Baiq Risky Wahyu Lisnasari, Chrismawan Ardianto, Junaidi Khotib
Baiq Risky Wahyu Lisnasari, Chrismawan Ardianto, Junaidi Khotib*
Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.
Volume - 15,
Issue - 7,
Year - 2022
Depression is a heterogeneous disorder with more than one possible etiologies. Currently, studies are mostly focused on neuronal dysfunction, while the involvement of other brain cells, such as microglia, has not been widely explored. This review aimed to systematically review the studies reporting the effect of microglia inhibitors on depressive-like behavior in rodent models, to obtained a better understanding of the effectiveness of the intervention against depression. The PubMed database was explored from January 2011 to April 2021 with related keywords for full-text publications reporting antidepressant effects of microglial inhibitor in rodents. We identified 713 research publications, of which only 25 studies met the inclusion criteria and were included for analysis. Administration of antidepressant drugs/compounds that inhibit microglia was reported to be beneficial because it improved depression-like symptoms by reducing outcomes based on immobility, anhedonia, and locomotor activity. Microglia inactivation has been reported to occur through inhibition of the HMGB1/TLR4/NF-B and NLRP3/NF-?B pathways, as well as improved communication of microglia neurons through increased interaction of CX3CL1 with CX3CR1. These data indicated that the use of an agent inhibiting microglia activity is promising as a strategy in overcoming depression in humans.
Cite this article:
Baiq Risky Wahyu Lisnasari, Chrismawan Ardianto, Junaidi Khotib. Microglia as a Potential Target for Antidepressant: A Systematic Review on Preclinical studies. Research Journal of Pharmacy and Technology. 2022;15(7):3317-3. doi: 10.52711/0974-360X.2022.00555
Baiq Risky Wahyu Lisnasari, Chrismawan Ardianto, Junaidi Khotib. Microglia as a Potential Target for Antidepressant: A Systematic Review on Preclinical studies. Research Journal of Pharmacy and Technology. 2022;15(7):3317-3. doi: 10.52711/0974-360X.2022.00555 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-7-77
1. James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392(10159):1789–858. Available from: https://doi.org/10.1016/S0140-6736(18)32279-7.
2. Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015; 76(2):155–62. Available from: https://doi.org/10.4088/JCP.14m09298.
3. Sangroyangla, Temjentula, Imchen T, Longkumer T, Vizayieno, Murry K. Prevalence of Depression and the associated risk factors among the Elderly. Asian J Nurs Educ Res. 2019; 9(4):552. Available from: https://doi.org/10.5958/2349-2996.2019.00119.8.
4. Sonia Devi, Suman, Dr. Santosh Gurjar. a Comparative Study To Assess the Level of Depression Between Elderly Living At Old Age Home and Living With Families in Haryana. EPRA Int J Multidiscip Res. 2020; 2(March):102–6. doi: 10.36713/epra5119.
5. Joshi R, Hugo V. A Study to Assess the Level of Depression among Old Age People in Selected Villages in Mehsana District , Gujarat. Int J Nurs Educ Res. 2014; 2(December):379–80. ISSN: 2347–8640
6. Kumar D. Comorbid Depression in Inflammatory Bowel Disease. Asian J Res Pharm Sci. 2020; 10(1):35. doi: 10.5958/2231-5659.2020.00008.9.
7. Vijayalakshmi K. Assessment of Depression among Cancer Patients. Asian J Nurs Educ Res. 2018; 8(1):11. doi: 10.5958/2349-2996.2018.00004.6.
8. Patel M, Patel C, Patel D, Anand I, Patel C. A Review on Novel Strategies for Pharmacotherapy of Depression. Res J Pharmacol Pharmacodyn. 2010; 2(2):153-159–159. ISSN: 0975-4407.
9. Bhagat V, Bin Symbak N, Husain R, Mat KC. The role of selective serotonin reuptake inhibitors and cognitive behavioral therapy in preventing relapse of major depressive disorder. Res J Pharm Technol. 2019; 12(8):3818–24. doi: 10.5958/0974-360X.2019.00654.1.
10. Kan K, Feenstra TL, de Vries SO, Visser E, Schoevers RA, Jörg F. The clinical effectiveness of an algorithm-guided treatment program for depression in specialized mental healthcare: A comparison with efficacy trials. J Affect Disord [Internet]. 2020; 275(September 2019):216–23. Available from: https://doi.org/10.1016/j.jad.2020.07.010
11. Deng S long, Chen J guo, Wang F. Microglia: A Central Player in Depression. Curr Med Sci. 2020; 40(3):391–400. doi: 10.1007/s11596-020-2193-1.
12. Brites D, Fernandes A. Neuroinflammation and depression: Microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci. 2015; 9(DEC):1–20. doi 10.3389/fncel.2015.00476.
13. Yirmiya R, Rimmerman N, Reshef R. Depression as a Microglial Disease. Trends Neurosci. 2015; 38(10):637–58. doi: 10.1016/j.tins.2015.08.001.
14. Jia X, Gao Z, Hu H. Microglia in depression: current perspectives. Sci China Life Sci. 2020; 64(6):911–25. doi: 10.1007/s11427-020-1815-6.
15. Zhang L, Zhang J, You Z. Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder. Front Cell Neurosci. 2018; 12(October):1–13. doi: 10.3389/fncel.2018.00306.
16. Singhal G, Baune BT. Microglia: An interface between the loss of neuroplasticity and depression. Front Cell Neurosci. 2017; 11(September):1–16. doi: 10.3389/fncel.2017.00270.
17. Jurga AM, Paleczna M, Kuter KZ. Overview of General and Discriminating Markers of Differential Microglia Phenotypes. Front Cell Neurosci. 2020; 14(August):1–18. doi: 10.3389/fncel.2020.00198.
18. Stein DJ, Vasconcelos MF, Albrechet-souza L, Ceresér KMM, de Almeida RMM. Microglial Over-Activation by Social Defeat Stress Contributes to Anxiety-. Front Behav Neurosci. 2017; 11(207):1–10. doi: 10.3389/fnbeh.2017.00207.
19. Hinwood M, Morandini J, Day TA, Walker FR. Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex. Cereb Cortex. 2011; 22:1442–54. doi: 10.1093/cercor/bhr229.
20. Wang YL, Han QQ, Gong WQ, Pan DH, Wang LZ, Hu W, et al. Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats. J Neuroinflammation. 2018; 15(1):1–14. doi: 10.1186/s12974-018-1054-3.
21. Xu X, Xiao X, Yan Y, Zhang T. Activation of liver X receptors prevents emotional and cognitive dysfunction by suppressing microglial M1-polarization and restoring synaptic plasticity in the hippocampus of mice. Brain Behav Immun [Internet]. 2021; 94(February):111–24. Available from: https://doi.org/10.1016/j.bbi.2021.02.026
22. Cheng J, Chen M, Wan HQ, Chen XQ, Li CF, Zhu JX, et al. Paeoniflorin exerts antidepressant-like effects through enhancing neuronal FGF-2 by microglial inactivation. J Ethnopharmacol [Internet]. 2021; 274(February):114046. Available from: https://doi.org/10.1016/j.jep.2021.114046
23. Feng R, He MC, Li Q, Liang XQ, Tang DZ, Zhang JL, et al. Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive-like behaviors by suppressing neuroinflammation in hypothalamus of mice. Phyther Res. 2020; 34(12):3273–86. doi: 10.1002/ptr.6777.
24. Zhang J, Yi S, Li Y, Xiao C, Liu C, Jiang W, et al. The antidepressant effects of asperosaponin Ⅵ are mediated by the suppression of microglial activation and reduction of TLR4/NF-ĸB induced IDO expression. Psychopharmacology (Berl). 2020. doi: 10.1101/2020.03.15.992529.
25. Su J, Pan YW, Wang SQ, Li XZ, Huang F, Ma SP. Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation. Int Immunopharmacol [Internet]. 2020; 80(December 2019):106181. Available from: https://doi.org/10.1016/j.intimp.2019.106181
26. Guo Y, Gan X, Zhou H, Zhou H, Pu S, Long X, et al. Fingolimod suppressed the chronic unpredictable mild stress-induced depressive-like behaviors via affecting microglial and NLRP3 inflammasome activation. Life Sci [Internet]. 2020; 263(July):118582. Available from: https://doi.org/10.1016/j.lfs.2020.118582
27. Zhou S, Chen S, Xie W, Guo X, Zhao J. Microglia polarization of hippocampus is involved in the mechanism of Apelin-13 ameliorating chronic water immersion restraint stress-induced depression-like behavior in rats. Neuropeptides [Internet]. 2020; 81(January):102006. Available from: https://doi.org/10.1016/j.npep.2020.102006
28. Habib MZ, Ebeid MA, el Faramawy Y, Saad SST, El Magdoub HM, Attia AA, et al. Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/β-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats [Internet]. Vol. 399, Toxicology and Applied Pharmacology. Elsevier Inc; 2020. 115073 p. Available from: https://doi.org/10.1016/j.taap.2020.115073
29. Mao ZF, Ouyang SH, Zhang QY, Wu YP, Wang GE, Tu LF, et al. New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation. FASEB J. 2020; 34(8):10998–1014. doi: 10.1096/fj.202000146RR
30. Xu X, Piao HN, Aosai F, Zeng XY, Cheng JH, Cui YX, et al. Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways. Vol. 177, British Journal of Pharmacology. 2020. 5224–5245 p. doi: 10.1111/bph.15261.
31. Chen T, Zheng M, Li Y, Liu S, He L. The role of CCR5 in the protective effect of Esculin on lipopolysaccharide-induced depressive symptom in mice. J Affect Disord [Internet]. 2020; 277(March):755–64. Available from: https://doi.org/10.1016/j.jad.2020.08.065
32. Feng X, Fan Y, Chung CY. Mefenamic acid can attenuate depressive symptoms by suppressing microglia activation induced upon chronic stress. Brain Res [Internet]. 2020; 1740(October 2019):146846. Available from: https://doi.org/10.1016/j.brainres.2020.146846
33. Han Y, Zhang L, Wang Q, Zhang D, Zhao Q, Zhang J, et al. Minocycline inhibits microglial activation and alleviates depressive-like behaviors in male adolescent mice subjected to maternal separation. Psychoneuroendocrinology [Internet]. 2019; 107(April):37–45. Available from: https://doi.org/10.1016/j.psyneuen.2019.04.021
34. Wang B, Huang X, Pan X, Zhang T, Hou C, Su WJ, et al. Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons. Brain Behav Immun [Internet]. 2020; 88:132–43. Available from: https://doi.org/10.1016/j.bbi.2020.06.019
35. Zhang C, Zhang YP, Li YY, Liu BP, Wang HY, Li KW, et al. Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat. Behav Brain Res. 2019; 356:348–57. doi: 10.1016/j.bbr.2018.07.001
36. Zheng LS, Kaneko N, Sawamoto K. Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice. Front Cell Neurosci. 2015; 9(JAN):1–10. doi: 10.3389/fncel.2015.00005
37. Wang HT, Huang FL, Hu ZL, Zhang WJ, Qiao XQ, Huang YQ, et al. Early-Life Social Isolation-Induced Depressive-Like Behavior in Rats Results in Microglial Activation and Neuronal Histone Methylation that Are Mitigated by Minocycline. Neurotox Res [Internet]. 2017; 31(4):505–20. Available from: http://dx.doi.org/10.1007/s12640-016-9696-3
38. He M chao, Shi Z, Sha N nan, Chen N, Peng S yu, Liao D fang, et al. Paricalcitol alleviates lipopolysaccharide-induced depressive-like behavior by suppressing hypothalamic microglia activation and neuroinflammation. Biochem Pharmacol [Internet]. 2019; 163(January):1–8. Available from: https://doi.org/10.1016/j.bcp.2019.01.021
39. Ito N, Hirose E, Ishida T, Hori A, Nagai T, Kobayashi Y, et al. Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice. J Neuroinflammation. 2017; 14(1):1–15. doi: 10.1186/s12974-017-0876-8
40. Vega-Rivera NM, Ortiz-López L, Granados-Juárez A, Estrada-Camarena EM, Ramírez-Rodríguez GB. Melatonin Reverses the Depression-associated Behaviour and Regulates Microglia, Fractalkine Expression and Neurogenesis in Adult Mice Exposed to Chronic Mild Stress. Neuroscience. 2020; 440:316–36. doi: 10.1016/j.neuroscience.2020.05.014
41. Weng L, Dong S, Wang S, Yi L, Geng D. Macranthol attenuates lipopolysaccharide-induced depressive-like behaviors by inhibiting neuroinflammation in prefrontal cortex. Physiol Behav [Internet]. 2019; 204(September 2018):33–40. Available from: https://doi.org/10.1016/j.physbeh.2019.02.010
42. Yamawaki Y, Yoshioka N, Nozaki K, Ito H, Oda K, Harada K, et al. Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice. Brain Res [Internet]. 2018; 1680:13–38. Available from: https://doi.org/10.1016/j.brainres.2017.12.004
43. Zhang J, Xie X, Tang M, Zhang J, Zhang B, Zhao Q, et al. Salvianolic acid B promotes microglial M2-polarization and rescues neurogenesis in stress-exposed mice. Brain Behav Immun [Internet]. 2017; 66:111–24. Available from: http://dx.doi.org/10.1016/j.bbi.2017.07.012
44. Zhang JQ, Wu XH, Feng Y, Xie XF, Fan YH, Yan S, et al. Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice: Involvement of the neuroinflammatory pathway. Acta Pharmacol Sin [Internet]. 2016; 37(9):1141–53. Available from: http://dx.doi.org/10.1038/aps.2016.63
45. Zhao Q, Wu X, Yan S, Xie X, Fan Y, Zhang J, et al. The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARγ-mediated alteration of microglial activation phenotypes. J Neuroinflammation [Internet]. 2016; 13(1):1–17. Available from: http://dx.doi.org/10.1186/s12974-016-0728-y
46. Pollak DD, Rey CE, Monje FJ. Rodent models in depression research: Classical strategies and new directions. Ann Med. 2010; 42(4):252–64. doi: 10.3109/07853891003769957
47. Anggreini P, Ardianto C, Rahmadi M, Khotib J. Quercetin attenuates acute predator stress exposure-evoked innate fear and behavioral perturbation. J Basic Clin Physiol Pharmacol. 2020; 30(6):1–7. doi: 10.1515/jbcpp-2019-0242
48. Velraj M, Vijayalakshmi A, Jayakumari S. Antidepressant-Like Effects of the Ethanolic Extract of Albizzia lebbeck (Linn) Leaves in Animal Models of Depression. Res J Pharmacogn Phytochem. 2010; 2(1):30–3. ISSN: 0975- 2331.
49. Lakshmi JA, Satyavthi D. Evaluation of Anti Depressant and MAO Inhibitory Activity of Rhodiola rhodantha rhizome methanolic extract . Res J Pharm Technol. 2015; 8(3):310. doi: 10.5958/0974-360x.2015.00051.7
50. Mahmudah R, Hasanuddin S, Saleh A, Yuliastri WO, Isrul M. Antidepressant activity and identification of chemical compounds extract mustard leaves (Brassica juncea l.). Res J Pharm Technol. 2019; 12(7):3223–7. doi: 10.5958/0974-360X.2019.00542.0
51. Fruyt J De. Anhedonia in Depressive Disorder : A Narrative Review. Psychopathology. 2020; 53:274–81. doi: 10.1159/000508773
52. Buckner JD, Joiner TE, Pettit JW, Lewinsohn PM, Schmidt NB. Implications of the DSM ’ s emphasis on sadness and anhedonia in major depressive disorder. Psychiatry Res. 2008; 159:25–30. doi: 10.1016/j.psychres.2007.05.010
53. Schmidt M V, Planck M. Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease. Front Behav Neurosci. 2014; 8(April):1–18. doi: 10.3389/fnbeh.2014.00133
54. Gomathi S, Shanmuga Sundaram R, Vijayabaskaran M, Kannan C, Sambathkumar R. Pedalium murex linn leaves against LPS-induced oxidative stress, anxiety and depression behavioural alterations in rats. Res J Pharm Technol. 2017; 10(5):1333–8. doi: 10.5958/0974-360X.2017.00236.0.
55. Colton CA, Wilcock DM. Assessing Activation States in Microglia. CNS Neurol Disord - Drug Targets. 2010; 9(2):174–91. doi: 10.2174/187152710791012053
56. Yao L, Kan EM, Lu J, Hao A, Dheen ST, Kaur C, et al. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: Role of TLR4 in hypoxic microglia. J Neuroinflammation. 2013; 10:1–21. doi: 10.1186/1742-2094-10-23
57. Wang H, Song X, Li M, Wang X, Tao Y, Xiya X, et al. The role of TLR4/NF-κB signaling pathway in activated microglia of rats with chronic high intraocular pressure and vitro scratch injury-induced microglia. Int Immunopharmacol [Internet]. 2020; 83(March):106395. Available from: https://doi.org/10.1016/j.intimp.2020.106395
58. Eyo UB, Wu LJ. Bidirectional microglia-neuron communication in the healthy brain. Neural Plast. 2013; 2013. doi: 10.1155/2013/456857
59. Paolicelli RC, Bisht K, Tremblay MÈ. Fractalkine regulation of microglial physiology and consequences on the brain and behavior. Front Cell Neurosci. 2014; 8(MAY):1–10. doi: 10.3389/fncel.2014.00129
60. Szepesi Z, Manouchehrian O, Bachiller S, Deierborg T. Bidirectional Microglia–Neuron Communication in Health and Disease. Front Cell Neurosci. 2018; 12(September):1–26. doi: 10.3389/fncel.2018.00323