Abstract
Neurodegeneration and depression are two common co-morbid conditions, particularly within the aging population. Research has linked neuroinflammation as a major contributing factor to both of these diseases. The key to neuroinflammation effects on neurodegeneration and depression appears to lie within the dysregulation of the control and release of pro- and anti-inflammatory cytokines. This can come from an internal or external insult to the system, or from changes in the individual due to aging that culminate in immune dysregulation. The need to reduce neuroinflammation has led to extensive research into neuroprotectants. We discuss the efficacy found with nicotine, alcohol, resveratrol, curcumin, and ketamine. Our main focus will be on what research tells us about the connections between neuroinflammation, neurodegeneration, and depression, and the hope that neuroprotectants research gives people suffering from neurodegeneration and depression stemming from neuroinflammation. We will conclude by making suggestions for future research in this area.
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References
Abe Y, Hashimoto S, Horie T (1999) Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 39:41–47
Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59
Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75
Allard JS, Tizabi Y, Shaffery JP, Trouth CO, Manaye K (2004) Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression. Neuropeptides 38:311–315
Aloisi F (2001) Immune function of microglia. Glia 36:165–179
Arora V, Kuhad A, Tiwari V, Chopra K (2011) Curcumin ameliorates reserpine-induced pain-depression dyad: behavioural, biochemical, neurochemical and molecular evidences. Psychoneuroendocrinology 36:1570–1581
Banasr M, Duman RS (2008) Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 64:863–870
Baron JA (1996) Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious. Br Med Bull 52:58–73
Barrientos RM, Higgins EA, Sprunger DB, Watkins LR, Rudy JW, Maier SF (2002) Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus. Behav Brain Res 134:291–298
Barrientos RM, Frank MG, Watkins LR, Maier SF (2010) Memory impairments in healthy aging: role of aging-induced microglial sensitization. Aging Dis 1:212–231
Barton BE (1997) IL-6: insights into novel biological activities. Clin Immunol Immunopathol 85:16–20
Barton BE, Shortall J, Jackson JV (1996) Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model. Infect Immun 64:714–718
Baumann RJ, Jameson HD, McKean HE, Haack DG, Weisberg LM (1980) Cigarette smoking and Parkinson disease: 1. Comparison of cases with matched neighbors. Neurology 30:839–843
Belmadani A, Zou JY, Schipma MJ, Neafsey EJ, Collins MA (2001) Ethanol pre-exposure suppresses HIV-1 glycoprotein 120-induced neuronal degeneration by abrogating endogenous glutamate/Ca2+-mediated neurotoxicity. Neuroscience 104:769–781
Belmadani A, Kumar S, Schipma M, Collins MA, Neafsey EJ (2004) Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning. NeuroReport 15:2093–2096
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354
Bhutani MK, Bishnoi M, Kulkarni SK (2009) Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav 92:39–43
Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69
Borrelli B, Niaura R, Keuthen NJ, Goldstein MG, DePue JD, Murphy C, Abrams DB (1996) Development of major depressive disorder during smoking-cessation treatment. J Clin Psychiatry 57:534–538
Bradamante S, Barenghi L, Villa A (2004) Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 22:169–188
Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002) Tumor necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Gut 51:37–43
Buckingham SD, Jones AK, Brown LA, Sattelle DB (2009) Nicotinic acetylcholine receptor signaling: roles in Alzheimer’s disease and amyloid neuroprotection. Pharmacol Rev 61:39–61
Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, Shakibaei M (2011) Curcumin modulates nuclear factor kappaB (NF-kappaB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem 286:28556–28566
Burgut FT, Benaur M, Hencliffe C (2006) Late-life depression: a neuropsychiatric approach. Expert Rev Neurother 6:65–72
Capuron L, Miller AH (2004) Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 56:819–824
Cebere A, Liljequist S (2003) Ethanol differentially inhibits homoquinolinic acid- and NMDA-induced neurotoxicity in primary cultures of cerebellar granule cells. Neurochem Res 28:1193–1199
Chandler LJ, Sumners C, Crews FT (1993) Ethanol inhibits NMDA receptor-mediated excitotoxicity in rat primary neuronal cultures. Alcohol Clin Exp Res 17:54–60
Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, Ganguli M (2001) Incidence of Alzheimer’s disease in a rural community in India: the Indo-US study. Neurology 57:985–989
Chang Y, Lee JJ, Hsieh CY, Hsiao G, Chou DS, Sheu JR (2009) Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation. Mediators Inflamm 2009:705379
Chatterjee PK, Yeboah MM, Dowling O, Xue X, Powell SR, Al-Abed Y, Metz CN (2012) Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in mice by suppressing inflammation and proteasome activity. PLoS ONE 7:e35361
Chen LW, Wang YQ, Wei LC, Shi M, Chan YS (2007) Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson’s disease. CNS Neurol Disord: Drug Targets 6:273–281
Chin Y, Brown DO, Taylor RE, Tizabi Y (2012) Protective effects of low dose alcohol concentrations against inflammatory-mediated toxicity in neuroblastoma-derived cells. Society for Neuroscience Annual Meeting, 866.09
Collins MA, Neafsey EJ, Zou JY (2000) HIV-I gpI20 neurotoxicity in brain cultures is prevented by moderate ethanol pretreatment. NeuroReport 11:1219–1222
Collins MA, Neafsey EJ, Mukamal KJ, Gray MO, Parks DA, Das DK, Korthuis RJ (2009) Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies. Alcohol Clin Exp Res 33:206–219
Collins MA, Neafsey EJ, Wang K, Achille NJ, Mitchell RM, Sivaswamy S (2010) Moderate ethanol preconditioning of rat brain cultures engenders neuroprotection against dementia-inducing neuroinflammatory proteins: possible signaling mechanisms. Mol Neurobiol 41:420–425
Conway CR, Sheline YI, Chibnall JT, Bucholz RD, Price JL, Gangwani S, Mintun MA (2012) Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder. Brain Stimul 5:163–171
Cook JW, Spring B, McChargue D (2007) Influence of nicotine on positive affect in anhedonic smokers. Psychopharmacology 192:87–95
Copeland RL Jr, Leggett YA, Kanaan YM, Taylor RE, Tizabi Y (2005) Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: implications for Parkinson’s disease. Neurotox Res 8:289–293
Copeland RL Jr, Das JR, Kanaan YM, Taylor RE, Tizabi Y (2007) Antiapoptotic effects of nicotine in its protection against salsolinol-induced cytotoxicity. Neurotox Res 12:61–69
Cotter D, Mackay D, Landau S, Kerwin R, Everall I (2001) Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 58:545–553
Covey LS, Glassman AH, Stetner F (1997) Major depression following smoking cessation. Am J Psychiatry 154:263–265
Csaki C, Mobasheri A, Shakibaei M (2009) Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthr Res Ther 11:R165
Cui WY, Li MD (2010) Nicotinic modulation of innate immune pathways via alpha7 nicotinic acetylcholine receptor. J Neuroimmune Pharmacol 5:479–488
Czeh B, Lucassen PJ (2007) What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci 257:250–260
Dajas-Bailador FA, Soliakov L, Wonnacott S (2002) Nicotine activates the extracellular signal-regulated kinase 1/2 via the alpha7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones. J Neurochem 80:520–530
Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ (2012) Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 21(8):1123–1140
Das JR, Tizabi Y (2009) Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res 16:194–204
de Souza MB, de Lemos RR, da Cunha JE, de Lima Filho JL, de Oliveira JR (2010) Searching for new genetic risk factors for neuropsychiatric disorders in expression databases. J Mol Neurosci 41:193–197
De R, Kundu P, Swarnakar S, Ramamurthy T, Chowdhury A, Nair GB, Mukhopadhyay AK (2009) Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrob Agents Chemother 53:1592–1597
Dinarello CA (1997) Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 11:91–103
Dinarello CA (1998) Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 16:457–499
Dixit AR, Crum RM (2000) Prospective study of depression and the risk of heavy alcohol use in women. Am J Psychiatry 157:751–758
Djuric VJ, Dunn E, Overstreet DH, Dragomir A, Steiner M (1999) Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines. Physiol Behav 67:533–537
Donnelly-Roberts DL, Xue IC, Arneric SP, Sullivan JP (1996) In vitro neuroprotective properties of the novel cholinergic channel activator (ChCA), ABT-418. Brain Res 719:36–44
Dorn HF (1959) Tobacco consumption and mortality from cancer and other diseases. Public Health Rep 74:581–593
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457
Edwards AC, Kendler KS (2011) Nicotine withdrawal-induced negative affect is a function of nicotine dependence and not liability to depression or anxiety. Nicotine Tob Res 13:677–685
Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A (2009) Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ 16:966–975
Fritze F, Ehrt U, Hortobagyi T, Ballard C, Aarsland D (2011) Depressive symptoms in Alzheimer’s disease and Lewy body dementia: a one-year follow-up study. Dement Geriatr Cogn Disord 32:143–149
Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29:357–365
Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC (2002) Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines. J Neurosci 22:6114–6120
Gemma C, Bachstetter AD, Bickford PC (2010) Neuron-microglia dialogue and hippocampal neurogenesis in the aged brain. Aging Dis 1:232–244
Getachew B, Hauser SR, Taylor RE, Tizabi Y (2008) Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains. Pharmacol Biochem Behav 91:97–103
Getachew B, Hauser SR, Taylor RE, Tizabi Y (2010) Alcohol-induced depressive-like behavior is associated with cortical norepinephrine reduction. Pharmacol Biochem Behav 96:395–401
Glassman AH, Covey LS, Stetner F, Rivelli S (2001) Smoking cessation and the course of major depression: a follow-up study. Lancet 357:1929–1932
Godbout JP, Johnson RW (2004) Interleukin-6 in the aging brain. J Neuroimmunol 147:141–144
Gold SM, Irwin MR (2009) Depression and immunity: inflammation and depressive symptoms in multiple sclerosis. Immunol Allergy Clin North Am 29:309–320
Gomez-Esteban JC, Tijero B, Somme J, Bilbao I, Fernandez J, Boyero S, Velasco F, Lezcano E, Zarranz JJ (2009) Application of depression criteria (DSM-IV) in patients with Parkinson’s disease. Clin Neurol Neurosurg 111:665–669
Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R (2008) Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13:717–728
Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL III, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611–7615
Guan ZZ, Yu WF, Nordberg A (2003) Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 43:243–249
Harada N, Zhao J, Kurihara H, Nakagata N, Okajima K (2011) Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus. J Nutr Biochem 22:1150–1159
Harrison NL, Simmonds MA (1985) Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol 84:381–391
Hauser SR, Getachew B, Taylor RE, Tizabi Y (2011) Alcohol induced depressive-like behavior is associated with a reduction in hippocampal BDNF. Pharmacol Biochem Behav 100:253–258
Hayley S, Poulter MO, Merali Z, Anisman H (2005) The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 135:659–678
Hejmadi MV, Dajas-Bailador F, Barns SM, Jones B, Wonnacott S (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci 24:779–786
Helmer KS, Cui Y, Chang L, Dewan A, Mercer DW (2003a) Effects of ketamine/xylazine on expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia. Shock 20:63–69
Helmer KS, Cui Y, Dewan A, Mercer DW (2003b) Ketamine/xylazine attenuates LPS-induced iNOS expression in various rat tissues. J Surg Res 112:70–78
Hemmerle AM, Herman JP, Seroogy KB (2012) Stress, depression and Parkinson’s disease. Exp Neurol 233:79–86
Hodgins DC, el-Guebaly N, Armstrong S (1995) Prospective and retrospective reports of mood states before relapse to substance use. J Consult Clin Psychol 63:400–407
Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186
Hurley LL, Akinfiresoye L, Tizabi Y (2012a) Behavioral and neurotrophic effects of curcumin in a putative animal model of depression. Society for Neuroscience Annual Meeting
Hurley LL, Taylor RE, Tizabi Y (2012b) Positive and negative effects of alcohol and nicotine and their interactions: a mechanistic review. Neurotox Res 21:57–69
Hurst SM, Wilkinson TS, McLoughlin RM, Jones S, Horiuchi S, Yamamoto N, Rose-John S, Fuller GM, Topley N, Jones SA (2001) Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 14:705–714
Ishikawa I, Kitamura H, Kimura K, Saito M (2001) Brain interleukin-1 is involved in blood interleukin-6 response to immobilization stress in rats. Jpn J Vet Res 49:19–25
Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220
Jarosik J, Legutko B, Unsicker K, von Bohlen Und Halbach O (2007) Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy. Exp Neurol 204:20–28
Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14:141–153
Kalejaiye O, Cortez L, Taylor RE, Tizabi Y (2011) Effects of Alcohol and Nicotine Combination in a Rat Model of Depression. Society for Neuroscience Annual Meeting, 794.08
Kalejaiye OO, Hurley LL, Taylor RE, Tizabi Y (2012) Nicotine mitigates depressogenic effects of alcohol in Wistar rats. Society for Neuroscience Annual Meeting, 665.03
Kasai T, Inada K, Takakuwa T, Yamada Y, Inoue Y, Shimamura T, Taniguchi S, Sato S, Wakabayashi G, Endo S (1997) Anti-inflammatory cytokine levels in patients with septic shock. Res Commun Mol Pathol Pharmacol 98:34–42
Kaster MP, Gadotti VM, Calixto JB, Santos AR, Rodrigues AL (2012) Depressive-like behavior induced by tumor necrosis factor-alpha in mice. Neuropharmacology 62:419–426
Kent S, Bluthe RM, Kelley KW, Dantzer R (1992) Sickness behavior as a new target for drug development. Trends Pharmacol Sci 13:24–28
Khairova RA, Machado-Vieira R, Du J, Manji HK (2009) A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 12:561–578
Kihara T, Shimohama S, Urushitani M, Sawada H, Kimura J, Kume T, Maeda T, Akaike A (1998) Stimulation of alpha4beta2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity. Brain Res 792:331–334
Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A (2001) Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem 276:13541–13546
Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H (1983) Antihepatotoxic principles of Curcuma longa Rhizomes1. Planta Med 49:185–187
Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105:751–756
Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M (2011) In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 35:744–759
Kulisevsky J, Pagonabarraga J, Pascual-Sedano B, Gironell A, Garcia-Sanchez C, Martinez-Corral M (2008) Motor changes during sertraline treatment in depressed patients with Parkinson’s disease*. Eur J Neurol 15:953–959
Kulkarni SK, Bhutani MK, Bishnoi M (2008) Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 201:435–442
Lakhan SE, Kirchgessner A (2011) Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med 9:129
Lavretsky H, Zheng L, Weiner MW, Mungas D, Reed B, Kramer JH, Jagust W, Chui H, Mack WJ (2008) The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. Int J Geriatr Psychiatry 23:1040–1050
Leonard BE (2007) Inflammation, depression and dementia: are they connected? Neurochem Res 32:1749–1756
Leonard BE, Myint A (2006) Inflammation and depression: is there a causal connection with dementia? Neurotox Res 10(2):149–160
Leonard BE, Myint A (2009) The psychoneuroimmunology of depression. Hum Psychopharmacol 24:165–175
Li S, Wang C, Wang M, Li W, Matsumoto K, Tang Y (2007) Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci 80:1373–1381
Libert C, Takahashi N, Cauwels A, Brouckaert P, Bluethmann H, Fiers W (1994) Response of interleukin-6-deficient mice to tumor necrosis factor-induced metabolic changes and lethality. Eur J Immunol 24:2237–2242
Liu Q, Zhao B (2004) Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures. Br J Pharmacol 141:746–754
Liu Y, Hu J, Wu J, Zhu C, Hui Y, Han Y, Huang Z, Ellsworth K, Fan W (2012) Alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte activation. J Neuroinflammation 9:98
Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501
Lynch MA (1998) Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta? Prog Neurobiol 56:571–589
Lynch MA (2002) Interleukin-1 beta exerts a myriad of effects in the brain and in particular in the hippocampus: analysis of some of these actions. Vitam Horm 64:185–219
Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63:349–352
Maes M (1993) A review on the acute phase response in major depression. Rev Neurosci 4:407–416
Maes M (1994) Cytokines in major depression. Biol Psychiatry 36:498–499
Maes M (1995) Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 19:11–38
Maes M (1999) Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461:25–46
Maes M (2001) The immunoregulatory effects of antidepressants. Hum Psychopharmacol 16:95–103
Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J (1990) Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 24:115–120
Maes M, Meltzer HY, Scharpe S, Cooreman W, Uyttenbroeck W, Suy E, Vandervorst C, Calabrese J, Raus J, Cosyns P (1993) Psychomotor retardation, anorexia, weight loss, sleep disturbances, and loss of energy: psychopathological correlates of hyperhaptoglobinemia during major depression. Psychiatry Res 47:229–241
Maes M, Smith R, Scharpe S (1995) The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 20:111–116
Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpe S, Smith RS (1998) The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 10:313–318
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 24:27–53
Manaye KF, Lei DL, Tizabi Y, Davila-Garcia MI, Mouton PR, Kelly PH (2005) Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J Neuropathol Exp Neurol 64:224–229
Manji HK, Duman RS (2001) Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull 35:5–49
McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED (2006) Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology 189:125–133
McEwen BS (2008) Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583:174–185
McKernan DP, Dinan TG, Cryan JF (2009) “Killing the Blues”: a role for cellular suicide (apoptosis) in depression and the antidepressant response? Prog Neurobiol 88:246–263
Moreno-Coutino A, Calderon-Ezquerro C, Drucker-Colin R (2007) Long-term changes in sleep and depressive symptoms of smokers in abstinence. Nicotine Tob Res 9:389–396
Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM (1991) Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88:1747–1754
Munoz P, Huenchuguala S, Paris I, Cuevas C, Villa M, Caviedes P, Segura-Aguilar J, Tizabi Y (2012) Protective effects of nicotine against aminochrome-induced toxicity in substantia nigra derived cells: implications for Parkinson’s Disease. Neurotox Res 22:177–180
Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 60:277–290
Nefzger MD, Quadfasel FA, Karl VC (1968) A retrospective study of smoking in Parkinson’s disease. Am J Epidemiol 88:149–158
Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH (2006) Curry consumption and cognitive function in the elderly. Am J Epidemiol 164:898–906
Nguyen KT, Deak T, Owens SM, Kohno T, Fleshner M, Watkins LR, Maier SF (1998) Exposure to acute stress induces brain interleukin-1beta protein in the rat. J Neurosci 18:2239–2246
O’Sullivan JB, Ryan KM, Curtin NM, Harkin A, Connor TJ (2009) Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: implications for depression and neurodegeneration. Int J Neuropsychopharmacol 12:687–699
Park HJ, Lee PH, Ahn YW, Choi YJ, Lee G, Lee DY, Chung ES, Jin BK (2007) Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. Eur J Neurosci 26:79–89
Parrott AC (2003) Cigarette-derived nicotine is not a medicine. World J Biol Psychiatry 4:49–55
Patel HC, Ross FM, Heenan LE, Davies RE, Rothwell NJ, Allan SM (2006) Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity. J Neurosci Res 83:385–391
Paulsen JS, Nehl C, Hoth KF, Kanz JE, Benjamin M, Conybeare R, McDowell B, Turner B (2005) Depression and stages of Huntington’s disease. J Neuropsychiatry Clin Neurosci 17:496–502
Perlis RH, Smoller JW, Mysore J, Sun M, Gillis T, Purcell S, Rietschel M, Nothen MM, Witt S, Maier W, Iosifescu DV, Sullivan P, Rush AJ, Fava M, Breiter H, Macdonald M, Gusella J (2010) Prevalence of incompletely penetrant Huntington’s disease alleles among individuals with major depressive disorder. Am J Psychiatry 167:574–579
Philip NS, Carpenter LL, Tyrka AR, Price LH (2010) Nicotinic acetylcholine receptors and depression: a review of the preclinical and clinical literature. Psychopharmacology 212:1–12
Philip NS, Carpenter LL, Tyrka AR, Price LH (2012) The nicotinic acetylcholine receptor as a target for antidepressant drug development. Sci World J 2012:104105
Piao WH, Campagnolo D, Dayao C, Lukas RJ, Wu J, Shi FD (2009) Nicotine and inflammatory neurological disorders. Acta Pharmacol Sin 30:715–722
Picciotto MR, Zoli M (2008) Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Front Biosci 13:492–504
Pollak Y, Yirmiya R (2002) Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 5:389–399
Pomerleau CS, Pomerleau OF (1992) Euphoriant effects of nicotine in smokers. Psychopharmacology 108:460–465
Pugh CR, Nguyen KT, Gonyea JL, Fleshner M, Wakins LR, Maier SF, Rudy JW (1999) Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation. Behav Brain Res 106:109–118
Pugh CR, Fleshner M, Watkins LR, Maier SF, Rudy JW (2001) The immune system and memory consolidation: a role for the cytokine IL-1beta. Neurosci Biobehav Rev 25:29–41
Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462
Quik M, Parameswaran N, McCallum SE, Bordia T, Bao S, McCormack A, Kim A, Tyndale RF, Langston JW, Di Monte DA (2006) Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates. J Neurochem 98:1866–1875
Quik M, Huang LZ, Parameswaran N, Bordia T, Campos C, Perez XA (2009) Multiple roles for nicotine in Parkinson’s disease. Biochem Pharmacol 78:677–685
Raison CL, Capuron L, Miller AH (2006) Cytokines sings the blues: inflammation and the pathogenesis of depression. Trends Immunol 27:24–31
Rajkowska G (2002) Cell pathology in mood disorders. Semin Clin Neuropsychiatry 7:281–292
Ramlochansingh C, Taylor RE, Tizabi Y (2011) Toxic effects of low alcohol and nicotine combinations in SH-SY5Y cells are apoptotically mediated. Neurotox Res 20:263–269
Raskind MA (2008) Diagnosis and treatment of depression comorbid with neurologic disorders. Am J Med 121:S28–S37
Ratsma JE, Van Der Stelt O, Gunning WB (2002) Neurochemical markers of alcoholism vulnerability in humans. Alcohol Alcohol 37:522–533
Ren K, Puig V, Papke RL, Itoh Y, Hughes JA, Meyer EM (2005) Multiple calcium channels and kinases mediate alpha7 nicotinic receptor neuroprotection in PC12 cells. J Neurochem 94:926–933
Ribeiro PO, Valentim AM, Rodrigues P, Olsson IA, Antunes LM (2012) Apoptotic neurodegeneration and spatial memory are not affected by sedative and anaesthetics doses of ketamine/medetomidine combinations in adult mice. Br J Anaesth 108:807–814
Rizvi SJ, Donovan M, Giacobbe P, Placenza F, Rotzinger S, Kennedy SH (2011) Neurostimulation therapies for treatment resistant depression: a focus on vagus nerve stimulation and deep brain stimulation. Int Rev Psychiatry 23:424–436
Rodgers B, Korten AE, Jorm AF, Jacomb PA, Christensen H, Henderson AS (2000) Non-linear relationships in associations of depression and anxiety with alcohol use. Psychol Med 30:421–432
Ross GW, Petrovitch H (2001) Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson’s disease. Drugs Aging 18:797–806
Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA (2005) Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry 57:21–26
Roubenoff R, Harris TB, Abad LW, Wilson PW, Dallal GE, Dinarello CA (1998) Monocyte cytokine production in an elderly population: effect of age and inflammation. J Gerontol A Biol Sci Med Sci 53:M20–M26
Rozas I (2009) Improving antidepressant drugs: update on recently patented compounds. Expert Opin Ther Pat 19:827–845
Rubio-Perez JM, Morillas-Ruiz JM (2012) A review: inflammatory process in Alzheimer’s disease, role of cytokines. Scien World J 2012:756357
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94:79–83
Salin-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colin R (1995) Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacology 121:476–479
Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB, Sung B, Sethi G, Aggarwal BB (2007a) Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med 43:568–580
Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, Limtrakul P, Badmaev V, Aggarwal BB (2007b) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 28:1765–1773
Sapolsky RM (2004) Is impaired neurogenesis relevant to the affective symptoms of depression? Biol Psychiatry 56:137–139
Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29:201–217
Schifilliti D, Grasso G, Conti A, Fodale V (2010) Anaesthetic-related neuroprotection: intravenous or inhalational agents? CNS Drugs 24:893–907
Schulteis G, Markou A, Cole M, Koob GF (1995) Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA 92:5880–5884
Semba J, Mataki C, Yamada S, Nankai M, Toru M (1998) Antidepressant like effects of chronic nicotine on learned helplessness paradigm in rats. Biol Psychiatry 43:389–391
Shapira-Lichter I, Beilin B, Ofek K, Bessler H, Gruberger M, Shavit Y, Seror D, Grinevich G, Posner E, Reichenberg A, Soreq H, Yirmiya R (2008) Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory. Brain Behav Immun 22:388–398
Sharma OP (1976) Antioxidant activity of curcumin and related compounds. Biochem Pharmacol 25:1811–1812
Sheline YI, Gado MH, Price JL (1998) Amygdala core nuclei volumes are decreased in recurrent major depression. NeuroReport 9:2023–2028
Sheline YI, Gado MH, Kraemer HC (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160:1516–1518
Shi FD, Piao WH, Kuo YP, Campagnolo DI, Vollmer TL, Lukas RJ (2009) Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol 182:1730–1739
Simuni T, Sethi K (2008) Nonmotor manifestations of Parkinson’s disease. Ann Neurol 64(Suppl 2):S65–S80
Singh R, Sharma P (2011) Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male Wistar rats. Toxicol Int 18:124–129
Singla N, Dhawan DK (2012) N-methyl N-nitrosourea induced functional and structural alterations in mice brain-role of curcumin. Neurotox Res 22(2):115–126
Sinha K, Chaudhary G, Gupta YK (2002) Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci 71:655–665
Sivaswamy S, Neafsey EJ, Collins MA (2010) Neuroprotective preconditioning of rat brain cultures with ethanol: potential transduction by PKC isoforms and focal adhesion kinase upstream of increases in effector heat shock proteins. Eur J Neurosci 32:1800–1812
Song C, Wang H (2011) Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 35:760–768
Soriano SG, Liu Q, Li J, Liu JR, Han XH, Kanter JL, Bajic D, Ibla JC (2010) Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain. Anesthesiology 112:1155–1163
Spak L, Spak F, Allebeck P (2000) Alcoholism and depression in a Swedish female population: co-morbidity and risk factors. Acta Psychiatr Scand 102:44–51
Spring B, Cook JW, Appelhans B, Maloney A, Richmond M, Vaughn J, Vanderveen J, Hedeker D (2008) Nicotine effects on affective response in depression-prone smokers. Psychopharmacology 196:461–471
Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285:E433–E437
Stella F, Banzato CE, Barasnevicius Quagliato EM, Viana MA (2008) Depression in patients with Parkinson’s disease: impact on functioning. J Neurol Sci 272:158–163
Steptoe A, Hamer M, Chida Y (2007) The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 21:901–912
Steuber TL, Danner F (2006) Adolescent smoking and depression: which comes first? Addict Behav 31:133–136
Stevens TR, Krueger SR, Fitzsimonds RM, Picciotto MR (2003) Neuroprotection by nicotine in mouse primary cortical cultures involves activation of calcineurin and L-type calcium channel inactivation. J Neurosci 23:10093–10099
Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58:233–247
Streit WJ, Xue QS (2010) The Brain’s aging immune system. Aging Dis 1:254–261
Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581
Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 68:930–941
Takahashi S, Mizukami K, Yasuno F, Asada T (2009) Depression associated with dementia with Lewy bodies (DLB) and the effect of somatotherapy. Psychogeriatrics 9:56–61
Taniguchi T, Shibata K, Yamamoto K (2001) Ketamine inhibits endotoxin-induced shock in rats. Anesthesiology 95:928–932
Taniguchi T, Kanakura H, Takemoto Y, Yamamoto K (2004) The antiinflammatory effects of ketamine in endotoxemic rats during moderate and mild hypothermia. Anesth Analg 98:1114–1120 (table of contents)
Teng E, Ringman JM, Ross LK, Mulnard RA, Dick MB, Bartzokis G, Davies HD, Galasko D, Hewett L, Mungas D, Reed BR, Schneider LS, Segal-Gidan F, Yaffe K, Cummings JL (2008) Diagnosing depression in Alzheimer disease with the national institute of mental health provisional criteria. Am J Geriatr Psychiatry 16:469–477
Thacker EL, O’Reilly EJ, Weisskopf MG, Chen H, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A (2007) Temporal relationship between cigarette smoking and risk of Parkinson disease. Neurology 68:764–768
Tizabi Y, Overstreet DH, Rezvani AH, Louis VA, Clark E Jr, Janowsky DS, Kling MA (1999) Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142:193–199
Tizabi Y, Rezvani AH, Russell LT, Tyler KY, Overstreet DH (2000) Depressive characteristics of FSL rats: involvement of central nicotinic receptors. Pharmacol Biochem Behav 66:73–77
Tizabi Y, Al-Namaeh M, Manaye KF, Taylor RE (2003) Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells. Neurotox Res 5:315–321
Tizabi Y, Manaye KF, Smoot DT, Taylor RE (2004) Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Neurotox Res 6:311–316
Tizabi Y, Manaye KF, Taylor RE (2005) Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells. Neurotox Res 7:319–322
Tizabi Y, Bhatti BH, Taylor RE (2009a) Antidepressant-like effects of low alcohol doses in an animal model of depression. Alc Clin Exp Res 33(Suppl):157A
Tizabi Y, Getachew B, Rezvani AH, Hauser SR, Overstreet DH (2009b) Antidepressant-like effects of nicotine and reduced nicotinic receptor binding in the Fawn-Hooded rat, an animal model of co-morbid depression and alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 33:398–402
Tizabi Y, Hauser SR, Tyler KY, Getachew B, Madani R, Sharma Y, Manaye KF (2010) Effects of nicotine on depressive-like behavior and hippocampal volume of female WKY rats. Prog Neuropsychopharmacol Biol Psychiatry 34:62–69
Tizabi Y, Bhatti BH, Manaye KF, Das JR, Akinfiresoye L (2012a) Antidepressant-like effects of low ketamine dose is associated with increased hippocampal AMPA/NMDA receptor density ratio in female Wistar–Kyoto rats. Neuroscience 213:72–80
Tizabi Y, Qualls Z, Brown DO, Chin Y, Hurley LL, Taylor RE (2012b) Neuroprotective effects of low alcohol concentration against LPS-induced toxicity in cultured cells. Alc Clin Exp Res 36(6):21A
Toth E, Gersner R, Wilf-Yarkoni A, Raizel H, Dar DE, Richter-Levin G, Levit O, Zangen A (2008) Age-dependent effects of chronic stress on brain plasticity and depressive behavior. J Neurochem 107:522–532
Tredici G, Miloso M, Nicolini G, Galbiati S, Cavaletti G, Bertelli A (1999) Resveratrol, map kinases and neuronal cells: might wine be a neuroprotectant? Drugs Exp Clin Res 25:99–103
Tsoh JY, Humfleet GL, Munoz RF, Reus VI, Hartz DT, Hall SM (2000) Development of major depression after treatment for smoking cessation. Am J Psychiatry 157:368–374
Tupala E, Tiihonen J (2004) Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry 28:1221–1247
Ulloa L (2005) The vagus nerve and the nicotinic anti-inflammatory pathway. Nat Rev Drug Discov 4:673–684
Upadhyaya HP, Deas D, Brady KT, Kruesi M (2002) Cigarette smoking and psychiatric comorbidity in children and adolescents. J Am Acad Child Adolesc Psychiatry 41:1294–1305
Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296–300
Van der Schyf CJ (2011) The use of multi-target drugs in the treatment of neurodegenerative diseases. Expert Rev Clin Pharmacol 4:293–298
Vas CJ, Pinto C, Panikker D, Noronha S, Deshpande N, Kulkarni L, Sachdeva S (2001) Prevalence of dementia in an urban Indian population. Int Psychogeriatr 13:439–450
Venkatesan N, Punithavathi D, Arumugam V (2000) Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol 129:231–234
Vingtdeux V, Dreses-Werringloer U, Zhao H, Davies P, Marambaud P (2008) Therapeutic potential of resveratrol in Alzheimer’s disease. BMC Neurosci 9(Suppl 2):S6
Viviani B, Bartesaghi S, Corsini E, Galli CL, Marinovich M (2004) Cytokines role in neurodegenerative events. Toxicol Lett 149:85–89
Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM (2002) Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med 9:77–79
Wang Y, Lu Z, Wu H, Lv F (2009) Study on the antibiotic activity of microcapsule curcumin against foodborne pathogens. Int J Food Microbiol 136:71–74
Wegelius K, Korpi ER (1995) Ethanol inhibits NMDA-induced toxicity and trophism in cultured cerebellar granule cells. Acta Physiol Scand 154:25–34
Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition–the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 50:2041–2056
Wirleitner B, Neurauter G, Schrocksnadel K, Frick B, Fuchs D (2003) Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Curr Med Chem 10:1581–1591
Wuwongse S, Chang RC, Law AC (2010) The putative neurodegenerative links between depression and Alzheimer’s disease. Prog Neurobiol 91:362–375
Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, Achong MK (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101:311–320
Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005a) Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav 82:200–206
Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005b) The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol 518:40–46
Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA, Vernon MM, Du X, Li G, Pan J, Ogle WO (2010) Antidepressant-like effect of trans-resveratrol: involvement of serotonin and noradrenaline system. Eur Neuropsychopharmacol 20:405–413
Yamane Y, Sakai K, Maeda K (2011) Dementia with Lewy bodies is associated with higher scores on the Geriatric Depression Scale than is Alzheimer’s disease. Psychogeriatrics 11:157–165
Yilmaz A, Schulz D, Aksoy A, Canbeyli R (2002) Prolonged effect of an anesthetic dose of ketamine on behavioral despair. Pharmacol Biochem Behav 71:341–344
Yirmiya R, Barak O, Avitsur R, Gallily R, Weidenfeld J (1997) Intracerebral administration of Mycoplasma fermentans produces sickness behavior: role of prostaglandins. Brain Res 749:71–81
Yokoyama T, Miyazawa K, Naito M, Toyotake J, Tauchi T, Itoh M, Yuo A, Hayashi Y, Georgescu MM, Kondo Y, Kondo S, Ohyashiki K (2008) Vitamin K2 induces autophagy and apoptosis simultaneously in leukemia cells. Autophagy 4:629–640
Zarate CA Jr, Singh JB, Quiroz JA, De Jesus G, Denicoff KK, Luckenbaugh DA, Manji HK, Charney DS (2006) A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 163:153–155
Zec RF, Burkett NR (2008) Non-pharmacological and pharmacological treatment of the cognitive and behavioral symptoms of Alzheimer disease. NeuroRehabilitation 23:425–438
Zhang F, Wang H, Wu Q, Lu Y, Nie J, Xie X, Shi J (2012) Resveratrol protects cortical neurons against microglia-mediated neuroinflammation. Phytother Res. doi:10.1002/ptr.4734
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660
Zou JY, Crews FT (2005) TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 1034:11–24
Zou X, Patterson TA, Divine RL, Sadovova N, Zhang X, Hanig JP, Paule MG, Slikker W Jr, Wang C (2009) Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci 27:727–731
Zunszain PA, Hepgul N, Pariante CM (2012) Inflammation and depression. Curr Top Behav Neurosci. May 3 (epub ahead of print)
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This study was supported by NIH/NIGMS (2 SO6 GM08016-39) and NIH-RCMI 2 G12 RR003048.
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Hurley, L.L., Tizabi, Y. Neuroinflammation, Neurodegeneration, and Depression. Neurotox Res 23, 131–144 (2013). https://doi.org/10.1007/s12640-012-9348-1
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DOI: https://doi.org/10.1007/s12640-012-9348-1