Advertisement

Minocycline prevents the development of depression-like behavior and hippocampal inflammation in a rat model of Alzheimer’s disease

  • Mohammad Amani
  • Ghaffar Shokouhi
  • Ali-Akbar Salari
Original Investigation

Abstract

Rationale

Considerable clinical and experimental studies have shown that depression-related disorders are the most common neuropsychiatric symptoms in Alzheimer’s disease (AD), affecting as many as 20–40% of patients. An increasing amount of evidence shows that monoamine-based antidepressant treatments are not completely effective for depression treatment in patients with dementia. Minocycline, a second-generation tetracycline antibiotic, has been gaining research and clinical attention for the treatment of different neuropsychiatric disorders, and more recently depression symptom in humans.

Methods

In the present study, we investigated the effects of Aβ1–42 administration alone or in combination with minocycline treatment on depression-like behaviors and anti/pro-inflammatory cytokines such as interleukin(IL)-10, IL-β, and tumor necrosis factor (TNF)-α in the hippocampus of rats.

Results

Our results showed that Aβ1–42 administration increased depression-related behaviors in sucrose preference test, tail suspension test, novelty-suppressed feeding test, and forced swim test. We also found significant increases in IL-1β and TNF-α levels in the hippocampus of Aβ1–42-treated rats. Interestingly, minocycline treatment significantly reversed depression-related behaviors and the levels of hippocampal cytokines in Aβ1–42-treated rats.

Conclusion

These findings support the idea that there is a significant relationship among AD, depression-related symptoms, and pro-inflammatory cytokines in the brain, and suggest that antidepressant-like impacts of minocycline could be due to its anti-inflammatory properties. This drug could be of potential interest for the treatment of depression in patients with Alzheimer’s disease.

Keywords

Neurodegenerative disease Affective disorders Immune system β-Amyloid Antibiotics 

Notes

Compliance with ethical standards

All experiments were conducted under the recommended conditions of the Guide for the Care and Use of Laboratory Animals of the National Institute of Health (NIH).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aguzzi A, Barres BA, Bennett ML (2013) Microglia: scapegoat, saboteur, or something else? Science (80- ) 339:156–161CrossRefPubMedPubMedCentralGoogle Scholar
  2. Amorim D, Puga S, Bragança R, et al (2017) Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat. Behav Brain Res SreeTestContent 1 327:1–10CrossRefPubMedGoogle Scholar
  3. Ball MJ, Hachinski V, Fox A et al (1985) A new definition of Alzheimer’s disease: a hippocampal dementia. Lancet 325:14–16CrossRefGoogle Scholar
  4. Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, Bentham P, Fox C, Holmes C, Katona C, Knapp M, Lawton C, Lindesay J, Livingston G, McCrae N, Moniz-Cook E, Murray J, Nurock S, Orrell M, O'Brien J, Poppe M, Thomas A, Walwyn R, Wilson K, Burns A (2011) Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet 378:403–411CrossRefPubMedGoogle Scholar
  5. Benoit M, Berrut G, Doussaint J, Bakchine S, Bonin-Guillaume S, Frémont P, Gallarda T, Krolak-Salmon P, Marquet T, Mékiès C, Sellal F, Schuck S, David R, Robert P (2012) Apathy and depression in mild Alzheimer’s disease: a cross-sectional study using diagnostic criteria. J Alzheimers Dis 31:325–334CrossRefPubMedGoogle Scholar
  6. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157:115–118CrossRefPubMedGoogle Scholar
  7. Brosseron F, Krauthausen M, Kummer M, Heneka MT (2014) Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 50:534–544CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cacabelos R, Barquero M, Garcia P et al (1991) Cerebrospinal fluid interleukin-1 beta (IL-1 beta) in Alzheimer’s disease and neurological disorders. Methods Find Exp Clin Pharmacol 13:455–458PubMedGoogle Scholar
  9. Caraci F, Copani A, Nicoletti F, Drago F (2010) Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 626:64–71CrossRefPubMedGoogle Scholar
  10. Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B (2012) Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol 26:1185–1193CrossRefPubMedGoogle Scholar
  11. Chen J-H, Ke K-F, Lu J-H, Qiu YH, Peng YP (2015) Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1–42-induced Alzheimer’s disease model rats. PLoS One 10:e0116549CrossRefPubMedPubMedCentralGoogle Scholar
  12. Chen L, Li S, Cai J, Wei TJ, Liu LY, Zhao HY, Liu BH, Jing HB, Jin ZR, Liu M, Wan Y, Xing GG (2018) Activation of CRF/CRFR1 signaling in the basolateral nucleus of the amygdala contributes to chronic forced swim-induced depressive-like behaviors in rats. Behav Brain Res 338:134–142CrossRefPubMedGoogle Scholar
  13. Chen M, Ona VO, Li M et al (2000) Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 6:797CrossRefPubMedGoogle Scholar
  14. Chermat R, Thierry B, Mico JA et al (1986) Adaptation of the tail suspension test to the rat. Aust J Pharm 17:348–350Google Scholar
  15. Chi S, Wang C, Jiang T, Zhu XC, Yu JT, Tan L (2015) The prevalence of depression in Alzheimer’s disease: a systematic review and meta-analysis. Curr Alzheimer Res 12:189–198CrossRefPubMedGoogle Scholar
  16. Cioanca O, Hritcu L, Mihasan M, Trifan A, Hancianu M (2014) Inhalation of coriander volatile oil increased anxiolytic–antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1–42) rat model of Alzheimer’s disease. Physiol Behav 131:68–74CrossRefPubMedGoogle Scholar
  17. Colaianna M, Tucci P, Zotti M, Morgese MG, Schiavone S, Govoni S, Cuomo V, Trabace L (2010) Soluble βamyloid1-42: a critical player in producing behavioural and biochemical changes evoking depressive-related state? Br J Pharmacol 159:1704–1715CrossRefPubMedPubMedCentralGoogle Scholar
  18. Czirr E, Wyss-Coray T (2012) The immunology of neurodegeneration. J Clin Invest 122:1156–1163CrossRefPubMedPubMedCentralGoogle Scholar
  19. da Silva Dias IC, Carabelli B, Ishii DK, de Morais H, de Carvalho MC, Rizzo de Souza LE, Zanata SM, Brandão ML, Cunha TM, Ferraz AC, Cunha JM, Zanoveli JM (2016) Indoleamine-2, 3-dioxygenase/kynurenine pathway as a potential pharmacological target to treat depression associated with diabetes. Mol Neurobiol 53:6997–7009CrossRefPubMedGoogle Scholar
  20. de Godoy MA, de Souza AS, Lobo MA et al (2013) Effects of protein restriction during gestation and lactation on cell proliferation in the hippocampus and subventricular zone: functional implications. Protein restriction alters hippocampal/SVZ cell proliferation brain Res 1496:10–27PubMedGoogle Scholar
  21. Dean OM, Kanchanatawan B, Ashton M, et al (2017) Adjunctive minocycline treatment for major depressive disorder: a proof of concept trial. Aust New Zeal J Psychiatry 0004867417709357Google Scholar
  22. Dhabhar FS, Burke HM, Epel ES, Mellon SH, Rosser R, Reus VI, Wolkowitz OM (2009) Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression. J Psychiatr Res 43:962–969CrossRefPubMedGoogle Scholar
  23. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457CrossRefGoogle Scholar
  24. Du Y, Ma Z, Lin S et al (2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci 98:14669–14674CrossRefPubMedGoogle Scholar
  25. Emadi-Kouchak H, Mohammadinejad P, Asadollahi-Amin A, Rasoulinejad M, Zeinoddini A, Yalda A, Akhondzadeh S (2016) Therapeutic effects of minocycline on mild-to-moderate depression in HIV patients: a double-blind, placebo-controlled, randomized trial. Int Clin Psychopharmacol 31:20–26CrossRefPubMedGoogle Scholar
  26. Engedal K, Barca ML, Laks J, Selbaek G (2011) Depression in Alzheimer’s disease: specificity of depressive symptoms using three different clinical criteria. Int J Geriatr Psychiatry 26:944–951CrossRefPubMedGoogle Scholar
  27. Esmaeili MH, Bahari B, Salari A-A (2018) ATP-sensitive potassium-channel inhibitor glibenclamide attenuates HPA axis hyperactivity, depression- and anxiety-related symptoms in a rat model of Alzheimer’s disease. Brain Res Bull 137:. doi:  https://doi.org/10.1016/j.brainresbull.2018.01.001 CrossRefPubMedGoogle Scholar
  28. Filali M, Lalonde R, Rivest S (2009) Cognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer’s disease. Genes, Brain Behav 8:143–148CrossRefGoogle Scholar
  29. Francis-Oliveira J, Ponte B, Barbosa APM, Veríssimo LF, Gomes MV, Pelosi GG, de Britto LRG, Moreira EG (2013) Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats. Behav Brain Res 252:195–203CrossRefPubMedGoogle Scholar
  30. Garcez ML, Mina F, Bellettini-Santos T, Carneiro FG, Luz AP, Schiavo GL, Andrighetti MS, Scheid MG, Bolfe RP, Budni J (2017) Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice. Prog Neuro-Psychopharmacology Biol Psychiatry 77:23–31CrossRefGoogle Scholar
  31. Giuliani F, Fu SA, Metz LM, Yong VW (2005) Effective combination of minocycline and interferon-β in a model of multiple sclerosis. J Neuroimmunol 165:83–91CrossRefPubMedGoogle Scholar
  32. Goshen I, Kreisel T, Licht T et al (2008) Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13:717–728CrossRefPubMedGoogle Scholar
  33. Goulden V, Glass D, Cunliffe WJ (1996) Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol 134:693–695CrossRefPubMedGoogle Scholar
  34. Grammas P, Ovase R (2001) Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease. Neurobiol Aging 22:837–842CrossRefPubMedGoogle Scholar
  35. Guo J, Chang L, Li C, Li M, Yan P, Guo Z, Wang C, Zha Q, Wang Q (2017) Sb203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1–42 into hippocampus of mice. Metab Brain Dis 32:57–68CrossRefPubMedGoogle Scholar
  36. Hanlon LA, Huh JW, Raghupathi R (2016) Minocycline transiently reduces microglia/macrophage activation but exacerbates cognitive deficits following repetitive traumatic brain injury in the neonatal rat. J Neuropathol Exp Neurol 75:214–226CrossRefPubMedPubMedCentralGoogle Scholar
  37. Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, Wallin A, Minthon L, Blennow K (2010) Evaluation of plasma Aβ 40 and Aβ 42 as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging 31:357–367CrossRefPubMedGoogle Scholar
  38. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science (80- ) 297:353–356CrossRefPubMedGoogle Scholar
  39. Heneka MT, O’Banion MK (2007) Inflammatory processes in Alzheimer’s disease. J Neuroimmunol 184:69–91CrossRefPubMedGoogle Scholar
  40. Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, Sheridan JF, Godbout JP (2008) Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 5:15CrossRefPubMedPubMedCentralGoogle Scholar
  41. Hritcu L, Noumedem JA, Cioanca O, Hancianu M, Postu P, Mihasan M (2015) Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1–42) rat model of Alzheimer’s disease. Behav Brain Funct 11:13CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hu R, Wei P, Jin L, Zheng T, Chen WY, Liu XY, Shi XD, Hao JR, Sun N, Gao C (2017) Overexpression of EphB2 in hippocampus rescues impaired NMDA receptors trafficking and cognitive dysfunction in Alzheimer model. Cell Death Dis 8:e2717CrossRefPubMedPubMedCentralGoogle Scholar
  43. Izumi J, Washizuka M, Hayashi-Kuwabara Y, Yoshinaga K, Tanaka Y, Ikeda Y, Kiuchi Y, Oguchi K (1997) Evidence for a depressive-like state induced by repeated saline injections in Fischer 344 rats. Pharmacol Biochem Behav 57:883–888CrossRefPubMedGoogle Scholar
  44. Khundakar AA, Thomas AJ (2015) Neuropathology of depression in Alzheimer’s disease: current knowledge and the potential for new treatments. J Alzheimers Dis 44:27–41CrossRefPubMedGoogle Scholar
  45. Kohman RA, Rhodes JS (2013) Neurogenesis, inflammation and behavior. Brain Behav Immun 27:22–32CrossRefPubMedGoogle Scholar
  46. Kosari-Nasab M, Shokouhi G, Ghorbanihaghjo A, Abbasi MM, Salari AA (2018) Anxiolytic- and antidepressant-like effects of Silymarin compared to diazepam and fluoxetine in a mouse model of mild traumatic brain injury. Toxicol Appl Pharmacol 338:338–173.  https://doi.org/10.1016/j.taap.2017.11.012 CrossRefGoogle Scholar
  47. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M (2007) Minocycline treatment in acute stroke an open-label, evaluator-blinded study. Neurology 69:1404–1410CrossRefPubMedGoogle Scholar
  48. Ledo JH, Azevedo EP, Beckman D, Ribeiro FC, Santos LE, Razolli DS, Kincheski GC, Melo HM, Bellio M, Teixeira AL, Velloso LA, Foguel D, de Felice FG, Ferreira ST (2016) Cross talk between brain innate immunity and serotonin signaling underlies depressive-like behavior induced by Alzheimer’s amyloid-β oligomers in mice. J Neurosci 36:12106–12116CrossRefPubMedGoogle Scholar
  49. Ledo JH, Azevedo EP, Clarke JR, Ribeiro FC, Figueiredo CP, Foguel D, de Felice FG, Ferreira ST (2013) Amyloid-β oligomers link depressive-like behavior and cognitive deficits in mice. Mol Psychiatry 18:1053–1054CrossRefPubMedGoogle Scholar
  50. Lee CYD, Landreth GE (2010) The role of microglia in amyloid clearance from the AD brain. J Neural Transm 117:949–960CrossRefPubMedGoogle Scholar
  51. Lee SM, Yune TY, Kim SJ, Park DW, Lee YK, Kim YC, Oh YJ, Markelonis GJ, Oh TH (2003) Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma 20:1017–1027CrossRefPubMedGoogle Scholar
  52. Lichtenstein GR, Bala M, Han C, DeWoody K, Schaible T (2002) Infliximab improves quality of life in patients with Crohn’s disease. Inflamm Bowel Dis 8:237–243CrossRefPubMedGoogle Scholar
  53. Lin S, Wei X, Bales KR, Paul ABC, Ma Z, Yan G, Paul SM, du Y (2005) Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat. Eur J Neurosci 22:21–27CrossRefPubMedGoogle Scholar
  54. Loftis JM, Huckans M, Morasco BJ (2010) Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies. Neurobiol Dis 37:519–533CrossRefPubMedGoogle Scholar
  55. Lyketsos CG, Olin J (2002) Depression in Alzheimer’s disease: overview and treatment. Biol Psychiatry 52:243–252CrossRefPubMedGoogle Scholar
  56. Madrigal JLM, Hurtado O, Moro MA et al (2002) The increase in TNF-α levels is implicated in NF-κB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Neuropsychopharmacology 26:155–163CrossRefPubMedGoogle Scholar
  57. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M (2009) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24:27–53CrossRefPubMedGoogle Scholar
  58. Maier SF, Watkins LR (1995) Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res 695:279–282CrossRefPubMedGoogle Scholar
  59. Majidi J, Kosari-Nasab M, Salari A-A (2016) Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice. Brain Res Bull 120:1–13.  https://doi.org/10.1016/j.brainresbull.2015.10.009 CrossRefPubMedGoogle Scholar
  60. Mathias SD, Colwell HH, Miller DP, Moreland LW, Buatti M, Wanke L (2000) Health-related quality of life and functional status of patients with rheumatoid arthritis randomly assigned to receive etanercept or placebo. Clin Ther 22:128–139CrossRefPubMedGoogle Scholar
  61. Migliorelli R, Teson A, Sabe L, Petracchi M (1995) Prevalence and correlates of dysthymia and major depression among patients with Alzheimer’s disease. Am J Psychiatry 152:37CrossRefPubMedGoogle Scholar
  62. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Taki M, Ishihara K, Araki T, Horiguchi J (2012) Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study. Prog neuro-psychopharmacology Biol Psychiatry 37:222–226CrossRefGoogle Scholar
  63. Molina-Hernández M, Téllez-Alcántara NP, Pérez-García J, Olivera-Lopez JI, Jaramillo-Jaimes MT (2008) Desipramine or glutamate antagonists synergized the antidepressant-like actions of intra-nucleus accumbens infusions of minocycline in male Wistar rats. Prog Neuro-Psychopharmacology Biol Psychiatry 32:1660–1666CrossRefGoogle Scholar
  64. O’connor JC, Lawson MA, Andre C et al (2009) Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2, 3-dioxygenase activation in mice. Mol Psychiatry 14:511–522CrossRefPubMedGoogle Scholar
  65. O’Connor KA, Johnson JD, Hansen MK et al (2003) Peripheral and central proinflammatory cytokine response to a severe acute stressor. Brain Res 991:123–132CrossRefPubMedGoogle Scholar
  66. Olin JT, Katz IR, Meyers BS, Schneider LS, Lebowitz BD (2002a) Provisional diagnostic criteria for depression of Alzheimer disease: rationale and background. Am J Geriatr Psychiatry 10:129–141CrossRefPubMedGoogle Scholar
  67. Olin JT, Schneider LS, Katz IR, Meyers BS, Alexopoulos GS, Breitner JC, Bruce ML, Caine ED, Cummings JL, Devanand DP, Krishnan KRR, Lyketsos CG, Lyness JM, Rabins PV, Reynolds CF III, Rovner BW, Steffens DC, Tariot PN, Lebowitz BD (2002b) Provisional diagnostic criteria for depression of Alzheimer disease. Am J Geriatr Psychiatry 10:125–128CrossRefPubMedGoogle Scholar
  68. Paumier KL, Sortwell CE, Madhavan L, Terpstra B, Celano SL, Green JJ, Imus NM, Marckini N, Daley B, Steece-Collier K, Collier TJ (2015) Chronic amitriptyline treatment attenuates nigrostriatal degeneration and significantly alters trophic support in a rat model of parkinsonism. Neuropsychopharmacology 40:874–883CrossRefPubMedGoogle Scholar
  69. Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates. Academic Press, SixthGoogle Scholar
  70. Perry VH, Nicoll JAR, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6:193–201CrossRefPubMedGoogle Scholar
  71. Piirainen S, Youssef A, Song C et al (2017) Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer’s disease: the emerging role for microglia? Rev, Neurosci BiobehavGoogle Scholar
  72. Po KT, Siu AM-H, Lau BW-M, Chan JNM, So KF, Chan CCH (2015) Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results in depression-like behavior in rats. Exp Brain Res 233:2205–2214CrossRefPubMedGoogle Scholar
  73. Pugh CR, Nguyen KT, Gonyea JL et al (1999) Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation. Behav Brain Res 106:109–118CrossRefPubMedGoogle Scholar
  74. Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27:24–31CrossRefPubMedGoogle Scholar
  75. Reynolds JL, Ignatowski TA, Sud R, Spengler RN (2004) Brain-derived tumor necrosis factor-α and its involvement in noradrenergic neuron functioning involved in the mechanism of action of an antidepressant. J Pharmacol Exp Ther 310:1216–1225CrossRefPubMedGoogle Scholar
  76. Rosenberg PB, Martin BK, Frangakis C, Mintzer JE, Weintraub D, Porsteinsson AP, Schneider LS, Rabins PV, Munro CA, Meinert CL, Lyketsos CG, Drye LT (2010) Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry 18:136–145CrossRefPubMedPubMedCentralGoogle Scholar
  77. Salari A-A, Fatehi-Gharehlar L, Motayagheni N, Homberg JR (2016) Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring. Behav Brain Res 311:354–367.  https://doi.org/10.1016/j.bbr.2016.05.062 CrossRefPubMedGoogle Scholar
  78. Salari A-A, Samadi H, Homberg JR, Kosari-Nasab M (2018) Small litter size impairs spatial memory and increases anxiety-like behavior in a strain-dependent manner in male mice. Sci Rep 8Google Scholar
  79. Saravi SSS, Amirkhanloo R, Arefidoust A et al (2016a) On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system. Metab Brain Dis 31:549–561CrossRefGoogle Scholar
  80. Saravi SSS, Mousavi SE, Saravi SSS, Dehpour AR (2016b) Minocycline attenuates depressive-like behaviour induced by rat model of testicular torsion: involvement of nitric oxide pathway. Basic Clin Pharmacol Toxicol 118:249–258CrossRefPubMedGoogle Scholar
  81. Schiavone S, Tucci P, Mhillaj E, Bove M, Trabace L, Morgese MG (2017) Antidepressant drugs for beta amyloid-induced depression: a new standpoint? Prog Neuro-Psychopharmacology Biol Psychiatry 78:114–122CrossRefGoogle Scholar
  82. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608CrossRefPubMedPubMedCentralGoogle Scholar
  83. Simen BB, Duman CH, Simen AA, Duman RS (2006) TNFα signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol Psychiatry 59:775–785CrossRefPubMedGoogle Scholar
  84. Soczynska JK, Kennedy SH, Alsuwaidan M et al (2017) A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression. Bipolar Disord 19:198–213CrossRefPubMedGoogle Scholar
  85. Solati J, Salari AA (2011) Involvement of dorsal hippocampal NMDA-glutamatergic system in anxiety-related behaviors of rats. Neurochem J 5:5–199.  https://doi.org/10.1134/S1819712411030081 CrossRefGoogle Scholar
  86. Song X, Liu B, Cui L, Zhou B, Liu W, Xu F, Hayashi T, Hattori S, Ushiki-Kaku Y, Tashiro SI, Ikejima T (2017) Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiol Behav 179:487–493CrossRefPubMedGoogle Scholar
  87. Souza LC, Jesse CR, Antunes MS, Ruff JR, de Oliveira Espinosa D, Gomes NS, Donato F, Giacomeli R, Boeira SP (2016) Indoleamine-2, 3-dioxygenase mediates neurobehavioral alterations induced by an intracerebroventricular injection of amyloid-β 1-42 peptide in mice. Brain Behav Immun 56:363–377CrossRefPubMedGoogle Scholar
  88. Souza LC, Jesse CR, Del Fabbro L et al (2017) Swimming exercise prevents behavioural disturbances induced by an intracerebroventricular injection of amyloid-β 1-42 peptide through modulation of cytokine/NF-kappaB pathway and indoleamine-2, 3-dioxygenase in mouse brain. Behav Brain Res 331:1–13CrossRefPubMedGoogle Scholar
  89. Starkstein SE, Jorge R, Mizrahi R, Robinson RG (2005) The construct of minor and major depression in Alzheimer’s disease. Am J Psychiatry 162:2086–2093CrossRefPubMedGoogle Scholar
  90. Suk K (2004) Minocycline suppresses hypoxic activation of rodent microglia in culture. Neurosci Lett 366:167–171CrossRefPubMedGoogle Scholar
  91. Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 68:930–941CrossRefPubMedGoogle Scholar
  92. Tang M, Lin W, Pan Y, Guan XT, Li YC (2016) Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression. Physiol Behav 161:166–173CrossRefPubMedGoogle Scholar
  93. Tikka T, Fiebich BL, Goldsteins G, Keinänen R, Koistinaho J (2001) Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 21:2580–2588CrossRefPubMedGoogle Scholar
  94. Tomás-Camardiel M, Rite I, Herrera AJ, de Pablos RM, Cano J, Machado A, Venero JL (2004) Minocycline reduces the lipopolysaccharide-induced inflammatory reaction, peroxynitrite-mediated nitration of proteins, disruption of the blood–brain barrier, and damage in the nigral dopaminergic system. Neurobiol Dis 16:190–201CrossRefPubMedGoogle Scholar
  95. Vilalta-Franch J, Garre-Olmo J, López-Pousa S, Turon-Estrada A, Lozano-Gallego M, Hernàndez-Ferràndiz M, Pericot-Nierga I, Feijóo-Lorza R (2006) Comparison of different clinical diagnostic criteria for depression in Alzheimer disease. Am J Geriatr Psychiatry 14:589–597CrossRefPubMedGoogle Scholar
  96. Vogt MA, Mallien AS, Pfeiffer N, Inta I, Gass P, Inta D (2016) Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice. Behav Brain Res 301:96–101CrossRefPubMedGoogle Scholar
  97. Wainwright SR, Workman JL, Tehrani A, Hamson DK, Chow C, Lieblich SE, Galea LAM (2016) Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress. Horm Behav 79:58–69CrossRefPubMedGoogle Scholar
  98. Wang D, Lin W, Pan Y, Kuang X, Qi X, Sun H (2011) Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats. Brain Behav Immun 25:706–714CrossRefPubMedGoogle Scholar
  99. Wang H-T, Huang F-L, Hu Z-L, Zhang WJ, Qiao XQ, Huang YQ, Dai RP, Li F, Li CQ (2017) 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 31:505–520CrossRefPubMedGoogle Scholar
  100. Weintraub D, Rosenberg PB, Martin BK, Frangakis C, Mintzer JE, Porsteinsson AP, Schneider LS, Munro CA, Meinert CL, Lyketsos CG, Drye LT, Rabins PV (2010) Sertraline for the treatment of depression in Alzheimer disease: week-24 outcomes. Am J Geriatr Psychiatry 18:332–340CrossRefPubMedPubMedCentralGoogle Scholar
  101. Wortmann M (2012) Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther 4:40PubMedPubMedCentralGoogle Scholar
  102. Yang S-J, Yu H-Y, Kang D-Y, Ma ZQ, Qu R, Fu Q, Ma SP (2014) Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats. Pharmacol Biochem Behav 124:451–457CrossRefPubMedGoogle Scholar
  103. Yirmiya R, Rimmerman N, Reshef R (2015) Depression as a microglial disease. Trends Neurosci 38:637–658CrossRefPubMedGoogle Scholar
  104. Yrjänheikki J, Tikka T, Keinänen R et al (1999) A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci 96:13496–13500CrossRefPubMedGoogle Scholar
  105. Zeng Q, Wang S, Lim G, Yang L, Mao J, Sung B, Chang Y, Lim JA, Guo G, Mao J (2008) Exacerbated mechanical allodynia in rats with depression-like behavior. Brain Res 1200:27–38CrossRefPubMedGoogle Scholar
  106. Zhang XH, Jia N, Zhao XY, Tang GK, Guan LX, Wang D, Sun HL, Li H, Zhu ZL (2013a) Involvement of pGluR1, EAAT2 and EAAT3 in offspring depression induced by prenatal stress. Neuroscience 250:333–341CrossRefPubMedGoogle Scholar
  107. Zhang Y-Y, Fan Y-C, Wang M et al (2013b) Atorvastatin attenuates the production of IL-1β, IL-6, and TNF-α in the hippocampus of an amyloid β1-42-induced rat model of Alzheimer’s disease. Clin Interv Aging 8:103PubMedPubMedCentralGoogle Scholar
  108. Zheng L-S, Kaneko N, Sawamoto K (2015) Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice. Front Cell Neurosci 9:Google Scholar
  109. Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM (2011) Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuro-Psychopharmacology Biol Psychiatry 35:722–729CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physiology, School of MedicineArdabil University of Medical SciencesArdabilIran
  2. 2.Department of Anatomy and NeurobiologyUniversity of CaliforniaIrvineUSA
  3. 3.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Salari Institute of Cognitive and Behavioral Disorders (SICBD)AlborzIran

Personalised recommendations