti A, Dorocka-Bobkowska B, Pompella A (2022) Positive effects of uv-photofunctionalization of titanium oxide surfaces on the survival and differentiation of osteogenic precursor cells-an in vitro study. J Funct Biomater 13(4):265. https://doi.org/10.3390/jfb13040265
Moon H et al (2017) Melanocyte stem cell activation and translocation initiate cutaneous melanoma in response to UV exposure. Cell Stem Cell 21:665-678 e666. https://doi.org/10.1016/j.stem.2017.09.001
Sandri A, Tessari A, Giannetti D, Cetti A, Lleo MM, Boschi F (2023) UV-A radiation: Safe human exposure and antibacterial activity. Int J Mol Sci 24(9):8331. https://doi.org/10.3390/ijms24098331
Bai Y et al (2022) Flavonoids metabolism and physiological response to ultraviolet treatments in Tetrastigma hemsleyanum Diels et Gilg. Front Plant Sci 13:926197. https://doi.org/10.3389/fpls.2022.926197
Liu Q et al (2023) Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3beta/beta-catenin activation. Cell Biosci 13:4. https://doi.org/10.1186/s13578-023-00954-3
Sigloch V, Spitz D, Driever W (2023) A network of Notch-dependent and -independent her genes controls neural stem and progenitor cells in the zebrafish thalamic proliferation zone. Development (Cambridge, England) 150(7):dev201301. https://doi.org/10.1242/dev.201301
Liu Q et al (2018) GRP78 promotes neural stem cell antiapoptosis and survival in response to oxygen-glucose deprivation (OGD)/reoxygenation through pi3k/akt, erk1/2, and nf-kappab/p65 pathways. Oxid Med Cell Longev 2018:3541807. https://doi.org/10.1155/2018/3541807
Liu Q et al (2016) Inhibition of HSP90 promotes neural stem cell survival from oxidative stress through attenuating NF-kappaB/p65 activation. Oxid Med Cell Longev 2016:3507290. https://doi.org/10.1155/2016/3507290
Liu Q et al (2014) Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation via Notch pathway activation. Neurosci Lett 559:1–6. https://doi.org/10.1016/j.neulet.2013.11.027
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
Bonds JA et al (2015) Presenilin-1 dependent neurogenesis regulates hippocampal learning and memory. PLoS One 10:e0131266. https://doi.org/10.1371/journal.pone.0131266
Veeraraghavalu K, Choi SH, Zhang X, Sisodia SS (2010) Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling. J Neurosci 30:6903–6915. https://doi.org/10.1523/JNEUROSCI.0527-10.2010
Jones DL, Baxter BK (2017) DNA repair and photoprotection: mechanisms of overcoming environmental ultraviolet radiation exposure in halophilic archaea. Front Microbiol 8:1882. https://doi.org/10.3389/fmicb.2017.01882
Fuentes-Leon F et al (2024) Genotoxicity of ultraviolet light and sunlight in the bacterium Caulobacter crescentus: Wavelength-dependence. Mutat Res Genet Toxicol Environ Mutagen 894:503727. https://doi.org/10.1016/j.mrgentox.2024.503727
Patwardhan J, Bhatt P (2016) Flavonoids derived from abelmoschus esculentus attenuates uv-b induced cell damage in human dermal fibroblasts through Nrf2-ARE pathway. Pharmacogn Mag 12:S129-138. https://doi.org/10.4103/0973-1296.182175
Mohania D et al (2017) Ultraviolet radiations: skin defense-damage mechanism. Adv Exp Med Biol 996:71–87. https://doi.org/10.1007/978-3-319-56017-5_7
Jantaro S, Baebprasert W, Piyamawadee C, Sodsuay O, Incharoensakdi A (2014) Exogenous spermidine alleviates UV-induced growth inhibition of Synechocystis sp. PCC 6803 via reduction of hydrogen peroxide and malonaldehyde levels. Appl Biochem Biotechnol 173:1145–1156. https://doi.org/10.1007/s12010-014-0887-1
Bagheri-Mohammadi S (2022) Adult neurogenesis and the molecular signalling pathways in brain: the role of stem cells in adult hippocampal neurogenesis. Int J Neurosci 132:1165–1177. https://doi.org/10.1080/00207454.2020.1865953
Li Q et al (2021) RYBP modulates embryonic neurogenesis involving the Notch signaling pathway in a PRC1-independent pattern. Stem Cell Reports 16:2988–3004. https://doi.org/10.1016/j.stemcr.2021.10.013
Hijroudi F et al (2022) Neural stem cells secretome increased neurogenesis and behavioral performance and the activation of Wnt/beta-catenin signaling pathway in mouse model of alzheimer’s disease. Neuromolecular Med 24:424–436. https://doi.org/10.1007/s12017-022-08708-z
Batista MR et al (2021) Balanced Notch-Wnt signaling interplay is required for mouse embryo and fetal development. Reproduction 161:385–398. https://doi.org/10.1530/REP-20-0435
Jang C et al (2011) Calsenilin regulates presenilin 1/gamma-secretase-mediated N-cadherin epsilon-cleavage and beta-catenin signaling. FASEB J 25:4174–4183. https://doi.org/10.1096/fj.11-185926
Romero AA, Gross SR, Cheng KY, Goldsmith NK, Geller HM (2003) An age-related increase in resistance to DNA damage-induced apoptotic cell death is associated with development of DNA repair mechanisms. J Neurochem 84:1275–1287. https://doi.org/10.1046/j.1471-4159.2003.01629.x
Shirai K et al (2006) Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro. Neurosci Lett 399:57–60. https://doi.org/10.1016/j.neulet.2006.01.048
Semkova V, Haupt S, Segschneider M, Bell C, Ingelman-Sundberg M, Hajo M, Weykopf B, Muthukottiappan P, Till A, Brüstle O (2022) Dynamics of metabolic pathways and stress response patterns during human neural stem cell proliferation and differentiation. Cells 11(9):1388. https://doi.org/10.3390/cells11091388
Kagias K, Nehammer C, Pocock R (2012) Neuronal responses to physiological stress. Front Genet 3:222. https://doi.org/10.3389/fgene.2012.00222
Vecera J et al (2020) Hypoxia/Hif1alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1. Stem Cell Res 45:101770. https://doi.org/10.1016/j.scr.2020.101770
Bejoy J et al (2020) Wnt-Notch signaling interactions during neural and astroglial patterning of human stem cells. Tissue Eng Part A 26:419–431. https://doi.org/10.1089/ten.TEA.2019.0202
Contreras EG, Egger B, Gold KS, Brand AH (2018) Dynamic notch signalling regulates neural stem cell state progression in the drosophila optic lobe. Neural Dev 13:25. https://doi.org/10.1186/s13064-018-0123-8
Pronin S, Koh CH, Hughes M (2017) Effects of ultraviolet radiation on glioma: systematic review. J Cell Biochem 118:4063–4071. https://doi.org/10.1002/jcb.26061
Vasilev A, Sofi R, Rahman R, Smith SJ, Teschemacher AG, Kasparov S (2020) Using Light for Therapy of Glioblastoma Multiforme (GBM). Brain Sci 10(2):75. https://doi.org/10.3390/brainsci10020075
Funding
This study was funded by: Shenzhen International Cooperation Projects GJHZ20210705141404013 and SIAT Innovation Program for Excellent Young Researcher award to Q.L.
Author information
Authors and Affiliations
Contributions
Qian Liu: Conceptualization, Methodology, Investigation, Writing- review and editing, Supervision, Funding acquisition. Lin Zhou: Conceptualization, Methodology, Review and editing, Investigation, Data curation. Zihan Wang: Investigation. Qiuling Zhong: Investigation. Bing Song: Resources. Yan Wang: Resources, Project administration, Writing. Teng Guan: Data curation, Manuscript proof reading. All authors contributed to the study and the manuscript preparation.
Corresponding author
Ethics declarations
Ethics Approval and Consent to Participate
The experiments conducted on animals were approved by the IACUC of Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences Research Ethics Committees. The approved project is: Physical stimulation for ischemic stroke treatment. (Approval number: SIAT-IACUC-210615-YGS-LQ-A19952, Approved Date: 06/18/2021).
Consent for Publication
Not applicable.
Competing Interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhou, L., Wang, Z., Zhong, Q. et al. Ultra-Low-Dose UV-C Photo-stimulation Promotes Neural Stem Cells Differentiation via Presenilin 1 Mediated Notch and β-Catenin Activation. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04185-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12035-024-04185-6