Skip to main content

Advertisement

SpringerLink
Log in

Role of Neuroinflammation in the Establishment of the Neurogenic Microenvironment in Brain Diseases

  • Neurogenic Niche (A Salmina, Section Editor)
  • Published:
Current Tissue Microenvironment Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In many neurological disorders, neuroinflammation contributes not only to the neuropathogenic process but also regulates hippocampal neurogenesis, which plays a critical role in cognitive and emotional functions. A major challenge is to understand how inflammation establishes the neurogenic niche microenvironment to affect the behavior of neural stem cells (NSCs) and/or neural progenitor cells (NPCs). The present review discusses recent advances of research that address such a critical question.

Recent Findings

During the past few years, several human postmortem studies have demonstrated that adult neurogenesis declines significantly during aging and neurological disorders, and that infiltration/activation of T cells and activation of microglia in the neurogenic niche may play a critical role in such decline.

Summary

Neuroinflammation is believed to play a detrimental role in neurodegenerative and regenerative processes. However, the effect of neuroinflammation on neurogenesis appears to be complex, since it depends not only on the various components of inflammatory responses (immune cells and cytokines) present in the microenvironment of neurogenic niches but also on the physiological and differentiation status of NSCs.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 2004;7(2):136–44. https://doi.org/10.1038/nn1172.

    Article  CAS  PubMed  Google Scholar 

  2. Martinez-Cerdeno V, Noctor SC. Neural progenitor cell terminology. Front Neuroanat. 2018;12:104. https://doi.org/10.3389/fnana.2018.00104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. De Juan RC, Borrell V. Coevolution of radial glial cells and the cerebral cortex. Glia. 2015;63(8):1303–19. https://doi.org/10.1002/glia.22827.

    Article  Google Scholar 

  4. Agirman G, Broix L, Nguyen L. Cerebral cortex development: an outside-in perspective. FEBS Lett. 2017;591(24):3978–92. https://doi.org/10.1002/1873-3468.12924.

    Article  CAS  PubMed  Google Scholar 

  5. Altman J. Are new neurons formed in the brains of adult mammals? Science. 1962;135(3509):1127–8. https://doi.org/10.1126/science.135.3509.1127.

    Article  CAS  PubMed  Google Scholar 

  6. Kornack DR, Rakic P. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A. 1999;96(10):5768–73. https://doi.org/10.1073/pnas.96.10.5768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E. Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A. 1999;96(9):5263–7. https://doi.org/10.1073/pnas.96.9.5263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Laplagne DA, Esposito MS, Piatti VC, Morgenstern NA, Zhao C, van Praag H, et al. Functional convergence of neurons generated in the developing and adult hippocampus. PLoS Biol. 2006;4(12):e409. https://doi.org/10.1371/journal.pbio.0040409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Laplagne DA, Kamienkowski JE, Esposito MS, Piatti VC, Zhao C, Gage FH, et al. Similar GABAergic inputs in dentate granule cells born during embryonic and adult neurogenesis. Eur J Neurosci. 2007;25(10):2973–81. https://doi.org/10.1111/j.1460-9568.2007.05549.x.

    Article  PubMed  Google Scholar 

  10. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313–7. https://doi.org/10.1038/3305.

    Article  CAS  PubMed  Google Scholar 

  11. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013;153(6):1219–27. https://doi.org/10.1016/j.cell.2013.05.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. • Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018;555(7696):377–81. https://doi.org/10.1038/nature25975This study revisited the controversy around the scope of human adult neurogenesis. Surprisingly, it reported that neurogenesis dramatically decreases after birth, and only scarce NSCs were found in the old age. Although the results are in contradiction with the consensus that adult neurogenesis is essential for certain forms of memory in humans, the study was carefully carried out, with stringent experimental conditions and an adequate set of control subjects of different ages (including fetal brain).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. • Moreno-Jimenez EP, Flor-Garcia M, Terreros-Roncal J, Rabano A, Cafini F, Pallas-Bazarra N, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25(4):554–60. https://doi.org/10.1038/s41591-019-0375-9This is another well-designed study investigating adult human neurogenesis. The study uses immunohistochemistry to examine various factors known to affect the expression of neurogenic markers. In contrast to Sorrells et al.’s report, the authors found abundant NSCs in the old healthy human brain even at the 9th decade of life, whereas neurogenesis drops sharply in AD patients.

    Article  CAS  PubMed  Google Scholar 

  14. •• Tobin MK, Musaraca K, Disouky A, Shetti A, Bheri A, Honer WG, et al. Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell. 2019;24(6):974–82 e3. https://doi.org/10.1016/j.stem.2019.05.003This is a third paper published in 2019 investigating adult neurogenesis in the human brain. Consistent with Moreno-Jimenez et al.’s findings, this study reported detection of NSCs in old participants with or without AD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, et al. Adult hippocampal neurogenesis along the dorsoventral axis contributes differentially to environmental enrichment combined with voluntary exercise in alleviating chronic inflammatory pain in mice. J Neurosci. 2017;37(15):4145–57. https://doi.org/10.1523/JNEUROSCI.3333-16.2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999;2(3):266–70. https://doi.org/10.1038/6368.

    Article  PubMed  Google Scholar 

  17. Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, et al. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat Med. 2011;17(5):559–65. https://doi.org/10.1038/nm.2336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhou M, Li W, Huang S, Song J, Kim JY, Tian X, et al. mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons. Neuron. 2013;77(4):647–54. https://doi.org/10.1016/j.neuron.2012.12.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Appleby PA, Kempermann G, Wiskott L. The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input. PLoS Comput Biol. 2011;7(1):e1001063. https://doi.org/10.1371/journal.pcbi.1001063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Abdelrahman SA, Samak MA, Shalaby SM. Fluoxetine pretreatment enhances neurogenic, angiogenic and immunomodulatory effects of MSCs on experimentally induced diabetic neuropathy. Cell Tissue Res. 2018;374(1):83–97. https://doi.org/10.1007/s00441-018-2838-6.

    Article  CAS  PubMed  Google Scholar 

  21. Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011;70(4):687–702. https://doi.org/10.1016/j.neuron.2011.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kokovay E, Goderie S, Wang Y, Lotz S, Lin G, Sun Y, et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell. 2010;7(2):163–73. https://doi.org/10.1016/j.stem.2010.05.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gomez-Gaviro MV, Scott CE, Sesay AK, Matheu A, Booth S, Galichet C, et al. Betacellulin promotes cell proliferation in the neural stem cell niche and stimulates neurogenesis. Proc Natl Acad Sci U S A. 2012;109(4):1317–22. https://doi.org/10.1073/pnas.1016199109.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Codega P, Silva-Vargas V, Paul A, Maldonado-Soto AR, Deleo AM, Pastrana E, et al. Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron. 2014;82(3):545–59. https://doi.org/10.1016/j.neuron.2014.02.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008;3(3):279–88. https://doi.org/10.1016/j.stem.2008.07.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron. 2000;28(3):713–26. https://doi.org/10.1016/s0896-6273(00)00148-3.

    Article  CAS  PubMed  Google Scholar 

  27. Aarum J, Sandberg K, Haeberlein SL, Persson MA. Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A. 2003;100(26):15983–8. https://doi.org/10.1073/pnas.2237050100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP 2nd, et al. Microglia instruct subventricular zone neurogenesis. Glia. 2006;54(8):815–25. https://doi.org/10.1002/glia.20419.

    Article  PubMed  Google Scholar 

  29. Shigemoto-Mogami Y, Hoshikawa K, Goldman JE, Sekino Y, Sato K. Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci. 2014;34(6):2231–43. https://doi.org/10.1523/JNEUROSCI.1619-13.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. • Ribeiro Xavier AL, Kress BT, Goldman SA, Lacerda de Menezes JR, Nedergaard M. A Distinct population of microglia supports adult neurogenesis in the subventricular zone. J Neurosci. 2015;35(34):11848–61. https://doi.org/10.1523/JNEUROSCI.1217-15.2015This study highlights a SVZ-specific population of microglia that support adult neurogenesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Matarredona ER, Talaveron R, Pastor AM. Interactions between neural progenitor cells and microglia in the subventricular zone: physiological implications in the neurogenic niche and after implantation in the injured brain. Front Cell Neurosci. 2018;12:268. https://doi.org/10.3389/fncel.2018.00268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kreisel T, Wolf B, Keshet E, Licht T. Unique role for dentate gyrus microglia in neuroblast survival and in VEGF-induced activation. Glia. 2019;67(4):594–618. https://doi.org/10.1002/glia.23505.

    Article  PubMed  Google Scholar 

  33. •• Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. 2006;9(2):268–75. https://doi.org/10.1038/nn1629This study is among the first to report the essential role of immune cells in modulating neurogenesis in homeostasis.

    Article  CAS  PubMed  Google Scholar 

  34. Solano Fonseca R, Mahesula S, Apple DM, Raghunathan R, Dugan A, Cardona A, et al. Neurogenic niche microglia undergo positional remodeling and progressive activation contributing to age-associated reductions in neurogenesis. Stem Cells Dev. 2016;25(7):542–55. https://doi.org/10.1089/scd.2015.0319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996;16(6):2027–33.

    Article  CAS  Google Scholar 

  36. Kempermann G, Kuhn HG, Gage FH. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci. 1998;18(9):3206–12.

    Article  CAS  Google Scholar 

  37. Leuner B, Kozorovitskiy Y, Gross CG, Gould E. Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci U S A. 2007;104(43):17169–73. https://doi.org/10.1073/pnas.0708228104.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hattiangady B, Shetty AK. Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging. 2008;29(1):129–47. https://doi.org/10.1016/j.neurobiolaging.2006.09.015.

    Article  CAS  PubMed  Google Scholar 

  39. Shetty AK, Hattiangady B, Shetty GA. Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes. Glia. 2005;51(3):173–86. https://doi.org/10.1002/glia.20187.

    Article  PubMed  Google Scholar 

  40. Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F. Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell. 2016;19(5):643–52. https://doi.org/10.1016/j.stem.2016.06.013.

    Article  CAS  PubMed  Google Scholar 

  41. Chadashvili T, Peterson DA. Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain. J Comp Neurol. 2006;498(1):1–15. https://doi.org/10.1002/cne.21009.

    Article  CAS  PubMed  Google Scholar 

  42. Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement. 2016;12(6):719–32. https://doi.org/10.1016/j.jalz.2016.02.010.

    Article  PubMed  Google Scholar 

  43. Thundyil J, Lim KL. DAMPs and neurodegeneration. Ageing Res Rev. 2015;24(Pt A):17–28. https://doi.org/10.1016/j.arr.2014.11.003.

    Article  CAS  PubMed  Google Scholar 

  44. Caggiu E, Arru G, Hosseini S, Niegowska M, Sechi G, Zarbo IR, et al. Inflammation, infectious triggers, and Parkinson’s disease. Front Neurol. 2019;10:122. https://doi.org/10.3389/fneur.2019.00122.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O. Neuroinflammation and psychiatric illness. J Neuroinflammation. 2013;10:43. https://doi.org/10.1186/1742-2094-10-43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mondelli V, Vernon AC, Turkheimer F, Dazzan P, Pariante CM. Brain microglia in psychiatric disorders. Lancet Psychiatry. 2017;4(7):563–72. https://doi.org/10.1016/S2215-0366(17)30101-3.

    Article  PubMed  Google Scholar 

  47. Kim YK, Na KS, Myint AM, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:277–84. https://doi.org/10.1016/j.pnpbp.2015.06.008.

    Article  CAS  PubMed  Google Scholar 

  48. Fan LW, Pang Y. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders. Neural Regen Res. 2017;12(3):366–71. https://doi.org/10.4103/1673-5374.202926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A. 2003;100(23):13632–7. https://doi.org/10.1073/pnas.2234031100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302(5651):1760–5. https://doi.org/10.1126/science.1088417.

    Article  CAS  PubMed  Google Scholar 

  51. Chapman KZ, Ge R, Monni E, Tatarishvili J, Ahlenius H, Arvidsson A, et al. Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke. Neurobiol Dis. 2015;83:1–15. https://doi.org/10.1016/j.nbd.2015.08.013.

    Article  CAS  PubMed  Google Scholar 

  52. Chamaa F, Bitar L, Darwish B, Saade NE, Abou-Kheir W. Intracerebroventricular injections of endotoxin (ET) reduces hippocampal neurogenesis. J Neuroimmunol. 2018;315:58–67. https://doi.org/10.1016/j.jneuroim.2017.12.013.

    Article  CAS  PubMed  Google Scholar 

  53. Darwish B, Chamaa F, Al-Chaer ED, Saade NE, Abou-Kheir W. Intranigral injection of endotoxin suppresses proliferation of hippocampal progenitor cells. Front Neurosci. 2019;13:687. https://doi.org/10.3389/fnins.2019.00687.

    Article  PubMed  PubMed Central  Google Scholar 

  54. • Borsini A, Zunszain PA, Thuret S, Pariante CM. The role of inflammatory cytokines as key modulators of neurogenesis. Trends Neurosci. 2015;38(3):145–57. https://doi.org/10.1016/j.tins.2014.12.006This is a comprehensive review of in vitro studies investigating the influence of inflammatory cytokines on NSC behaviors (proliferation, survival, differentiation, migration, neurogenesis, etc.).

    Article  CAS  PubMed  Google Scholar 

  55. Wang B, Jin K. Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis. 2015;30(2):355–65. https://doi.org/10.1007/s11011-014-9523-6.

    Article  CAS  PubMed  Google Scholar 

  56. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:277–86. https://doi.org/10.1016/j.pnpbp.2012.10.022.

    Article  CAS  PubMed  Google Scholar 

  57. Kohman RA, Rhodes JS. Neurogenesis, inflammation and behavior. Brain Behav Immun. 2013;27(1):22–32. https://doi.org/10.1016/j.bbi.2012.09.003.

    Article  CAS  PubMed  Google Scholar 

  58. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus. 2003;13(7):826–34. https://doi.org/10.1002/hipo.10135.

    Article  CAS  PubMed  Google Scholar 

  59. Wu MD, Hein AM, Moravan MJ, Shaftel SS, Olschowka JA, O’Banion MK. Adult murine hippocampal neurogenesis is inhibited by sustained IL-1beta and not rescued by voluntary running. Brain Behav Immun. 2012;26(2):292–300. https://doi.org/10.1016/j.bbi.2011.09.012.

    Article  CAS  PubMed  Google Scholar 

  60. Chen Z, Palmer TD. Differential roles of TNFR1 and TNFR2 signaling in adult hippocampal neurogenesis. Brain Behav Immun. 2013;30:45–53. https://doi.org/10.1016/j.bbi.2013.01.083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Johansson S, Price J, Modo M. Effect of inflammatory cytokines on major histocompatibility complex expression and differentiation of human neural stem/progenitor cells. Stem Cells. 2008;26(9):2444–54. https://doi.org/10.1634/stemcells.2008-0116.

    Article  CAS  PubMed  Google Scholar 

  62. Islam O, Gong X, Rose-John S, Heese K. Interleukin-6 and neural stem cells: more than gliogenesis. Mol Biol Cell. 2009;20(1):188–99. https://doi.org/10.1091/mbc.E08-05-0463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Oh J, McCloskey MA, Blong CC, Bendickson L, Nilsen-Hamilton M, Sakaguchi DS. Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus. J Neurosci Res. 2010;88(13):2798–809. https://doi.org/10.1002/jnr.22447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Vallieres L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci. 2002;22(2):486–92.

    Article  CAS  Google Scholar 

  65. Storer MA, Gallagher D, Fatt MP, Simonetta JV, Kaplan DR, Miller FD. Interleukin-6 regulates adult neural stem cell numbers during normal and abnormal post-natal development. Stem Cell Reports. 2018;10(5):1464–80. https://doi.org/10.1016/j.stemcr.2018.03.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Li Z, Li K, Zhu L, Kan Q, Yan Y, Kumar P, et al. Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation. BMC Immunol. 2013;14:20. https://doi.org/10.1186/1471-2172-14-20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Liu Q, Xin W, He P, Turner D, Yin J, Gan Y, et al. Interleukin-17 inhibits adult hippocampal neurogenesis. Sci Rep. 2014;4:7554. https://doi.org/10.1038/srep07554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cui L, Xue R, Zhang X, Chen S, Wan Y, Wu W. Sleep deprivation inhibits proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK. Brain Res. 2019;1714:81–7. https://doi.org/10.1016/j.brainres.2019.01.024.

    Article  CAS  PubMed  Google Scholar 

  69. Lin Y, Zhang JC, Yao CY, Wu Y, Abdelgawad AF, Yao SL, et al. Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice. Cell Death Dis. 2016;7(6):e2273. https://doi.org/10.1038/cddis.2015.284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Belarbi K, Rosi S. Modulation of adult-born neurons in the inflamed hippocampus. Front Cell Neurosci. 2013;7:145. https://doi.org/10.3389/fncel.2013.00145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, et al. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci. 2006;31(1):149–60. https://doi.org/10.1016/j.mcn.2005.10.006.

    Article  CAS  PubMed  Google Scholar 

  72. Perez-Asensio FJ, Perpina U, Planas AM, Pozas E. Interleukin-10 regulates progenitor differentiation and modulates neurogenesis in adult brain. J Cell Sci. 2013;126(Pt 18):4208–19. https://doi.org/10.1242/jcs.127803.

    Article  CAS  PubMed  Google Scholar 

  73. Pereira L, Font-Nieves M, Van den Haute C, Baekelandt V, Planas AM, Pozas E. IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity. Front Cell Neurosci. 2015;9:57. https://doi.org/10.3389/fncel.2015.00057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Buckwalter MS, Yamane M, Coleman BS, Ormerod BK, Chin JT, Palmer T, et al. Chronically increased transforming growth factor-beta1 strongly inhibits hippocampal neurogenesis in aged mice. Am J Pathol. 2006;169(1):154–64. https://doi.org/10.2353/ajpath.2006.051272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Norton TM, Adams WH, Kollias GV, Clyde VL. Medical and surgical management of benign prostatic hyperplasia, diskospondylitis, and penile paresis in an ocelot. J Am Vet Med Assoc. 1990;197(5):630–2.

    CAS  PubMed  Google Scholar 

  76. Mathieu P, Piantanida AP, Pitossi F. Chronic expression of transforming growth factor-beta enhances adult neurogenesis. Neuroimmunomodulation. 2010;17(3):200–1. https://doi.org/10.1159/000258723.

    Article  CAS  PubMed  Google Scholar 

  77. He Y, Zhang H, Yung A, Villeda SA, Jaeger PA, Olayiwola O, et al. ALK5-dependent TGF-beta signaling is a major determinant of late-stage adult neurogenesis. Nat Neurosci. 2014;17(7):943–52. https://doi.org/10.1038/nn.3732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kandasamy M, Lehner B, Kraus S, Sander PR, Marschallinger J, Rivera FJ, et al. TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons. J Cell Mol Med. 2014;18(7):1444–59. https://doi.org/10.1111/jcmm.12298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. McCusker RH, Kelley KW. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol. 2012;216(Pt 1):84–98. https://doi.org/10.1242/jeb.073411.

    Article  CAS  Google Scholar 

  80. Wolf SA, Steiner B, Akpinarli A, Kammertoens T, Nassenstein C, Braun A, et al. CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J Immunol. 2009;182(7):3979–84. https://doi.org/10.4049/jimmunol.0801218.

    Article  CAS  PubMed  Google Scholar 

  81. Shahaduzzaman M, Golden JE, Green S, Gronda AE, Adrien E, Ahmed A, et al. A single administration of human umbilical cord blood T cells produces long-lasting effects in the aging hippocampus. Age (Dordr). 2013;35(6):2071–87. https://doi.org/10.1007/s11357-012-9496-5.

    Article  CAS  PubMed  Google Scholar 

  82. Sommer A, Winner B, Prots I. The Trojan horse - neuroinflammatory impact of T cells in neurodegenerative diseases. Mol Neurodegener. 2017;12(1):78. https://doi.org/10.1186/s13024-017-0222-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. • Dulken BW, Buckley MT, Navarro Negredo P, Saligrama N, Cayrol R, Leeman DS, et al. Single-cell analysis reveals T cell infiltration in old neurogenic niches. Nature. 2019;571(7764):205–10. https://doi.org/10.1038/s41586-019-1362-5This study revealed a pathogenic role for T cells in reduced neurogenesis during ageing. The authors found that T cells infiltrate the old SVZ and produce IFNγ to affect NSCs. The finding that T cells are clonally expanded in the SVZ suggests the presence of brain-specific antigens (such as misfolding proteins) in old brains.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Garretti F, Agalliu D, Lindestam Arlehamn CS, Sette A, Sulzer D. Autoimmunity in Parkinson’s disease: the role of alpha-synuclein-specific T cells. Front Immunol. 2019;10:303. https://doi.org/10.3389/fimmu.2019.00303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, et al. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia. 2009;57(8):835–49. https://doi.org/10.1002/glia.20810.

    Article  PubMed  Google Scholar 

  86. Gomez-Nicola D, Valle-Argos B, Pallas-Bazarra N, Nieto-Sampedro M. Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells. Mol Biol Cell. 2011;22(12):1960–70. https://doi.org/10.1091/mbc.E11-01-0053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8(9):963–70. https://doi.org/10.1038/nm747.

    Article  CAS  PubMed  Google Scholar 

  88. Lindvall O, Kokaia Z. Neurogenesis following stroke affecting the adult brain. Cold Spring Harb Perspect Biol. 2015;7(11). https://doi.org/10.1101/cshperspect.a019034.

  89. Sun D. Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury. Exp Neurol. 2016;275(Pt 3):405–10. https://doi.org/10.1016/j.expneurol.2015.04.017.

    Article  CAS  PubMed  Google Scholar 

  90. Hoehn BD, Palmer TD, Steinberg GK. Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke. 2005;36(12):2718–24. https://doi.org/10.1161/01.STR.0000190020.30282.cc.

    Article  CAS  PubMed  Google Scholar 

  91. Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, et al. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007;38(1):146–52. https://doi.org/10.1161/01.STR.0000251791.64910.cd.

    Article  CAS  PubMed  Google Scholar 

  92. Bye N, Turnley AM, Morganti-Kossmann MC. Inflammatory regulators of redirected neural migration in the injured brain. Neurosignals. 2012;20(3):132–46. https://doi.org/10.1159/000336542.

    Article  CAS  PubMed  Google Scholar 

  93. Aisen PS. The potential of anti-inflammatory drugs for the treatment of Alzheimer’s disease. Lancet Neurol. 2002;1(5):279–84. https://doi.org/10.1016/s1474-4422(02)00133-3.

    Article  CAS  PubMed  Google Scholar 

  94. Hain EG, Sparenberg M, Rasinska J, Klein C, Akyuz L, Steiner B. Indomethacin promotes survival of new neurons in the adult murine hippocampus accompanied by anti-inflammatory effects following MPTP-induced dopamine depletion. J Neuroinflammation. 2018;15(1):162. https://doi.org/10.1186/s12974-018-1179-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Acosta SA, Diamond DM, Wolfe S, Tajiri N, Shinozuka K, Ishikawa H, et al. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury. PLoS One. 2013;8(12):e81585. https://doi.org/10.1371/journal.pone.0081585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lucassen PJ, Oomen CA, Naninck EF, Fitzsimons CP, van Dam AM, Czeh B, et al. Regulation of adult neurogenesis and plasticity by (early) stress, glucocorticoids, and inflammation. Cold Spring Harb Perspect Biol. 2015;7(9):a021303. https://doi.org/10.1101/cshperspect.a021303.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Lucassen PJ, Meerlo P, Naylor AS, van Dam AM, Dayer AG, Fuchs E, et al. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacology. 2010;20(1):1–17. https://doi.org/10.1016/j.euroneuro.2009.08.003.

    Article  CAS  Google Scholar 

  98. Chesnokova V, Pechnick RN, Wawrowsky K. Chronic peripheral inflammation, hippocampal neurogenesis, and behavior. Brain Behav Immun. 2016;58:1–8. https://doi.org/10.1016/j.bbi.2016.01.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Koo JW, Duman RS. IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A. 2008;105(2):751–6. https://doi.org/10.1073/pnas.0708092105.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry. 2008;13(7):717–28. https://doi.org/10.1038/sj.mp.4002055.

    Article  CAS  PubMed  Google Scholar 

  101. Ben Menachem-Zidon O, Goshen I, Kreisel T, Ben Menahem Y, Reinhartz E, Ben Hur T, et al. Intrahippocampal transplantation of transgenic neural precursor cells overexpressing interleukin-1 receptor antagonist blocks chronic isolation-induced impairment in memory and neurogenesis. Neuropsychopharmacology. 2008;33(9):2251–62. https://doi.org/10.1038/sj.npp.1301606.

    Article  CAS  PubMed  Google Scholar 

  102. Bowen KK, Dempsey RJ, Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport. 2011;22(3):126–30. https://doi.org/10.1097/WNR.0b013e3283430a44.

    Article  CAS  PubMed  Google Scholar 

  103. Vollmayr B, Simonis C, Weber S, Gass P, Henn F. Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry. 2003;54(10):1035–40. https://doi.org/10.1016/s0006-3223(03)00527-4.

    Article  PubMed  Google Scholar 

  104. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301(5634):805–9.

    Article  CAS  Google Scholar 

  105. Malberg JE, Duman RS. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003;28(9):1562–71.

    Article  CAS  Google Scholar 

  106. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature. 2011;476(7361):458–61. https://doi.org/10.1038/nature10287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A. 2010;107(6):2669–74. https://doi.org/10.1073/pnas.0910658107.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Silva AP, Martins T, Baptista S, Goncalves J, Agasse F, Malva JO. Brain injury associated with widely abused amphetamines: neuroinflammation, neurogenesis and blood-brain barrier. Curr Drug Abuse Rev. 2010;3(4):239–54.

    Article  CAS  Google Scholar 

  109. Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Grimmig B, Diamond DM, et al. Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model. PLoS One. 2013;8(1):e53376. https://doi.org/10.1371/journal.pone.0053376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The authors’ work is supported by grants from NIH-NIMH (JJMH), Michael J. Fox Foundation (YP), NIH-MS COBRE/CEPR, and Intramural Research Support Program (YP) of University of Mississippi Medical Center.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Jose Javier Miguel-Hidalgo

  2. Department of Pediatrics, Division of Neonatology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Yi Pang

Authors
  1. Jose Javier Miguel-Hidalgo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Pang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neurogenic Niche

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miguel-Hidalgo, J.J., Pang, Y. Role of Neuroinflammation in the Establishment of the Neurogenic Microenvironment in Brain Diseases. Curr. Tissue Microenviron. Rep. 2, 17–28 (2021). https://doi.org/10.1007/s43152-021-00028-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43152-021-00028-x

Keywords

Search

Navigation