Zataria multiflora could improve hippocampal tau protein and TNFα levels and cognitive behavior defects in a rat model of Alzheimer's disease

Document Type : Original Research Article

Authors

1 Physiology division of Basic Science Department, School of Vet Med; Shiraz University, Shiraz—Iran

2 Physiology division of Basic Science Department, School of Vet Med; Shiraz University, Shiraz, Iran.

3 Pharmacology division of Basic Science Department, School of Vet Med; Shiraz University, Shiraz—Iran

Abstract

Objective: Zataria multiflora (ZM) is a plant with ethnopharmacological value which was recently tested to reduce symptoms of Alzheimer’s disease (AD). The aim of the present study was to determine the effect of ZM essential oil on spatial cognitive and noncognitive behavior, as well as hippocampal tau protein and tumor necrosis factor alpha (TNFα) concentrations in rats with AD.
Materials and Methods: Thirty-five adult male Sprague Dawley rats (300±30 g) were randomly divided into 5 groups: control (intact rats); sham (received intracerebroventricular (ICV) microinjection of normal saline); AD control (rats with AD that did not receive any treatment); vehicle control (rats with AD that orally received tween-80, 5% (ZM essential oil vehicle) for 20 days) and experimental (rats with AD that orally received ZM essential oil 100 µl/kg/day for 20 days). AD was induced by bidirectional microinjection of β amyloid 1-42 (10 µg/2µl). Tau protein and TNFα concentrations were measured by ELISA methods. Spatial cognitive and noncognitive behavior were determined by Morris water maze (MWM) test.
Results: ZM essential oil significantly improved latency time, time spent in the target quarter and cognitive behavior of rats with AD compared to control and sham groups (p<0.05). Hippocampal tau protein and TNFα concentrations were significantly higher in both AD control and vehicle groups compared to control and sham groups respectively (p Conclusion: ZM essential oil improves spatial learning and memory of rats with AD as assessed by MWM test. These effects are associated with decreased concentrations of hippocampal tau protein and TNFα.

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Main Subjects


Adlard PA, Tran BA, Finkelstein DI, Desmond PM, Johnston LA, Bush AI, Egan GF. 2014. A review of beta-amyloid neuroimaging in Alzheimer's disease. Front Neurosci, 8:1-23.
Ali MS, Saleem M, Ali Z, Ahmad VU. 2000. Chemistry of Zataria multiflora (Lamiaceae). Phytochemistry, 55:933-936.
Arendt T, Stieler JT, Holzer M. 2016. Tau and tauopathies. Brain Res Bull, 126:238-292.
Azizi Z, Ebrahimi S, Saadatfar E, Kamalinejad M, Majlessi N. 2012. Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia. Behav Pharmacol, 23:241-249.
Bakhtiari M, Panahi Y, Ameli J, Darvishi B. 2017. Protective effects of flavonoids against Alzheimer's disease-related neural dysfunctions. Biomed Pharmacother, 93:218-229.
Burg VK, Grimm HS, Rothhaar TL, Grosgen S, Hundsdorfer B, Haupenthal VJ, Zimmer VC, Mett J, Weingartner O, Laufs U, Broersen LM, Tanila H, Vanmierlo T, Lutjohann D, Hartmann T, Grimm MO. 2013. Plant sterols the better cholesterol in Alzheimer's disease? A mechanistical study. J Neurosci, 33:16072-16087.
Davinelli S, Sapere N, Zella D, Bracale R, Intrieri M, Scapagnini G. 2012. Pleiotropic protective effects of phytochemicals in Alzheimer's disease. Oxid Med Cell Longev, 2012:386527.
Eskandari-Roozbahani N, Shomali T, Taherianfard M. 2019. Neuroprotective effect of Zataria Multiflora essential oil on rats with Alzheimer disease: A mechanistic study. BCN,  10:85-97
Gazova I, Vlcek K, Laczo J, Nedelska Z, Hyncicova E, Mokrisova I, Sheardova K, Hort J. 2012. Spatial navigation-a unique window into physiological and pathological aging. Front Aging Neurosci, 4:1-6.
Goodman J, McIntyre CK. 2017. Impaired Spatial memory and enhanced habit memory in a rat model of post-traumatic stress disorder. Front Pharmacol, 8:1-5.
Gunaseelan S, Balupillai A, Govindasamy K, Ramasamy K, Muthusamy G, Shanmugam M, Thangaiyan R, Robert BM, Prasad Nagarajan R, Ponniresan VK, Rathinaraj P. 2017. Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells. PLoS One, 12:e0176699.
Haribabu J, Dnyanesh RS, Nattamai SPB, Prasad PK, Ramasamy K. 2017. Ru (II)‐p‐cymene thiosemicarbazone complexes as inhibitors of amyloid β (aβ) peptide aggregation and aβ‐induced cytotoxicity. Chem Select, 2: 11638-11644.
Illouz T, Madar R, Louzoun Y, Griffioen KJ, Okun E. 2016. Unraveling cognitive traits using the Morris water maze unbiased strategy classification (MUST-C) algorithm. Brain Behav Immun, 52:132-144.
Jukic M, Politeo O, Maksimovic M, Milos M, Milos M. 2007. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res, 21:259-261.
Keck S, Nitsch R, Grune T, Ullrich O. 2003. Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer's disease. J Neurochem, 85:115-122.
Majlessi N, Choopani S, Kamalinejad M, Azizi Z. 2012. Amelioration of amyloid beta-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer's disease. CNS Neurosci Ther, 18:295-301.
May BH, Lit M, Xue CC, Yang AW, Zhang AL, Owens MD, Head R, Cobiac L, Li CG, Hugel H, Story DF. 2009. Herbal medicine for dementia: a systematic review. Phytother Res, 23:447-459.
Mendez IA, Montgomery KS, LaSarge CL, Simon NW, Bizon JL, Setlow B. 2008. Long-term effects of prior cocaine exposure on Morris water maze performance. Neurobiol Learn Mem, 89:185-191.
Petrasek T, Vojtechova I, Lobellova V, Popelikova A, Janikova M, Brozka H, Houdek P, Sladek M, Sumova A, Kristofikova Z, Vales K, Stuchlik A. 2018. The McGill transgenic rat model of Alzheimer's disease displays cognitive and motor impairments, changes in anxiety and social behavior, and altered circadian activity. Front Aging Neurosci, 10:1-6.
Ren QG, Liao XM, Chen XQ, Liu GP, Wang JZ. 2007. Effects of tau phosphorylation on proteasome activity. FEBS Lett, 581:1521-1528.
Rodney T, Osier N, Gill J. 2018. Pro- and anti-inflammatory biomarkers and traumatic brain injury outcomes: A review. Cytokine, 110:248-256.
Rubio-Perez JM, Morillas-Ruiz JM. 2012. A review: inflammatory process in Alzheimer's disease, role of cytokines. Sci World J, 2012:1-15.
Sajed H, Sahebkar A, Iranshahi M. 2013. Zataria multiflora Boiss. (Shirazi thyme)--an ancient condiment with modern pharmaceutical uses. J Ethnopharmacol, 145:686-698.
Treit D, Fundytus M. 1988. Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol Biochem Behav, 31:959-962.
von Bernhardi R, Tichauer JE, Eugenín J. Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. J Neurochem 2010;112:1099-1114.
Vorhees CV, Williams MT. 2006. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc, 1:848-858.
Wilcock DM, Gordon MN, Morgan D. 2006. Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain. Nat Protoc, 1:1591-1595.
Wirths O, Multhaup G, Bayer TA. 2004. A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade. J Neurochem, 91:513-520.
Xu P, Wang K, Lu C, Dong L, Gao L, Yan M, Aibai S, Yang Y, Liu X. 2017. Protective effects of linalool against amyloid beta-induced cognitive deficits and damages in mice. Life Sci, 174:21-27.
Ying Z, Wang H, Wang G. 2012. The ubiquitin proteasome system as a potential target for the treatment of neurodegenerative diseases. Curr Pharm Des, 19:3305-3314.