Combined ionizing radiation exposure improves behavioral symptoms and modulates brain innate immune system activity in the Tau P301S mice line

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Abstract

Tauopathies are a group of neurodegenerative diseases associated with abnormal phosphorylation and aggregation of the microtubule-associated tau-protein. Currently, there is no pathogenetic treatment for tauopathies, but the process of neuroinflammation that accompanies the diseases appears to be a promising therapeutic target. According to the literature, ionizing radiation (IR) may be one of the effective tools to manage neuroinflammation. Here, we investigated the effects of combined ionizing radiation (γ-quanta and carbon-12 nuclei) on locomotor abilities and markers of microglia activation in the brain of transgenic Tau P301S mice line reproducing tauopathy. Irradiation led to improvement in behavioral symptoms of the mice: increased endurance (in the early symptomatic stage) and enhanced locomotor activity (in the terminal stage). At the same time, irradiation resulted in increased levels of pro-inflammatory and anti-inflammatory cytokines and chemokines in the cerebellum and, to a lesser extent, in the hippocampus of irradiated mice. The obtained data indicate a significant modulating effect of IR on the innate immune system, and also indicate a high potential of radiotherapy as a therapeutic method for the treatment of neurodegeneration.

About the authors

V. S. Kokhan

“Serbsky National Medical Research Center of Psychiatry and Narcology” Russian Ministry of Health

Email: shamakina.i@serbsky.ru
Russian Federation, 119002 Moscow

R. A. Ageldinov

Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia

Email: shamakina.i@serbsky.ru
Russian Federation, 143442 Moscow Region

P. K. Anokhin

“Serbsky National Medical Research Center of Psychiatry and Narcology” Russian Ministry of Health; Artificial Intelligence Research Institute

Email: shamakina.i@serbsky.ru
Russian Federation, 119002 Moscow; 121170 Moscow

I. Y. Shamakina

“Serbsky National Medical Research Center of Psychiatry and Narcology” Russian Ministry of Health

Author for correspondence.
Email: shamakina.i@serbsky.ru
Russian Federation, 119002 Moscow

References

  1. Koivisto, H., Ytebrouck, E., Carmans, S., Naderi, R., Miettinen, P. O., Roucourt, B., and Tanila, H. (2019) Progressive age-dependent motor impairment in human tau P301S overexpressing mice, Behav. Brain Res., 376, 112158, doi: 10.1016/j.bbr.2019.112158.
  2. Chen, Y., and Yu, Y. (2023) Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation, J. Neuroinflamm., 20, doi: 10.1186/s12974-023-02853-3.
  3. Buccellato, F. R., D'Anca, M., Tartaglia, G. M., Del Fabbro, M., Scarpini, E., and Galimberti, D. (2023) Treatment of Alzheimer's disease: beyond symptomatic therapies, Int. J. Mol. Sci., 24, doi: 10.3390/ijms241813900.
  4. Melchiorri, D., Merlo, S., Micallef, B., Borg, J. J., and Drafi, F. (2023) Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy? Front. Pharmacol., 14, 1196413, doi: 10.3389/fphar.2023.1196413.
  5. Orr, M. E., Sullivan, A. C., and Frost, B. (2017) A brief overview of tauopathy: causes, consequences, and therapeutic strategies, Trends Pharmacol. Sci., 38, 637-648, doi: 10.1016/j.tips.2017.03.011.
  6. Ising, C., and Heneka, M. T. (2023) Chronic inflammation: a potential target in tauopathies, Lancet Neurol., 22, 371-373, doi: 10.1016/s1474-4422(23)00116-3.
  7. Correia, A. S., Cardoso, A., and Vale, N. (2021) Highlighting immune system and stress in major depressive disorder, Parkinson's, and Alzheimer's diseases, with a connection with serotonin, Int. J. Mol. Sci., 22, doi: 10.3390/ijms22168525.
  8. Salani, F., Sterbini, V., Sacchinelli, E., Garramone, M., and Bossu, P. (2019) Is Innate Memory a Double-Edge Sword in Alzheimer's Disease? A Reappraisal of New Concepts and Old Data, Front. Immunol., 10, 1768, doi: 10.3389/fimmu.2019.01768.
  9. Muzio, L., and Perego, J. (2024) CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis, Int. J. Mol. Sci., 25, doi: 10.3390/ijms25094865.
  10. Hoozemans, J. J., Veerhuis, R., Rozemuller, J. M., and Eikelenboom, P. (2006) Neuroinflammation and regeneration in the early stages of Alzheimer's disease pathology, Int. J. Dev. Neurosci., 24, 157-165, doi: 10.1016/j.ijdevneu.2005.11.001.
  11. Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., Herrup, K., Frautschy, S. A., Finsen, B., Brown, G. C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A., Petzold, G. C., et al. (2015) Neuroinflammation in Alzheimer's disease, Lancet Neurol., 14, 388-405, doi: 10.1016/S1474-4422(15)70016-5.
  12. Kempuraj, D., Thangavel, R., Natteru, P. A., Selvakumar, G. P., Saeed, D., Zahoor, H., Zaheer, S., Iyer, S. S., and Zaheer, A. (2016) Neuroinflammation induces neurodegeneration, J. Neurol. Neurosurg. Spine, 1, 1003.
  13. Li, T., Lu, L., Pember, E., Li, X., Zhang, B., and Zhu, Z. (2022) New insights into neuroinflammation involved in pathogenic mechanism of Alzheimer's disease and its potential for therapeutic intervention, Cells, 11, doi: 10.3390/cells11121925.
  14. Jin, X., and Yamashita, T. (2016) Microglia in central nervous system repair after injury, J. Biochem., 159, 491-496, doi: 10.1093/jb/mvw009.
  15. Yoshida, K., and Toya, S. (1997) Neurotrophic activity in cytokine-activated astrocytes, Keio J. Med., 46, 55-60, doi: 10.2302/kjm.46.55.
  16. Chen, Z., and Trapp, B. D. (2015) Microglia and neuroprotection, J. Neurochem., 136, 10-17, doi: 10.1111/jnc.13062.
  17. Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., 3rd, Lafaille, J. J., Hempstead, B. L., Littman, D. R., and Gan, W. B. (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor, Cell, 155, 1596-1609, doi: 10.1016/j.cell.2013.11.030.
  18. Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., Ragozzino, D., and Gross, C. T. (2011) Synaptic Pruning by microglia is necessary for normal brain development, Science, 333, 1456-1458, doi: 10.1126/science.1202529.
  19. Liu, P., Wang, Y., Sun, Y., and Peng, G. (2022) Neuroinflammation as a potential therapeutic target in Alzheimer's disease, Clin. Interv. Aging, 17, 665-674, doi: 10.2147/CIA.S357558.
  20. Boyd, A., Byrne, S., Middleton, R. J., Banati, R. B., and Liu, G. J. (2021) Control of neuroinflammation through radiation-induced microglial changes, Cells, 10, doi: 10.3390/cells10092381.
  21. Kempf, S. J., Janik, D., Barjaktarovic, Z., Braga-Tanaka, I., 3rd, Tanaka, S., Neff, F., Saran, A., Larsen, M. R., and Tapio, S. (2016) Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE–/– Alzheimer's mouse model, Oncotarget, 7, 71817-71832, doi: 10.18632/oncotarget.12376.
  22. Yang, E. J., Kim, H., Choi, Y., Kim, H. J., Kim, J. H., Yoon, J., Seo, Y. S., and Kim, H. S. (2021) Modulation of neuroinflammation by low-dose radiation therapy in an animal model of Alzheimer's disease, Int. J. Radiat. Oncol. Biol. Physics, 111, 658-670, doi: 10.1016/j.ijrobp.2021.06.012.
  23. Marples, B., McGee, M., Callan, S., Bowen, S. E., Thibodeau, B. J., Michael, D. B., Wilson, G. D., Maddens, M. E., Fontanesi, J., and Martinez, A. A. (2016) Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer’s disease (AD), Radiother. Oncol., 118, 43-51, doi: 10.1016/j.radonc.2015.10.019.
  24. Wilson, G. D., Wilson, T. G., Hanna, A., Fontanesi, G., Kulchycki, J., Buelow, K., Pruetz, B. L., Michael, D. B., Chinnaiyan, P., Maddens, M. E., Martinez, A. A., and Fontanesi, J. (2020) Low dose brain irradiation reduces amyloid-β and tau in 3xTg-AD mice, J. Alzheimer's Dis., 75, 15-21, doi: 10.3233/jad-200030.
  25. Iacono, D., Murphy, E. K., Stimpson, C. D., Perl, D. P., and Day, R. M. (2023) Low-dose brain radiation: lowering hyperphosphorylated-tau without increasing DNA damage or oncogenic activation, Sci. Rep., 13, doi: 10.1038/s41598-023-48146-w.
  26. Bevelacqua, J. J., and Mortazavi, S. M. J. (2018) Alzheimer 's disease: possible mechanisms behind neurohormesis induced by exposure to low doses of ionizing radiation, J. Biomed. Physics Engin., 8, 153-156.
  27. Rola, R., Fishman, K., Baure, J., Rosi, S., Lamborn, K. R., Obenaus, A., Nelson, G. A., and Fike, J. R. (2008) Hippocampal neurogenesis and neuroinflammation after cranial irradiation with (56)Fe particles, Radiat. Res., 169, 626-632, doi: 10.1667/RR1263.1.
  28. Vlkolinsky, R., Krucker, T., Nelson, G. A., and Obenaus, A. (2008) (56)Fe-particle radiation reduces neuronal output and attenuates lipopolysaccharide-induced inhibition of long-term potentiation in the mouse hippocampus, Radiat. Res., 169, 523-530, doi: 10.1667/RR1228.1.
  29. Liu, B., Hinshaw, R. G., Le, K. X., Park, M. A., Wang, S., Belanger, A. P., Dubey, S., Frost, J. L., Shi, Q., Holton, P., Trojanczyk, L., Reiser, V., Jones, P. A., Trigg, W., Di Carli, M. F., Lorello, P., Caldarone, B. J., Williams, J. P., O'Banion, M. K., and Lemere, C. A. (2019) Space-like (56)Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer's-like transgenic mice, Sci. Rep., 9, 12118, doi: 10.1038/s41598-019-48615-1.
  30. Kokhan, V. S., and Dobynde, M. I. (2023) The effects of galactic cosmic rays on the central nervous system: from negative to unexpectedly positive effects that astronauts may encounter, Biology (Basel), 12, doi: 10.3390/biology12030400.
  31. Capilla-Gonzalez, V., Guerrero-Cazares, H., Bonsu, J. M., Gonzalez-Perez, O., Achanta, P., Wong, J., Garcia-Verdugo, J. M., and Quinones-Hinojosa, A. (2014) The subventricular zone is able to respond to a demyelinating lesion after localized radiation, Stem Cells, 32, 59-69, doi: 10.1002/stem.1519.
  32. Mao, X. W., Nishiyama, N. C., Pecaut, M. J., Campbell-Beachler, M., Gifford, P., Haynes, K. E., Becronis, C., and Gridley, D. S. (2016) Simulated microgravity and low-dose/low-dose-rate radiation induces oxidative damage in the mouse brain, Radiat. Res., 185, 647-657, doi: 10.1667/RR14267.1.
  33. Kokhan, V. S., Lebedeva-Georgievskaya, K. B., Kudrin, V. S., Bazyan, A. S., Maltsev, A. V., and Shtemberg, A. S. (2019) An investigation of the single and combined effects of hypogravity and ionizing radiation on brain monoamine metabolism and rats’ behavior, Life Sci. Space Res., 20, 12-19, doi: 10.1016/j.lssr.2018.11.003.
  34. Kokhan, V. S., Anokhin, P. K., Belov, O. V., and Gulyaev, M. V. (2019) Cortical glutamate/GABA imbalance after combined radiation exposure: relevance to human deep-space missions, Neuroscience, 416, 295-308, doi: 10.1016/j.neuroscience.2019.08.009.
  35. Kokhan, V. S., Pikalov, V. A., Chaprov, K., and Gulyaev, M. V. (2024) Combined ionizing radiation exposure by gamma rays and carbon-12 nuclei increases neurotrophic factor content and prevents age-associated decreases in the volume of the sensorimotor cortex in rats, Int. J. Mol. Sci., 25, doi: 10.3390/ijms25126725.
  36. Bush, A. I., Takeuchi, H., Iba, M., Inoue, H., Higuchi, M., Takao, K., Tsukita, K., Karatsu, Y., Iwamoto, Y., Miyakawa, T., Suhara, T., Trojanowski, J. Q., Lee, V. M. Y., and Takahashi, R. (2011) P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating, PLoS One, 6, doi: 10.1371/journal.pone.0021050.
  37. Chen, Y. (2005) Specific tau phosphorylation sites in hippocampus correlate with impairment of step-down inhibitory avoidance task in rats, Behav. Brain Res., 158, 277-284, doi: 10.1016/j.bbr.2004.09.007.
  38. Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., Atzori, C., Migheli, A., Crowther, R. A., Ghetti, B., Spillantini, M. G., and Goedert, M. (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein, J. Neurosci., 22, 9340-9351, doi: 10.1523/JNEUROSCI.22-21-09340.2002.
  39. Peters, O. M., Connor-Robson, N., Sokolov, V. B., Aksinenko, A. Y., Kukharsky, M. S., Bachurin, S. O., Ninkina, N., and Buchman, V. L. (2013) Chronic administration of dimebon ameliorates pathology in TauP301S transgenic mice, J. Alzheimer's Dis., 33, 1041-1049, doi: 10.3233/JAD-2012-121732.
  40. Altman, D. G., and Bland, J. M. (2005) Treatment allocation by minimisation, BMJ, 330, doi: 10.1136/bmj.330.7495.843.
  41. Luong, T. N., Carlisle, H. J., Southwell, A., and Patterson, P. H. (2011) Assessment of motor balance and coordination in mice using the balance beam, J. Vis. Exp., 2376, doi: 10.3791/2376.
  42. Roemers, P., Mazzola, P. N., De Deyn, P. P., Bossers, W. J., van Heuvelen, M. J. G., and van der Zee, E. A. (2018) Burrowing as a novel voluntary strength training method for mice: a comparison of various voluntary strength or resistance exercise methods, J. Neurosci. Methods, 300, 112-126, doi: 10.1016/j.jneumeth.2017.05.027.
  43. Chicheva, M. M., Mal'tsev, A. V., Kokhan, V. S., and Bachurin, S. O. (2020) The effect of ionizing radiation on cognitive functions in mouse models of Alzheimer's disease, Doklady Biol. Sci., 494, 225-227, doi: 10.1134/S0012496620050026.
  44. Kokhan, V. S., Chaprov, K., Abaimov, D. A., Nesterov, M. S., and Pikalov, V. A. (2024) Combined irradiation by gamma-rays and carbon-12 nuclei caused hyperlocomotion and change in striatal metabolism of rats, Life Sci. Space Res., 44, 99-107, doi: 10.1016/j.lssr.2024.08.005.
  45. Cuttler, J. M., Moore, E. R., Hosfeld, V. D., and Nadolski, D. L. (2018) Second update on a patient with Alzheimer’s disease treated by CT scans, Dose Response, 16, 1559325818756461, doi: 10.1177/1559325818756461.
  46. Cuttler, J. M., Abdellah, E., Goldberg, Y., Al-Shamaa, S., Symons, S. P., Black, S. E., Freedman, M., and Korczyn, A. (2021) Low doses of ionizing radiation as a treatment for Alzheimer’s disease: a pilot study, J. Alzheimer's Dis., 80, 1119-1128, doi: 10.3233/jad-200620.
  47. Fan, Y., Liu, Z., Weinstein, P. R., Fike, J. R., and Liu, J. (2007) Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation, Eur. J. Neurosci., 25, 38-46, doi: 10.1111/j.1460-9568.2006.05269.x.
  48. Balentova, S., and Adamkov, M. (2015) Molecular, cellular and functional effects of radiation-induced brain injury: a review, Int. J. Mol. Sci., 16, 27796-27815, doi: 10.3390/ijms161126068.
  49. Raber, J., Yamazaki, J., Torres, E. R. S., Kirchoff, N., Stagaman, K., Sharpton, T., Turker, M. S., and Kronenberg, A. (2019) Combined effects of three high-energy charged particle beams important for space flight on brain, behavioral and cognitive endpoints in B6D2F1 female and male mice, Front. Physiol., 10, 179, doi: 10.3389/fphys.2019.00179.
  50. Filiou, M. D., Arefin, A. S., Moscato, P., and Graeber, M. B. (2014) ‘Neuroinflammation’ differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared, Neurogenetics, 15, 201-212, doi: 10.1007/s10048-014-0409-x.
  51. Osman, A. M., Sun, Y., Burns, T. C., He, L., Kee, N., Oliva-Vilarnau, N., Alevyzaki, A., Zhou, K., Louhivuori, L., Uhlén, P., Hedlund, E., Betsholtz, C., Lauschke, V. M., Kele, J., and Blomgren, K. (2020) Radiation triggers a dynamic sequence of transient microglial alterations in juvenile brain, Cell Rep., 31, doi: 10.1016/j.celrep.2020.107699.
  52. Rauf, A., Badoni, H., Abu-Izneid, T., Olatunde, A., Rahman, M. M., Painuli, S., Semwal, P., Wilairatana, P., and Mubarak, M. S. (2022) Neuroinflammatory markers: key indicators in the pathology of neurodegenerative diseases, Molecules, 27, 3194, doi: 10.3390/molecules27103194.
  53. Shahidehpour, R. K., Nelson, P. T., Katsumata, Y., and Bachstetter, A. D. (2024) Exploring the link between dystrophic microglia and the spread of Alzheimer's neuropathology, Brain, 148, 89-101, doi: 10.1093/brain/awae258.
  54. Streit, W. J., Braak, H., Xue, Q.-S., and Bechmann, I. (2009) Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease, Acta Neuropathol., 118, 475-485, doi: 10.1007/s00401-009-0556-6.
  55. Shahidehpour, R. K., Higdon, R. E., Crawford, N. G., Neltner, J. H., Ighodaro, E. T., Patel, E., Price, D., Nelson, P. T., and Bachstetter, A. D. (2021) Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain, Neurobiol. Aging, 99, 19-27, doi: 10.1016/j.neurobiolaging.2020.12.003.
  56. Kwon, H. S., and Koh, S.-H. (2020) Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes, Translat. Neurodegener., 9, doi: 10.1186/s40035-020-00221-2.
  57. Rexach, J. E., Polioudakis, D., Yin, A., Swarup, V., Chang, T. S., Nguyen, T., Sarkar, A., Chen, L., Huang, J., Lin, L.-C., Seeley, W., Trojanowski, J. Q., Malhotra, D., and Geschwind, D. H. (2020) Tau pathology drives dementia risk-associated gene networks toward chronic inflammatory states and immunosuppression, Cell Rep., 33, doi: 10.1016/j.celrep.2020.108398.
  58. Koca, S., Kiris, I., Sahin, S., Cinar, N., Karsidag, S., Hanagasi, H. A., Yildiz, G. B., and Tarik Baykal, A. (2022) Decreased levels of cytokines implicate altered immune response in plasma of moderate-stage Alzheimer’s disease patients, Neurosci. Lett., 786, doi: 10.1016/j.neulet.2022.136799.
  59. Vichaya, E. G., Malik, S., Sominsky, L., Ford, B. G., Spencer, S. J., and Dantzer, R. (2020) Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats, J. Neuroinflamm., 17, 172, doi: 10.1186/s12974-020-01832-2.
  60. Yamazaki, S., Bonsall, D. R., Kim, H., Tocci, C., Ndiaye, A., Petronzio, A., McKay-Corkum, G., Molyneux, P. C., Scammell, T. E., and Harrington, M. E. (2015) Suppression of locomotor activity in female C57Bl/6J mice treated with interleukin-1β: investigating a method for the study of fatigue in laboratory animals, PLoS One, 10, doi: 10.1371/journal.pone.0140678.
  61. Stojakovic, A., Paz-Filho, G., Arcos-Burgos, M., Licinio, J., Wong, M.-L., and Mastronardi, C. A. (2016) Role of the IL-1 pathway in dopaminergic neurodegeneration and decreased voluntary movement, Mol. Neurobiol., 54, 4486-4495, doi: 10.1007/s12035-016-9988-x.
  62. Hill, F., Kim, C. F., Gorrie, C. A., and Moalem-Taylor, G. (2011) Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice, Neurosci. Lett., 487, 363-367, doi: 10.1016/j.neulet.2010.10.057.
  63. Munshi, S., Parrilli, V., and Rosenkranz, J. A. (2019) Peripheral anti-inflammatory cytokine Interleukin-10 treatment mitigates interleukin-1β – induced anxiety and sickness behaviors in adult male rats, Behav. Brain Res., 372, 112024, doi: 10.1016/j.bbr.2019.112024.
  64. Richwine, A. F., Sparkman, N. L., Dilger, R. N., Buchanan, J. B., and Johnson, R. W. (2009) Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide, Brain Behav. Immun., 23, 794-802, doi: 10.1016/j.bbi.2009.02.020.
  65. Mrak, R. E., and Griffin, W. S. T. (2000) Interleukin-1 and the immunogenetics of Alzheimer disease, J. Neuropathol. Exp. Neurol., 59, 471-476, doi: 10.1093/jnen/59.6.471.
  66. Shaftel, S. S., Griffin, W. S. T., and O'Banion, M. K. (2008) The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective, J. Neuroinflamm., 5, doi: 10.1186/1742-2094-5-7.
  67. Boraschi, D., Italiani, P., Migliorini, P., and Bossù, P. (2023) Cause or consequence? The role of IL-1 family cytokines and receptors in neuroinflammatory and neurodegenerative diseases, Front. Immunol., 14, doi: 10.3389/fimmu.2023.1128190.
  68. Kaushal, V., Dye, R., Pakavathkumar, P., Foveau, B., Flores, J., Hyman, B., Ghetti, B., Koller, B. H., and LeBlanc, A. C. (2015) Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation, Cell Death Differ., 22, 1676-1686, doi: 10.1038/cdd.2015.16.
  69. Roy, E. R., Wang, B., Wan, Y. W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., Lee, V. M., Trojanowski, J. Q., Ginsberg, S. D., Butovsky, O., Zheng, H., and Cao, W. (2020) Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease, J. Clin. Invest., 130, 1912-1930, doi: 10.1172/JCI133737.
  70. Rachal Pugh, C., Fleshner, M., Watkins, L. R., Maier, S. F., and Rudy, J. W. (2001) The immune system and memory consolidation: a role for the cytokine IL-1beta, Neurosci. Biobehav. Rev., 25, 29-41, doi: 10.1016/s0149-7634(00)00048-8.
  71. Shaftel, S. S., Carlson, T. J., Olschowka, J. A., Kyrkanides, S., Matousek, S. B., and O'Banion, M. K. (2007) Chronic interleukin-1beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration, J. Neurosci., 27, 9301-9309, doi: 10.1523/JNEUROSCI.1418-07.2007.
  72. Rivera-Escalera, F., Pinney, J. J., Owlett, L., Ahmed, H., Thakar, J., Olschowka, J. A., Elliott, M. R., and O'Banion, M. K. (2019) IL-1beta-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia, J. Neuroinflamm., 16, 261, doi: 10.1186/s12974-019-1645-7.
  73. Shaftel, S. S., Kyrkanides, S., Olschowka, J. A., Miller, J. N., Johnson, R. E., and O'Banion, M. K. (2007) Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology, J. Clin. Invest., 117, 1595-1604, doi: 10.1172/JCI31450.
  74. Luo, X. J., Li, M., Huang, L., Nho, K., Deng, M., Chen, Q., Weinberger, D. R., Vasquez, A. A., Rijpkema, M., Mattay, V. S., Saykin, A. J., Shen, L., Fernandez, G., Franke, B., Chen, J. C., Chen, X. N., Wang, J. K., Xiao, X., Qi, X. B., Xiang, K., et al. (2012) The interleukin 3 gene (IL3) contributes to human brain volume variation by regulating proliferation and survival of neural progenitors, PLoS One, 7, e50375, doi: 10.1371/journal.pone.0050375.
  75. Zambrano, A., Otth, C., Mujica, L., Concha, I. I., and Maccioni, R. B. (2007) Interleukin-3 prevents neuronal death induced by amyloid peptide, BMC Neurosci., 8, 82, doi: 10.1186/1471-2202-8-82.
  76. Zambrano, A., Otth, C., Maccioni, R. B., and Concha, I. I. (2010) IL-3 controls tau modifications and protects cortical neurons from neurodegeneration, Curr. Alzheimer Res., 7, 615-624, doi: 10.2174/156720510793499011.
  77. McAlpine, C. S., Park, J., Griciuc, A., Kim, E., Choi, S. H., Iwamoto, Y., Kiss, M. G., Christie, K. A., Vinegoni, C., Poller, W. C., Mindur, J. E., Chan, C. T., He, S., Janssen, H., Wong, L. P., Downey, J., Singh, S., Anzai, A., Kahles, F., Jorfi, M., et al. (2021) Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease, Nature, 595, 701-706, doi: 10.1038/s41586-021-03734-6.
  78. Wharton, W., Kollhoff, A. L., Gangishetti, U., Verble, D. D., Upadhya, S., Zetterberg, H., Kumar, V., Watts, K. D., Kippels, A. J., Gearing, M., Howell, J. C., Parker, M. W., and Hu, W. T. (2019) Interleukin 9 alterations linked to alzheimer disease in african americans, Ann. Neurol., 86, 407-418, doi: 10.1002/ana.25543.
  79. Donninelli, G., Saraf-Sinik, I., Mazziotti, V., Capone, A., Grasso, M. G., Battistini, L., Reynolds, R., Magliozzi, R., and Volpe, E. (2020) Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain, J. Neuroinflamm., 17, 149, doi: 10.1186/s12974-020-01770-z.
  80. Meng, H., Niu, R., You, H., Wang, L., Feng, R., Huang, C., and Li, J. (2021) Interleukin-9 attenuates inflammatory response and hepatocyte apoptosis in alcoholic liver injury, Life Sci., 288, 120180, doi: 10.1016/j.lfs.2021.120180.
  81. Singhera, G. K., MacRedmond, R., and Dorscheid, D. R. (2008) Interleukin-9 and -13 inhibit spontaneous and corticosteroid induced apoptosis of normal airway epithelial cells, Exp. Lung Res., 34, 579-598, doi: 10.1080/01902140802369372.
  82. Brigas, H. C., Ribeiro, M., Coelho, J. E., Gomes, R., Gomez-Murcia, V., Carvalho, K., Faivre, E., Costa-Pereira, S., Darrigues, J., de Almeida, A. A., Buee, L., Dunot, J., Marie, H., Pousinha, P. A., Blum, D., Silva-Santos, B., Lopes, L. V., and Ribot, J. C. (2021) IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer's disease, Cell Rep., 36, 109574, doi: 10.1016/j.celrep.2021.109574.
  83. Yang, J., Kou, J., Lalonde, R., and Fukuchi, K. I. (2017) Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer's disease, Brain Behav. Immun., 65, 262-273, doi: 10.1016/j.bbi.2017.05.012.
  84. Porro, C., Cianciulli, A., and Panaro, M. A. (2020) The regulatory role of IL-10 in neurodegenerative diseases, Biomolecules, 10, doi: 10.3390/biom10071017.
  85. Sharma, S., Yang, B., Xi, X., Grotta, J. C., Aronowski, J., and Savitz, S. I. (2011) IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways, Brain Res., 1373, 189-194, doi: 10.1016/j.brainres.2010.11.096.
  86. Ajoy, R., Lo, Y. C., Ho, M. H., Chen, Y. Y., Wang, Y., Chen, Y. H., Jing-Yuan, C., Changou, C. A., Hsiung, Y. C., Chen, H. M., Chang, T. H., Lee, C. Y., Chiang, Y. H., Chang, W. C., Hoffer, B., and Chou, S. Y. (2021) CCL5 promotion of bioenergy metabolism is crucial for hippocampal synapse complex and memory formation, Mol. Psychiatry, 26, 6451-6468, doi: 10.1038/s41380-021-01103-3.
  87. Ho, M. H., Yen, C. H., Hsieh, T. H., Kao, T. J., Chiu, J. Y., Chiang, Y. H., Hoffer, B. J., Chang, W. C., and Chou, S. Y. (2021) CCL5 via GPX1 activation protects hippocampal memory function after mild traumatic brain injury, Redox Biol., 46, 102067, doi: 10.1016/j.redox.2021.102067.
  88. Shinohara, C., Gobbel, G. T., Lamborn, K. R., Tada, E., and Fike, J. R. (1997) Apoptosis in the subependyma of young adult rats after single and fractionated doses of X-rays, Cancer Res., 57, 2694-2702.
  89. Mizumatsu, S., Monje, M. L., Morhardt, D. R., Rola, R., Palmer, T. D., and Fike, J. R. (2003) Extreme sensitivity of adult neurogenesis to low doses of X-irradiation, Cancer Res., 63, 4021-4027.
  90. Bettcher, B. M., Fitch, R., Wynn, M. J., Lalli, M. A., Elofson, J., Jastrzab, L., Mitic, L., Miller, Z. A., Rabinovici, G. D., Miller, B. L., Kao, A. W., Kosik, K. S., and Kramer, J. H. (2016) MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes, Alzheimers Dement. (Amst), 3, 91-97, doi: 10.1016/j.dadm.2016.05.004.
  91. Wang, F., Baba, N., Shen, Y., Yamashita, T., Tsuru, E., Tsuda, M., Maeda, N., and Sagara, Y. (2017) CCL11 promotes migration and proliferation of mouse neural progenitor cells, Stem Cell Res. Ther., 8, 26, doi: 10.1186/s13287-017-0474-9.
  92. Azizi, G., Khannazer, N., and Mirshafiey, A. (2014) The potential role of chemokines in Alzheimer's disease pathogenesis, Am. J. Alzheimer's Dis. Other Dement., 29, 415-425, doi: 10.1177/1533317513518651.
  93. Yang, X., Gao, L., Wu, X., Zhang, Y., and Zang, D. (2016) Increased levels of MIP-1α in CSF and serum of ALS, Acta Neurol. Scand., 134, 94-100, doi: 10.1111/ane.12513.

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