A Behavioral and Molecular Study; Ameliorated Anxiety-like Behavior and Cognitive Dysfunction in a Rat Model of Chronic Unpredictable Stress Treated with Oregano Extract

Overview

Journal Brain Behav

Specialty Psychology

Date 2022 Jul 28

PMID 35898162

Authors

Parvaneh Mohseni-Moghaddam

Manijeh Dogani

Motahare Hatami

Samira Roohollahi

Azam Amiresmaeli

Nayereh Askari

Affiliations

Soon will be listed here.

Abstract

Objective: Chronic stress is considered a severe risk factor leading to various disorders, including anxiety and cognitive decline. The present study aimed to investigate the effects of Origanum vulgare (oregano) extract on improving anxiety-like behavior and learning and memory defection caused by chronic unpredictable stress (CUS).

Method: A 10-day CUS protocol was executed on male rats, and on day 10, their anxiety, learning, and memory status were evaluated. After that, in addition to the CUS, the rats were treated with the oregano extract for 2 weeks. Then, the expression of BDNF, TrkB, and TLR2/4 genes in the hippocampus and prefrontal cortex of the rats was evaluated. Also, the liver- and kidney-related serum parameters, including triglycerides, total cholesterol, HDL, LDL, creatinine, urea, serum glucose, alanine aminotransferase, and aspartate aminotransferase were assessed. Further, the extract's lethal effect and its impact on animals' body weight were investigated.

Results: Behavioral tests confirmed the anxiety-like behavior and learning-memory function impairment caused by CUS. In contrast, the administration of the extract could significantly alleviate the mental deficiencies and diminished anxiety-like behaviors. Molecular assessments showed that CUS could markedly decrease the BDNF and TrkB genes' expression levels while increasing that of TLR2 and TLR4. In contrast, in extract-treated animals, mRNA levels of BDNF and TrkB considerably increased, yet TLR2 and TLR4 mRNA levels reduced. Additionally, consumption of the extract caused weight gain, while having no lethality and detrimental effect on the liver and kidneys functions.

Conclusions: These findings indicate the anxiolytic properties of the extract and its improving effect on cognitive dysfunction.

Citing Articles

Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway.

Yuan H, Xu Y, Jiang H, Jiang M, Zhang L, Wei S Mol Brain. 2025; 18(1):8.

PMID: 39905541 PMC: 11796198. DOI: 10.1186/s13041-025-01178-x.

Antidepressant- and Anxiolytic-Like Effect of the Froriepia subpinnata Extract in the Rat: Neurochemical Correlates.

Samandari-Bahraseman M, Esmaeilzadeh-Salestani K, Dogani M, Khaleghdoust B, Hatami N, Esmaeili-Mahani S Brain Behav. 2024; 14(11):e70171.

PMID: 39607287 PMC: 11603432. DOI: 10.1002/brb3.70171.

A diet enriched with fruits improves the female rats' reproductive system.

Dogani M, Askari N, Hesari A J Tradit Complement Med. 2024; 14(3):335-342.

PMID: 38707920 PMC: 11068987. DOI: 10.1016/j.jtcme.2023.09.004.

Methyl jasmonate ameliorates pain-induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation.

Mohammadinia F, Esmaeili-Mahani S, Abbasnejad M, Dogani M, Poorrahimi A Brain Behav. 2024; 14(5):e3502.

PMID: 38680072 PMC: 11056706. DOI: 10.1002/brb3.3502.

A behavioral and molecular study; ameliorated anxiety-like behavior and cognitive dysfunction in a rat model of chronic unpredictable stress treated with oregano extract.

Mohseni-Moghaddam P, Dogani M, Hatami M, Roohollahi S, Amiresmaeli A, Askari N Brain Behav. 2022; 12(8):e2727.

PMID: 35898162 PMC: 9392516. DOI: 10.1002/brb3.2727.

References

Postu P, Gorgan D, Cioanca O, Russ M, Mikkat S, Glocker M . Memory-Enhancing Effects of Essential Oil in an Alzheimer's Amyloid beta1-42 Rat Model: A Molecular and Behavioral Study. Antioxidants (Basel). 2020; 9(10). PMC: 7600529. DOI: 10.3390/antiox9100919. View

Cavalcante Melo F, Venancio E, de Sousa D, de Franca Fonteles M, de Vasconcelos S, Barros Viana G . Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission. Fundam Clin Pharmacol. 2009; 24(4):437-43. DOI: 10.1111/j.1472-8206.2009.00788.x. View

Sharifi-Rigi A, Heidarian E, Amini S . Protective and anti-inflammatory effects of hydroalcoholic leaf extract of Origanum vulgare on oxidative stress, TNF-α gene expression and liver histological changes in paraquat-induced hepatotoxicity in rats. Arch Physiol Biochem. 2018; 125(1):56-63. DOI: 10.1080/13813455.2018.1437186. View

Chen C, Shih Y, Hung Y, Hsueh Y . Beyond defense: regulation of neuronal morphogenesis and brain functions via Toll-like receptors. J Biomed Sci. 2019; 26(1):90. PMC: 6827257. DOI: 10.1186/s12929-019-0584-z. View

Nie X, Kitaoka S, Tanaka K, Segi-Nishida E, Imoto Y, Ogawa A . The Innate Immune Receptors TLR2/4 Mediate Repeated Social Defeat Stress-Induced Social Avoidance through Prefrontal Microglial Activation. Neuron. 2018; 99(3):464-479.e7. DOI: 10.1016/j.neuron.2018.06.035. View

Khorrami S, Zarepour A, Zarrabi A . Green synthesis of silver nanoparticles at low temperature in a fast pace with unique DPPH radical scavenging and selective cytotoxicity against MCF-7 and BT-20 tumor cell lines. Biotechnol Rep (Amst). 2019; 24:e00393. PMC: 6864360. DOI: 10.1016/j.btre.2019.e00393. View

Lam V, Raineki C, Ellis L, Yu W, Weinberg J . Interactive effects of prenatal alcohol exposure and chronic stress in adulthood on anxiety-like behavior and central stress-related receptor mRNA expression: Sex- and time-dependent effects. Psychoneuroendocrinology. 2018; 97:8-19. PMC: 6424330. DOI: 10.1016/j.psyneuen.2018.06.018. View

Mao S, Hua R, Zhao X, Qin X, Sun Z, Zhang Y . Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-κB pathway. J Neurotrauma. 2012; 29(10):1941-59. DOI: 10.1089/neu.2011.2244. View

Li Y, Chen Y, Gao X, Zhang Z . The behavioral deficits and cognitive impairment are correlated with decreased IGF-II and ERK in depressed mice induced by chronic unpredictable stress. Int J Neurosci. 2017; 127(12):1096-1103. DOI: 10.1080/00207454.2017.1337014. View

10.

Blossom V, Gokul M, Kumar N, Kini R, Nayak S, Bhagyalakshmi K . Chronic unpredictable stress-induced inflammation and quantitative analysis of neurons of distinct brain regions in Wistar rat model of comorbid depression. Vet World. 2020; 13(9):1870-1874. PMC: 7566234. DOI: 10.14202/vetworld.2020.1870-1874. View

11.

Cerqueira J, Mailliet F, Almeida O, Jay T, Sousa N . The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci. 2007; 27(11):2781-7. PMC: 6672565. DOI: 10.1523/JNEUROSCI.4372-06.2007. View

12.

Mousavi A, Askari N, Vaez-Mahdavi M . Augmentation of morphine-conditioned place preference by food restriction is associated with alterations in the oxytocin/oxytocin receptor in rat models. Am J Drug Alcohol Abuse. 2019; 46(3):304-315. DOI: 10.1080/00952990.2019.1648483. View

13.

Dogani M, Askari N, Kalantari-Hesari A, Hosseini Rahbar F . The effects of as a libido booster and sexual enhancer on the reproductive system of male rats. J Tradit Complement Med. 2022; 12(4):345-353. PMC: 9209825. DOI: 10.1016/j.jtcme.2021.09.007. View

14.

Liu D, Wang Z, Gao Z, Xie K, Zhang Q, Jiang H . Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behav Brain Res. 2014; 271:116-21. DOI: 10.1016/j.bbr.2014.05.068. View

15.

Meynaghizadeh-Zargar R, Sadigh-Eteghad S, Mohaddes G, Salehpour F, Rasta S . Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model. Lasers Med Sci. 2019; 35(3):573-584. DOI: 10.1007/s10103-019-02851-z. View

16.

Zhou Z, Hou J, Mo Y, Ren M, Yang G, Qu Z . Geniposidic acid ameliorates spatial learning and memory deficits and alleviates neuroinflammation via inhibiting HMGB-1 and downregulating TLR4/2 signaling pathway in APP/PS1 mice. Eur J Pharmacol. 2019; 869:172857. DOI: 10.1016/j.ejphar.2019.172857. View

17.

Kaewwongse M, Sanesuwan K, Pupa P, Bullangpoti V . Essential oil compounds as stress reducing agents in rats. Commun Agric Appl Biol Sci. 2014; 78(2):167-72. View

18.

Jia H, Li Q, Zhou C, Yu M, Yang Y, Zhang H . Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression. Sci Rep. 2016; 6:23441. PMC: 4804211. DOI: 10.1038/srep23441. View

19.

Bondi C, Rodriguez G, Gould G, Frazer A, Morilak D . Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology. 2007; 33(2):320-31. DOI: 10.1038/sj.npp.1301410. View

20.

Mohseni-Moghaddam P, Sadr S, Roghani M, Arabzadeh S, Khamse S, Zamani E . Huperzine A ameliorates cognitive dysfunction and neuroinflammation in kainic acid-induced epileptic rats by antioxidant activity and NLRP3/caspase-1 pathway inhibition. Clin Exp Pharmacol Physiol. 2019; 46(4):360-372. DOI: 10.1111/1440-1681.13064. View