Skip to main content

Advertisement

SpringerLink
Log in

Aging Modulates the Ability of Quiescent Radial Glia-Like Stem Cells in the Hippocampal Dentate Gyrus to be Recruited into Division by Pro-neurogenic Stimuli

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

A delicate balance between quiescence and division of the radial glia-like stem cells (RGLs) ensures continuation of adult hippocampal neurogenesis (AHN) over the lifespan. Transient or persistent perturbations of this balance due to a brain pathology, drug administration, or therapy can lead to unfavorable long-term outcomes such as premature depletion of the RGLs, decreased AHN, and cognitive deficit. Memantine, a drug used for alleviating the symptoms of Alzheimer’s disease, and electroconvulsive seizure (ECS), a procedure used for treating drug-resistant major depression or bipolar disorder, are known strong AHN inducers; they were earlier demonstrated to increase numbers of dividing RGLs. Here, we demonstrated that 1-month stimulation of quiescent RGLs by either memantine or ECS leads to premature exhaustion of their pool and altered AHN at later stages of life and that aging of the brain modulates the ability of the quiescent RGLs to be recruited into the cell cycle by these AHN inducers. Our findings support the aging-related divergence of functional features of quiescent RGLs and have a number of implications for the practical assessment of drugs and treatments with respect to their action on quiescent RGLs at different stages of life in animal preclinical studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All quantitative data are contained within the article. Original microscopy image data sets reported in this paper will be shared by the corresponding author, Dr. Oleg Podgorny (olegpodgorny@inbox.ru), upon request.

References

  1. Altman J (1962) Are new neurons formed in the brains of adult mammals? Science 135:1127–1128. https://doi.org/10.1126/science.135.3509.1127

    Article  CAS  PubMed  Google Scholar 

  2. Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56:337–344. https://doi.org/10.1016/0306-4522(93)90335-D

    Article  CAS  PubMed  Google Scholar 

  3. Gould E, Reeves AJ, Fallah M, et al (1999) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 96:5263–5267. https://doi.org/10.1073/pnas.96.9.5263

  4. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. van Praag H, Schinder AF, Christie BR et al (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034. https://doi.org/10.1038/4151030a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Anacker C, Luna VM, Stevens GS et al (2018) Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 559:98–102. https://doi.org/10.1038/s41586-018-0262-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Berdugo-Vega G, Arias-Gil G, López-Fernández A et al (2020) Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life. Nat Commun 11:135. https://doi.org/10.1038/s41467-019-14026-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Forte N, Boccella S, Tunisi L et al (2021) Orexin-A and endocannabinoids are involved in obesity-associated alteration of hippocampal neurogenesis, plasticity, and episodic memory in mice. Nat Commun 12:6137. https://doi.org/10.1038/s41467-021-26388-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Garthe A, Roeder I, Kempermann G (2016) Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis. Hippocampus 26:261–271. https://doi.org/10.1002/hipo.22520

    Article  PubMed  Google Scholar 

  10. Saxe MD, Battaglia F, Wang J-W, et al (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA 103:17501–17506.https://doi.org/10.1073/pnas.0607207103

  11. Tunc-Ozcan E, Peng C-Y, Zhu Y et al (2019) Activating newborn neurons suppresses depression and anxiety-like behaviors. Nat Commun 10:3768. https://doi.org/10.1038/s41467-019-11641-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anderson ML, Sisti HM, Curlik DM, Shors TJ (2011) Associative learning increases adult neurogenesis during a critical period. Eur J Neurosci 33:175–181. https://doi.org/10.1111/j.1460-9568.2010.07486.x

    Article  PubMed  Google Scholar 

  13. Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61:203–209. https://doi.org/10.1016/0306-4522(94)90224-0

    Article  CAS  PubMed  Google Scholar 

  14. Gould E, McEwen BS, Tanapat P et al (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498. https://doi.org/10.1523/JNEUROSCI.17-07-02492.1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gould E, Beylin A, Tanapat P et al (1999) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260–265. https://doi.org/10.1038/6365

    Article  CAS  PubMed  Google Scholar 

  16. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96:13427–13431.https://doi.org/10.1073/pnas.96.23.13427

  17. Toda T, Parylak SL, Linker SB, Gage FH (2019) The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry 24:67–87. https://doi.org/10.1038/s41380-018-0036-2

    Article  CAS  PubMed  Google Scholar 

  18. Terreros-Roncal J, Moreno-Jiménez EP, Flor-García M et al (2021) Impact of neurodegenerative diseases on human adult hippocampal neurogenesis. Science 374:1106–1113. https://doi.org/10.1126/science.abl5163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moreno-Jiménez EP, Terreros-Roncal J, Flor-García M et al (2021) Evidences for adult hippocampal neurogenesis in humans. J Neurosci 41:2541–2553. https://doi.org/10.1523/JNEUROSCI.0675-20.2020

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sorrells SF, Paredes MF, Zhang Z et al (2021) Positive controls in adults and children support that very few, if any, new neurons are born in the adult human hippocampus. J Neurosci 41:2554–2565. https://doi.org/10.1523/JNEUROSCI.0676-20.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bonaguidi MA, Wheeler MA, Shapiro JS et al (2011) In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145:1142–1155. https://doi.org/10.1016/j.cell.2011.05.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Encinas JM, Michurina TV, Peunova N et al (2011) Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8:566–579. https://doi.org/10.1016/j.stem.2011.03.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mignone JL, Kukekov V, Chiang A-S et al (2004) Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 469:311–324. https://doi.org/10.1002/cne.10964

    Article  CAS  PubMed  Google Scholar 

  24. Seri B, Garcı́a-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160. https://doi.org/10.1523/JNEUROSCI.21-18-07153.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Andersen J, Urbán N, Achimastou A et al (2014) A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells. Neuron 83:1085–1097. https://doi.org/10.1016/j.neuron.2014.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Knobloch M, Pilz G-A, Ghesquière B et al (2017) A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell activity. Cell Rep 20:2144–2155. https://doi.org/10.1016/j.celrep.2017.08.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Morales AV, Mira H (2019) Adult neural stem cells: born to last. Front Cell Dev Biol 7:96. https://doi.org/10.3389/fcell.2019.00096

    Article  PubMed  PubMed Central  Google Scholar 

  28. Urbán N, van den Berg DLC, Forget A et al (2016) Return to quiescence of mouse neural stem cells by degradation of a proactivation protein. Science 353:292–295. https://doi.org/10.1126/science.aaf4802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhou Y, Bond AM, Shade JE et al (2018) Autocrine Mfge8 signaling prevents developmental exhaustion of the adult neural stem cell pool. Cell Stem Cell 23:444-452.e4. https://doi.org/10.1016/j.stem.2018.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sierra A, Encinas JM, Deudero JJP et al (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7:483–495. https://doi.org/10.1016/j.stem.2010.08.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lazutkin A, Podgorny O, Enikolopov G (2019) Modes of division and differentiation of neural stem cells. Behav Brain Res 374:112118. https://doi.org/10.1016/j.bbr.2019.112118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Martín-Suárez S, Valero J, Muro-García T, Encinas JM (2019) Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus. Aging Cell 18:e12958. https://doi.org/10.1111/acel.12958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pilz G-A, Bottes S, Betizeau M et al (2018) Live imaging of neurogenesis in the adult mouse hippocampus. Science 359:658–662. https://doi.org/10.1126/science.aao5056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jang M-H, Bonaguidi MA, Kitabatake Y et al (2013) Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12:215–223. https://doi.org/10.1016/j.stem.2012.11.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kang W, Hebert JM (2015) FGF signaling is necessary for neurogenesis in young mice and sufficient to reverse its decline in old mice. J Neurosci 35:10217–10223. https://doi.org/10.1523/JNEUROSCI.1469-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bao H, Asrican B, Li W et al (2017) Long-range GABAergic inputs regulate neural stem cell quiescence and control adult hippocampal neurogenesis. Cell Stem Cell 21:604-617.e5. https://doi.org/10.1016/j.stem.2017.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yeh C-Y, Asrican B, Moss J et al (2018) Mossy cells control adult neural stem cell quiescence and maintenance through a dynamic balance between direct and indirect pathways. Neuron 99:493-510.e4. https://doi.org/10.1016/j.neuron.2018.07.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Groves N, O’Keeffe I, Lee W et al (2019) Blockade of TrkB but not p75 NTR activates a subpopulation of quiescent neural precursor cells and enhances neurogenesis in the adult mouse hippocampus. Develop Neurobiol 79:868–879. https://doi.org/10.1002/dneu.22729

    Article  CAS  Google Scholar 

  39. Kalamakis G, Brüne D, Ravichandran S et al (2019) Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain. Cell 176:1407-1419.e14. https://doi.org/10.1016/j.cell.2019.01.040

    Article  CAS  PubMed  Google Scholar 

  40. Adusumilli VS, Walker TL, Overall RW et al (2021) ROS dynamics delineate functional states of hippocampal neural stem cells and link to their activity-dependent exit from quiescence. Cell Stem Cell 28:300-314.e6. https://doi.org/10.1016/j.stem.2020.10.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Petrelli F, Scandella V, Montessuit S et al (2023) Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells. Sci Adv 9:eadd5220. https://doi.org/10.1126/sciadv.add5220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bottes S, Jaeger BN, Pilz G-A et al (2021) Long-term self-renewing stem cells in the adult mouse hippocampus identified by intravital imaging. Nat Neurosci 24:225–233. https://doi.org/10.1038/s41593-020-00759-4

    Article  CAS  PubMed  Google Scholar 

  43. Harris L, Rigo P, Stiehl T et al (2021) Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population. Cell Stem Cell 28:863-876.e6. https://doi.org/10.1016/j.stem.2021.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ibrayeva A, Bay M, Pu E et al (2021) Early stem cell aging in the mature brain. Cell Stem Cell 28:955-966.e7. https://doi.org/10.1016/j.stem.2021.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Segi-Nishida E, Warner-Schmidt JL, Duman RS (2008) Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. Proc Natl Acad Sci U S A 105:11352–11357. https://doi.org/10.1073/pnas.0710858105

    Article  PubMed  PubMed Central  Google Scholar 

  46. Namba T, Maekawa M, Yuasa S et al (2009) The Alzheimer’s disease drug memantine increases the number of radial glia-like progenitor cells in adult hippocampus. Glia 57:1082–1090. https://doi.org/10.1002/glia.20831

    Article  PubMed  Google Scholar 

  47. Itaman S, Enikolopov G, Podgorny OV (2022) Detection of de novo dividing stem cells in situ through double nucleotide analogue labeling. Cells 11:4001. https://doi.org/10.3390/cells11244001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mandyam CD, Harburg GC, Eisch AJ (2007) Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse subgranular zone. Neuroscience 146:108–122. https://doi.org/10.1016/j.neuroscience.2006.12.064

    Article  CAS  PubMed  Google Scholar 

  49. Encinas JM, Enikolopov G (2008) Identifying and quantitating neural stem and progenitor cells in the adult brain. In: Methods in Cell Biology. Elsevier, pp 243–272

  50. Maltsev DI, Mellanson KA, Belousov VV et al (2022) The bioavailability time of commonly used thymidine analogues after intraperitoneal delivery in mice: labeling kinetics in vivo and clearance from blood serum. Histochem Cell Biol 157:239–250. https://doi.org/10.1007/s00418-021-02048-y

    Article  CAS  PubMed  Google Scholar 

  51. Podgorny O, Peunova N, Park J-H, Enikolopov G (2018) Triple S-phase labeling of dividing stem cells. Stem Cell Reports 10:615–626. https://doi.org/10.1016/j.stemcr.2017.12.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Maekawa M, Namba T, Suzuki E et al (2009) NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus. Neurosci Res 63:259–266. https://doi.org/10.1016/j.neures.2008.12.006

    Article  CAS  PubMed  Google Scholar 

  53. Kronenberg G, Reuter K, Steiner B et al (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463. https://doi.org/10.1002/cne.10945

    Article  PubMed  Google Scholar 

  54. Seri B, García-Verdugo JM, Collado-Morente L et al (2004) Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus: organization of the Vertebrate Dentate Gyrus. J Comp Neurol 478:359–378. https://doi.org/10.1002/cne.20288

    Article  PubMed  Google Scholar 

  55. Moss J, Gebara E, Bushong EA, et al (2016) Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature. Proc Natl AcadSci USA 113. https://doi.org/10.1073/pnas.1514652113

  56. Brandt MD, Hübner M, Storch A (2012) Brief report: adult hippocampal precursor cells shorten S-phase and total cell cycle length during neuronal differentiation. Stem Cells 30:2843–2847. https://doi.org/10.1002/stem.1244

    Article  CAS  PubMed  Google Scholar 

  57. Fischer TJ, Walker TL, Overall RW et al (2014) Acute effects of wheel running on adult hippocampal precursor cells in mice are not caused by changes in cell cycle length or S phase length. Front Neurosci 8:314. https://doi.org/10.3389/fnins.2014.00314

    Article  PubMed  PubMed Central  Google Scholar 

  58. Solius GM, Maltsev DI, Belousov VV, Podgorny OV (2021) Recent advances in nucleotide analogue-based techniques for tracking dividing stem cells: an overview. J Biol Chem 297:101345. https://doi.org/10.1016/j.jbc.2021.101345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sun D, Chen J, Bao X et al (2015) Protection of radial glial-like cells in the hippocampus of APP/PS1 mice: a novel mechanism of memantine in the treatment of Alzheimer’s disease. Mol Neurobiol 52:464–477. https://doi.org/10.1007/s12035-014-8875-6

    Article  CAS  PubMed  Google Scholar 

  60. Sierra A, Martín-Suárez S, Valcárcel-Martín R et al (2015) Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis. Cell Stem Cell 16:488–503. https://doi.org/10.1016/j.stem.2015.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Cameron HA, McKay RD (1999) Restoring production of hippocampal neurons in old age. Nat Neurosci 2:894–897. https://doi.org/10.1038/13197

    Article  CAS  PubMed  Google Scholar 

  62. Montaron MF, Drapeau E, Dupret D et al (2006) Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging 27:645–654. https://doi.org/10.1016/j.neurobiolaging.2005.02.014

    Article  CAS  PubMed  Google Scholar 

  63. Villeda SA, Luo J, Mosher KI et al (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477:90–94. https://doi.org/10.1038/nature10357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fatt MP, Tran LM, Vetere G et al (2022) Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche. Stem Cell Reports 17:259–275. https://doi.org/10.1016/j.stemcr.2021.12.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cole JD, Sarabia Del Castillo J, Gut G et al (2022) Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging. eLife 11:e68000. https://doi.org/10.7554/eLife.68000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Martín-Suárez S, Encinas JM (2021) The future belongs to those who prepare for it today. Cell Stem Cell 28:783–785. https://doi.org/10.1016/j.stem.2021.04.014

    Article  CAS  PubMed  Google Scholar 

  67. Marvanová M, Lakso M, Pirhonen J et al (2001) The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci 18:247–258. https://doi.org/10.1006/mcne.2001.1027

    Article  CAS  PubMed  Google Scholar 

  68. Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice: BDNF, dietary restriction and neurogenesis. J Neurochem 82:1367–1375. https://doi.org/10.1046/j.1471-4159.2002.01085.x

    Article  CAS  PubMed  Google Scholar 

  69. Li Y, Luikart BW, Birnbaum S et al (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412. https://doi.org/10.1016/j.neuron.2008.06.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tapley P, Lamballe F, Barbacid M (1992) K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors. Oncogene 7:371–381

    CAS  PubMed  Google Scholar 

  71. Pinnock SB, Blake AM, Platt NJ, Herbert J (2010) The roles of BDNF, pCREB and Wnt3a in the latent period preceding activation of progenitor cell mitosis in the adult dentate gyrus by fluoxetine. PLoS One 5:e13652. https://doi.org/10.1371/journal.pone.0013652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci U S A 104:4647–4652.https://doi.org/10.1073/pnas.0610282104

  73. Fong TA, Shawver LK, Sun L et al (1999) SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 59:99–106

    CAS  PubMed  Google Scholar 

  74. Ehm O, Göritz C, Covic M et al (2010) RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci 30:13794–13807. https://doi.org/10.1523/JNEUROSCI.1567-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Jonckheere J, Deloulme J-C, Dall’Igna G et al (2018) Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: the essential role of neuronal survival. Brain Stimulation 11:1336–1347. https://doi.org/10.1016/j.brs.2018.08.001

    Article  PubMed  Google Scholar 

  76. Sairanen M, Lucas G, Ernfors P et al (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25:1089–1094. https://doi.org/10.1523/JNEUROSCI.3741-04.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rossi C, Angelucci A, Costantin L et al (2006) Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 24:1850–1856. https://doi.org/10.1111/j.1460-9568.2006.05059.x

    Article  PubMed  Google Scholar 

  78. Ponti G, Obernier K, Guinto C, et al (2013) Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci USA 110:E1045–E1054.https://doi.org/10.1073/pnas.1219563110

  79. Kohlmeier F, Maya-Mendoza A, Jackson DA (2013) EdU induces DNA damage response and cell death in mESC in culture. Chromosome Res 21:87–100. https://doi.org/10.1007/s10577-013-9340-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494. https://doi.org/10.1002/1096-9861(20001002)425:4%3c479::aid-cne2%3e3.0.co;2-3

    Article  CAS  PubMed  Google Scholar 

  81. Sharma RB, Darko C, Zheng X et al (2019) DNA Damage does not cause BrdU labeling of mouse or human β-cells. Diabetes 68:975–987. https://doi.org/10.2337/db18-0761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by the Russian Foundation for Basic Research, grant no. 19–29-04016 (to O.V.P.); the Ministry of Science and Higher Education of the Russian Federation, grant no. 075–15-2019–1789 to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine (to O.V.P.); and the state assignment of the Ministry of Science and Higher Education of the Russian Federation for 2021–2023 (V.A.A. and N.V.G.).

Author information

Authors and Affiliations

  1. Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, 117997, Russia

    Dmitry I. Maltsev, Vsevolod V. Belousov & Oleg V. Podgorny

  2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    Dmitry I. Maltsev, Vsevolod V. Belousov & Oleg V. Podgorny

  3. Pirogov Russian National Research Medical University, Moscow, 117997, Russia

    Dmitry I. Maltsev & Vsevolod V. Belousov

  4. Laboratory of Functional Biochemistry of Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 117485, Russia

    Victor A. Aniol & Natalia V. Gulyaeva

  5. Lomonosov Moscow State University, Moscow, 119991, Russia

    Mariia A. Golden & Anastasia D. Petrina

  6. Life Improvement By Future Technologies (LIFT) Center, Skolkovo, Moscow, 143025, Russia

    Vsevolod V. Belousov

  7. Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, Moscow, 115419, Russia

    Natalia V. Gulyaeva

  8. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, 117997, Russia

    Oleg V. Podgorny

  9. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia

    Oleg V. Podgorny

Authors
  1. Dmitry I. Maltsev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victor A. Aniol
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariia A. Golden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anastasia D. Petrina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vsevolod V. Belousov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natalia V. Gulyaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Oleg V. Podgorny
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

V.V.B., N.V.G., and O.V.P. designed the experiments. D.I.M., V.A.A., M.A.G., and A.D.P. performed and analyzed the experiments. N.V.G., and O.V.P. interpreted the results and wrote the manuscript. V.V.B. edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Oleg V. Podgorny.

Ethics declarations

Ethics Approval

All manipulations with animals were conducted according to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (1986, ETS 123) and approved by the Institutional Animal Care and Use Committee of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (approval no. 281).

Consent to Participate

Not applicable.

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.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1. Online Resource 1 A cell of the EdU+BrdU-GFP+GFAP+process+ phenotype (a de novo dividing bona fide RGL stem cell). The video illustrates a Z-series of consecutive optical slices obtained using the confocal microscope. The arrow shows the body of an EdU+BrdU- RGL stem cell. The arrowheads show a GFP+GFAP+ apical process of the RGL stem cell (AVI 4530 KB)

Supplementary file2. Online Resource 2 A cell of the EdU+BrdU-GFP+GFAP+process- phenotype (a de novo dividing presumptive RGL stem cell). The video illustrates a Z-series of consecutive optical slices obtained using the confocal microscope. The arrow shows the body of an EdU+BrdU- presumptive RGL stem cell (AVI 1095 KB)

Supplementary file3. Online Resource 3 A cell of the EdU+BrdU-GFP+GFAP-process- phenotype. The video illustrates a Z-series of consecutive optical slices obtained using the confocal microscope. The arrow shows the body of an EdU+BrdU-GFP+GFAP-process- cell (AVI 731 KB)

Supplementary file4. Online Resource 4 Two cells of the EdU+BrdU-GFP-GFAP-process- phenotype. The video illustrates a Z-series of consecutive optical slices obtained using the confocal microscope. The arrows show bodies of two EdU+BrdU-GFP-GFAP-process- cell (AVI 3454 KB)

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.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maltsev, D.I., Aniol, V.A., Golden, M.A. et al. Aging Modulates the Ability of Quiescent Radial Glia-Like Stem Cells in the Hippocampal Dentate Gyrus to be Recruited into Division by Pro-neurogenic Stimuli. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03746-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-023-03746-5

Keywords

Search

Navigation