Modulation of catalase, copper and zinc in the hippocampus and the prefrontal cortex in social isolation‑induced depression in male rats
Depression is a chronic illness of unknown etiology. Trace elements, such as copper and zinc, and defense antioxidants, such as catalase, are important factors that determine the clinical course of brain diseases. Furthermore, altered glucose metabolism in hippocampus and prefrontal cortex has been associated with depression. Identifying factors that can precipitate depressive-like behavior is of particular importance as it can direct clinicians towards the etiology of the disease. In this study, 16 male Sprague-Dawley rats were randomly divided into two groups: socialized and socially isolated. After one week of acclimatization, animals were housed in isolation for 14 days. Rats in the social group were socialized together for 14 days. On day 15, the forced swim test was performed and blood sugar was analyzed. The brain was removed immediately for biochemical analysis. Socially isolated rats showed more pronounced depressive-like behavior in the forced swim test than socialized rats. Moreover, socially isolated rats demonstrated significantly lower copper and zinc concentrations, as well as a marked reduction in catalase activity, in both prefrontal cortex and hippocampus compared to socialized rats. Additionally, blood sugar levels were higher in socially isolated animals. Isolation causes reduction in copper and zinc levels and catalase activity, which may precipitate depressive-like behavior in these animals.
- Andreoulakis E, Hyphantis T, Kandylis D, Iacovides A (2012) Depression in diabetes mellitus: a comprehensive review. Hippokratia 16: 205–214.
- Becker JS, Salber D (2010) New mass spectrometric tools in brain research. Trac-Trend Anal Chem 29: 966–979.
- Berk M, Ng F, Dean O, Dodd S, Bush AI (2008) Glutathione: a novel treatment target in psychiatry. Trends Pharmacol Sci 29: 346–351.
- Bertoni-Freddari C, Fattoretti P, Casoli T, Di Stefano G, Solazzi M, Perna E, De Angelis C (2006) Reactive structural dynamics of synaptic mitochondria in ischemic delayed neuronal death. Ann N Y Acad Sci 1090: 26–34.
- Bobilya DJ, Gauthier NA, Karki S, Olley BJ, Thomas WK (2008) Longitudinal changes in zinc transport kinetics, metallothionein and zinc transporter expression in a blood–brain barrier model in response to a moderately excessive zinc environment. J Nutr Biochem 19: 129–137.
- Brutman D, Mhlanga M (2013) Catalase overexpression rescues Friedreich’s Ataxia mouse models from oxidative stress and mitochondrial iron-loading. Eukaryon 9.
- Cacioppo JT, Hawkley LC, Ernst JM, Burleson M, Berntson GG, Nouriani B, Spiegel D (2006) Loneliness within a nomological net: An evolutionary perspective. J Res Personal 40: 1054–1085.
- Campbell S, MacQueen G (2004) The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 29: 417–426.
- Castagné V, Moser P, Roux S, Porsolt RD (2010) Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Prot Pharmacol: 5.8. 1–5.8. 14.
- Ceriello A, Dello Russo P, Amstad P, Cerutti P (1996) High glucose induces antioxidant enzymes in human endothelial cells in culture: evidence linking hyperglycemia and oxidative stress. Diabetes 45: 471–477.
- Choi H, Irwin MR, Cho HJ (2015) Impact of social isolation on behavioral health in elderly: Systematic review. World J Psychiatr 5: 432–438.
- Chowanadisai W, Kelleher SL, Lönnerdal B (2005) Zinc deficiency is associated with increased brain zinc import and LIV-1 expression and decreased ZnT-1 expression in neonatal rats. J Nutr 135: 1002–1007.
- Colvin RA, Davis N, Nipper RW, Carter PA (2000) Zinc transport in the brain: Routes of zinc influx and efflux in neurons. J Nutr 130: 1484S-1487S.
- De Jong Gierveld J, Havens B (2004) Cross-national comparisons of social isolation and loneliness: introduction and overview. Canadian Journal on Aging/La Revue canadienne du vieillissement 23: 109–113.
- Detka J, Kurek A, Kucharczyk M, Głombik K, Basta-Kaim A, Kubera M, Lasoń W, Budziszewska B (2015) Brain glucose metabolism in an animal model of depression. Neuroscience 295: 198–208.
- Doboszewska U, Wlaz P, Nowak G, Radziwon-Zaleska M, Cui RJ, Mlyniec K (2017) Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity. Neural Plast.
- Eby GA, Eby Kl (2006) Rapid recovery from major depression using magnesium treatment. Med Hypotheses 67: 362–370.
- Frederickson C, Danscher G (1990) Zinc-containing neurons in hippocampus and related CNS structures. Progress in brain research 83: 71–84.
- Frederickson CJ, Suh SW, Silva D, Frederickson CJ, Thompson RB (2000) Importance of zinc in the central nervous system: the zinc-containing neuron. J Nutr 130: 1471S-183S.
- Gawryluk JW, Wang JF, Andreazza AC, Shao L, Yatham LN, Young LT (2011) Prefrontal cortex glutathione S-transferase levels in patients with bipolar bipolar disorder, major depression and schizophrenia. Int J Neuropsychopharmacol 14: 1069–1074.
- Genet S, Kale RK, Baquer NZ (2002) Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonellafoenum graecum). Molecular and cellular biochemistry 236: 7–12.
- Habib SA, Saad EA, Elsharkawy AA, Attia ZR (2015) Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents. Advances Medical Sciences 60: 179–185.
- Hopt A, Korte S, Fink H, Panne U, Niessner R, Jahn R, Kretzchmar H, Herms J (2003) Methods for studying synaptosomal copper release. J Neurosci Meth 128: 159–172.
- Jin J, Maren S (2015) Prefrontal-Hippocampal Interactions in Memory and Emotion. Front Syst Neurosci 9: 170.
- Kapfhammer HP (2006) Somatic symptoms in depression. Dialogues in clinical neuroscience 8: 227.
- Kaut O, Schmitt I, Hofmann A, Hoffmann P, Schlaepfer TE, Wullner U, Hurlemann R (2015) Aberrant NMDA receptor DNA methylation detected by epigenome-wide analysis of hippocampus and prefrontal cortex in major depression. Eur Arch Psychiatry Clin Neurosci 265: 331–341.
- Kern S, Oakes TR, Stone CK, Mcauliff EM, Kirschbaum C, Davidson RJ (2008) Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor. Psychoneuroendocrinology 33: 517–529.
- Kodama M, Fujioka T, Duman RS (2004) Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry 56: 570–580.
- Li CT, Su TP, Wang SJ, Tu PC, Hsieh JC (2015) Prefrontal glucose metabolism in medication-resistant major depression. British J Psychiatry 206: 316–323.
- Ma Sh, Teasdale JD (2004) Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J Consulting Clinical Psychology 72: 31.
- Mao P, Manczak M, Calkins MJ, Truong Q, Reddy TP, Reddy AP, Shirendeb U, Lo HH, Rabinovitch PS, Reddy PH (2012) Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer’s disease: implications for neuroprotection and lifespan extension. Hum Mol Genet 21: 2973–90.
- Mcewen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54: 20–23.
- Menezes HS, Bueno BB, Ciulla L, Schuh A, Luz Fde F, Alves RJ, Abegg MP, Cirino SL (2008) Antidepressant behavioral effects of duloxetine and amitriptyline in the rat forced swimming test. Acta Cir Bras 23: 447–450.
- Meyer-Lindenberg A, Weinberger DR (2006) Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews Neuroscience 7: 818–827.
- Mlyniec K, Nowak G (2012) Zinc deficiency induces behavioral alterations in the tail suspension test in mice. Effect of antidepressants. Pharmacol Rep 64: 249–255.
- Mlyniec K, Ostachowicz B, Krakowska A, Reczynski W, Opoka W, Nowak G (2014) Chronic but not acute antidepressant treatment alters serum zinc/copper ratio under pathological/zinc-deficient conditions in mice. J Physiol Pharmacol 65: 673–678.
- Morgan D (2003) Mindfulness-based cognitive therapy for depression: A new approach to preventing relapse. Psychother Res 13: 123–125.
- Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B (2007) Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370: 851–858.
- Navarro-Alarcon M, Ruiz-Ojeda Fj, Blanca-Herrera Rm, Agil A (2013) Antioxidant activity of melatonin in diabetes in relation to the regulation and levels of plasma Cu, Zn, Fe, Mn, and Se in Zucker diabetic fatty rats. Nutrition 29: 785–789.
- Ni M, You Y, Chen J, Zhang L (2018) Copper in depressive disorder: a systematic review and meta-analysis of observational studies. Psychiatry Res 267: 506–515.
- O’Donnell P (2012) Cortical interneurons, immune factors and oxidative stress as early targets for schizophrenia. European j neurosci 35: 1866–1870.
- Omata N, Murata T, Maruoka N, Ikeda H, Mitsuya H, Mizuno T, Mita K, Asano M, Kiyono Y, Okazawa H (2012) Effect of dietary zinc deficiency on ischemic vulnerability of the brain. Neurosci Lett 531: 10–13.
- Raskind MA (2008) Diagnosis and treatment of depression comorbid with neurologic disorders. American j medicine 121: S28-S37.
- Robinson Nj, Winge DR (2010) Copper Metallochaperones. Annu Rev Biochem 79: 537–562.
- Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nature Neurosci 10: 1110.
- Scheiber IF, Mercer JF, Dringen R (2014) Metabolism and functions of copper in brain. Progress Neurobiol 116: 33–57.
- Sherbourne CD, Wells KB, Meredith LS, Jackson CA, Camp P (1996) Comorbid anxiety disorder and the functioning and well-being of chronically ill patients of general medical providers. Arch General Psychiatry 53: 889–895.
- Sullivan PF, Neale MC, Kendler KS (2000) Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 157: 1552–1562.
- Takeda A, Tamano H, Kan F, Itoh H, Oku N (2007) Anxiety-like behavior of young rats after 2-week zinc deprivation. Behav Brain Res 177: 1–6.
- Tanti A, Belzung C (2013) Neurogenesis along the septo-temporal axis of the hippocampus: are depression and the action of antidepressants region-specific? Neuroscience 252: 234–252.
- Tomaka J, Thompson S, Palacios R (2006) The relation of social isolation, loneliness, and social support to disease outcomes among the elderly. J Aging Health 18: 359–384.
- Vergun O, Dineley K, Reynolds I (2007) Ion Transport and Energy Metabolism. Handbook of Neurochemistry and Molecular Neurobiology. Springer.
- Vostrikov VM, Uranova NA, Orlovskaya DD (2007) Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. Schizophrenia research 94: 273–280.
- Waggoner DJ, Bartnikas TB, Gitlin JD (1999) The role of copper in neurodegenerative disease. Neurobiol Dis 6: 221–230.
- Webster M, Knable M, Johnston-Wilson N, Nagata K, Inagaki M, Yolken R (2001) Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. Brain Behav Immun 15: 388–400.
- Wengenack TM, Curran Gl, Olson EE, Poduslo JF (1997) Putrescine-modified catalase with preserved enzymatic activity exhibits increased permeability at the blood-nerve and blood-brain barriers. Brain Res 767: 128–135.
- Yang M, Wong M (2001) Changes in Ca, Cu, Fe, Mg, and Zn contents in mouse brain tissues after prolonged oral ingestion of brick tea liquor containing a high level of Al. Bio Trace Elem Res 80: 67–76.
- Zhou W, Wang N, Yang C, Li XM, Zhou ZQ, Yang JJ (2014) Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex. European Psychiatry 29: 419–423.