Neuroprotective Potential of Minocycline in Metabolic Syndrome-Induced Cognitive Impairment: An Experimental Study in Mice
DOI:
https://doi.org/10.69980/jaz.v37i01.5386Keywords:
Metabolic syndrome, cognitive impairment, minocycline, oxidative stress, neuroinflammation, hippocampusAbstract
Metabolic syndrome (MetS) is increasingly recognized as a risk factor for cognitive decline and neurodegenerative disorders. This study investigates the underlying mechanisms of MetS-induced cognitive impairment and evaluates the therapeutic potential of minocycline. MetS was induced in Swiss albino mice using a high-fat high-carbohydrate (HFHC) diet. Behavioral, biochemical, and histopathological assessments were conducted to evaluate cognitive function, oxidative stress, and neuroinflammation. MetS animals exhibited significant metabolic alterations, impaired memory, increased acetylcholinesterase activity, elevated inflammatory cytokines, and reduced antioxidant defenses. Minocycline treatment significantly improved cognitive performance, reduced oxidative stress, and attenuated inflammatory responses. Histological analysis confirmed neuroprotection in hippocampal regions. These findings suggest that minocycline may serve as a potential therapeutic agent for managing MetS-associated cognitive dysfunction.
Downloads
References
1. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome – A new worldwide definition. Lancet. 2005;366:1059–62.
2. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents – An IDF consensus report. Pediatr Diabetes. 2007;8:299–306.
3. Ravikiran M, Bhansali A, Ravikumar P, Bhansali S, Dutta P, Thakur JS, et al. Prevalence and risk factors of metabolic syndrome among Asian Indians: A community survey. Diabetes Res Clin Pract. 2010;89:181–8.
4. Nerkar D, Mukherjee A, Mehta BK, Banerjee S. Metabolic syndrome associated complications. Int J Pharm Pharm Sci. 2015;7:22–5.
5. Iadecola C, Yaffe K, Biller J, Bratzke LC, Faraci FM, Gorelick PB, et al. Impact of hypertension on cognitive function: A scientific statement from the American Heart Association. Hypertension. 2016;68:e67–94.
6. Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK, et al. Cognitive impairment following high-fat diet consumption is associated with brain inflammation. J Neuroimmunol. 2010;219:25–32.
7. Miller AA, Spencer SJ. Obesity and neuroinflammation: A pathway to cognitive impairment. Brain Behav Immun. 2014;42:10–21.
8. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Minocycline as adjunctive therapy for patients with unipolar psychotic depression: An open-label study. Prog Neuropsychopharmacol Biol Psychiatry. 2012;37:222–6.
9. Rodriguez CI, Bender J Jr, Marcus SM, Snape M, Rynn M, Simpson HB, et al. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: An open-label trial. J Clin Psychiatry. 2010;71:1247–9.
10. Burke NN, Kerr DM, Moriarty O, Finn DP, Roche M. Minocycline modulates neuropathic pain behaviour and cortical microglial gene expression in a rat model of depression. Brain Behav Immun. 2014;42:147–56.
11. Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, et al. Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation. Neurobiol Dis. 2007;25:514–25.
12. Majidi J, Kosari-Nasab M, Salari AA. 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. 2016;120:1–3.
13. Krady JK, Basu A, Allen CM, Xu Y, LaNoue KF, Gardner TW, et al. Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes. 2005;54:1559–65.
14. Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J, et al. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia. Proc Natl Acad Sci U S A. 1999;96:13496–500.
15. Akbaraly TN, Kivimaki M, Shipley MJ, Tabak AG, Jokela M, Virtanen M, et al. Metabolic syndrome over 10 years and cognitive functioning in late midlife. Diabetes Care. 2010;33:84–9.
16. Mukherjee A, Sen KK, Banerjee S. Effect of metabolic syndrome on depression in mice. Indian J Pharm Educ. 2018;52:S46–53.
17. Mukherjee D, Banerjee S. Learning and memory promoting effects of crude garlic extract. Indian J Exp Biol. 2013;51:1094–100.
18. Moron MS, Depierre JW, Mannervik B. Levels of glutathione and related enzymes in rat lung and liver. Biochim Biophys Acta. 1979;582:67–78.
19. Marsland AL, McCaffery JM, Muldoon MF, Manuck SB. Systemic inflammation and metabolic syndrome. Metabolism. 2010;59:1801–8.
20. Cancello R, Clément K. Is obesity an inflammatory illness? BJOG. 2006;113:1141–7.
21. Donath MY, Böni-Schnetzler M, Ellingsgaard H, Halban PA, Ehses JA. Cytokine production in diabetes. Trends Endocrinol Metab. 2010;21:261–7.
22. Schmidt MI, Duncan BB. Diabesity: An inflammatory metabolic condition. Clin Chem Lab Med. 2003;41:1120–30.
23. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to depression: Immune system effects on brain. Nat Rev Neurosci. 2008;9:46–56.
24. Dinel AL, André C, Aubert A, Ferreira G, Layé S, Castanon N, et al. Cognitive alterations linked to hippocampal inflammation in metabolic syndrome. PLoS One. 2011;6:e24325.
25. Barnham KJ, Masters CL, Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov. 2004;3:205–14.
26. Gancheva SM, Zhelyazkova-Savova MD. Vitamin K2 effects in metabolic syndrome. Folia Med (Plovdiv). 2016;58:264–72.
27. Johnson LA, Zuloaga KL, Kugelman TL, Mader KS, Morré JT, Zuloaga DG, et al. Improvement of cognitive impairment in metabolic syndrome. EBioMedicine. 2016;3:26–42.
28. Hein AM, O’Banion MK. Neuroinflammation and memory. Mol Neurobiol. 2009;40:15–32.
29. Silva Bastos LF, Pinheiro de Oliveira AC, Schlachetzki JC, Fiebich BL. Minocycline reduces prostaglandin synthesis in microglia. Immunopharmacol Immunotoxicol. 2011;33:576–80.
30. Iyer A, Lim J, Poudyal H, Reid RC, Suen JY, Webster J, et al. Phospholipase A2 inhibitor protects against metabolic syndrome. Diabetes. 2012;61:2320–9.
31. Taha AY, Gao F, Ramadan E, Cheon Y, Rapoport SI, Kim HW, et al. Brain lipid metabolism in metabolic syndrome. BMC Neurosci. 2012;13:131.
32. Garrido-Mesa N, Zarzuelo A, Gálvez J. Minocycline: Far beyond an antibiotic. Br J Pharmacol. 2013;169:337–52.
33. Mehta B, Banerjee S. Cognitive impairment in diabetic rats. Indian J Pharm Sci. 2017;79:785–93.
34. Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline inhibits microglial activation. J Neurosci. 2001;21:2580–8.
35. Cai Z, Zhao Y, Yao S, Zhao B. Minocycline reduces amyloid pathology via NF-κB inhibition. Pharmacol Rep. 2011;63:381–91.
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Amol Yadavrao Ghodke
This work is licensed under a Creative Commons Attribution 4.0 International License.
