Iranian Journal of Parasitology 2016. 11(2):177-185.

Acetylcholinesterase Inhibitor Improves Learning and Memory Impairment Induced by Toxoplasma gondii Infection
Hossein MAHMOUDVAND, Vahid SHEIBANI, Hossein KESHAVARZ, Saeedeh SHOJAEE, Khadijeh ESMAEELPOUR, Naser ZIAALI

Abstract


Background: Here, we established the mouse models of chronic toxoplasmosis by T. gondii Tehran strain to provide a good understanding about defining the possible association between T. gondii exposure and learning and memory impairments. Moreover, as secondary objective of the present study, we hypothesized whether administration of an acetylcholinesterase (AChE) inhibitor could reduce learning and memory impairments induced by T. gondii infection.

Methods: Twenty-four male BALB/c mice were used to establishment of latent toxoplasmosis. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii. Donepezil (2 mg/kg) an AChE inhibitor to treat Alzheimer disease was injected intraperitoneally once a day for two weeks starting from post-infection day 90. Morris water maze (MWM) task was used to assay spatial learning and short term spatial memory in all groups. One-way ANOVA with Tukey’s post-hoc test was used to assess differences between experimental groups.  P<0.05 was considered statistically significant.

Results: Toxoplasma infection impaired spatial leaning and short term spatial memory of the infected BALB/c mice, whereas donepezil, an AChE inhibitor, improved impairments induced by Toxoplasma infection.

Conclusion: T. gondii infection through increasing AChE reduces the level of Acetylcholine (Ach) and consequently affects learning and memory activity in infected hosts, whereas, donepezil as an AChE inhibitor improves these impairments by restoring ACh levels at synapses of neurons in brain.

Keywords


Donepezil; Maze learning; Memory; Spatial learning; Toxoplasma gondii; Toxoplasmosis

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References


Hill D, Dubey J. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect. 2002; 8(10): 634-640.

Fallahi S, Seyyed Tabaei SJ, Pournia Y, Zebardast N, Kazemi B. Comparison of loop-mediated isothermal amplification (LAMP) and nested-PCR assay targeting the RE and B1 gene for detection of Toxoplasma gondii in blood samples of children with leukaemia. Diagn Microbiol Infect Dis. 2014; 79(3): 347-354.

Tavakoli Kareshk A, Keyhani A, Asadi A, Zia-Ali N, Mahmoudvand H, Mohammadi AR. Seroprevalence of Toxoplasma gondii infection among childbearing age women in the city Kerman, southeastern Iran. J Parasit Dis. DOI 10.1007/s12639-015-0724-7

Rostami A, Keshavarz H, Shojaee S, Mohebali M, Meamar AR. Frequency of Toxoplasma gondii in HIV positive patients from West of Iran by ELISA and PCR. Iran J Parasitol. 2014; 9(4): 474-81.

Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. The neurotropic parasite Toxoplasma gondii increase dopamine metabolism. PLoS One 2011; 6: e23866.

Gatkowska J, Wieczorek M, Dziadek B, Dzitko K, Dlugonska H. Sex-dependent neurotransm-itter level changes in brains of Toxoplasma gondii infected mice. Exp Parasitol. 2013; 133: 1–7.

Celik T, Kamişli O, Babür C, Cevik MO, Oztuna D, Altinayar S. Is there a relationship between Toxoplasma gondii infection and idiopathic Parkinson's disease? Scand J Infect Dis. 2010; 42(8): 604-8.

Dalimi A, Abdoli A. Latent toxoplasmosis and human. Iran J Parasitool. 2012; 2(1): 1-17.

Fekadu A, Shibre T, Cleare AJ. Toxoplasmosis as a cause for behavior disorders–overview of evidence and mechanisms. Folia Parasitol (Praha). 2010; 57(2): 105–113.

Miman O, Mutlu EA, Ozcan O, Atambay M, Karlidag R, Unal S. Is there any role of Toxoplasma gondii in the etiology of obsessive–compulsive disorder? Psychiatry Res. 2010; 177(1-2): 263–265.

Torrey EF, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull 2012; 38: 642–647.

Alipour A, Shojaee S, Mohebali M, Teh-ranidoost M, Abdi Masoleh F, Keshavarz H. Toxoplasma infection in schizophrenia patients: a comparative study withcontrol group. Iran J Parasitol. 2011;6(2):31-7.

Blockland A. Acetylcholine: a neurotransmitter for learning and memory? Brain Res Brain Res Rev. 1995; 21(3): 285–300.

Tonin AA, Da Silva AS, Thomé GR, Sangoi MB, Oliveira LS, Flores MM, et al. Influence of toxoplasmosis on acetylcholinesterase activity, nitric oxide levels and cellularlesion on the brain of mice. Pathol Res Pract. 2014;210(8): 526-32.

Tonin AA, da Silva AS, Thorstenberg ML, Castilhos LG, França RT, Leal DB, et al. Influence of Toxoplasma gondii acute infection on cholinesterase activities of Wistar rats. Korean J Parasitol. 2013; 51(4): 421-6.

Yu TS, Kim A, Kernie SG. Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis. PLoS One. 2015 25;10(2):e0118793.

Saraei M, Ghaderi Y, Mosavi T, Shahnazi M, Keshavarz H, Shojaee S. Brain cystogenesis capacity of Toxoplasma gondii, avirulent Tehran strain in mice. Asian Pacific J Trop Dis. 2014; 4(2): 739-742.

Zhu Ch, Cui L, Zhang L. Comparison of a commercial ELISA with the modified agglutination test for detection ofToxoplasma gondii antibodies in sera of naturally infected dogs and cats. Iran J Parasitol. 2012; 7(3):89-95.

Aghaei I, Shabani I, Doustar N, Nazeri M, Dehpour A. Peroxisome proliferator-activated receptor-γ activation attenuates motor and cognition impairments induced by bile duct ligation in a rat model of hepatic cirrhosis. Pharmacol Biochem Behav. 2014; 120: 133–139.

Mahmoudvand H, Ziaali N, Aghaei I, Sheibani V, Shojaee S, Keshavarz H, Shabani M. The possible association between Toxoplasma gondii infection and risk of anxiety and cognitive disorders in BALB/c mice. Pathogen Glob Health. 2015, 109(8), 369-76.

Mahmoudvand H, Saedi Dezaki E, Soleimani S, Baneshi MR, Kheirandish F, Ezatpour B, Zia-ali N. Seroprevalence and risk factors of Toxoplasma gondii infection among healthy blood donors in southeast of Iran. Parasite Immunol. 2015; 37(7): 362-367.

Mahmoudvand H, Ziaali N, Ghazvini H, Shojaee S, Keshavarz H, Esmaeeilpour K, Sheibani V. Toxoplasma gondii infection promotes neuroinflamation through cytokine networks and induced hyperalgesia in BALB/c mice. Inflammation. 2016, 39(1), 405-412.

Zhou YH, Wang XB, Jiang SF, Xu YL, Tao JP, Zhang XP, et al. Impairment of learning and memory ability in mice with latent infection of Toxoplasma gondii. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2011; 29(5):333-338.

Daniels BP, Sestito SR, Rouse ST. An expanded task battery in the Morris water maze reveals effects of Toxoplasmagondii infection on learning and memory in rats. Parasitol Int. 2015; 64(1), 5-12.

Jung BK, Pyo KH, Shin KY, Hwang YS, Lim H, Lee SJ, et al. Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memoryimpairments in a murine model of Alzheimer's disease. PLoS One. 2012; 7(3):e33312.

Haroon F, Handel U, Angenstein F, Goldschmidt J, Kreutzmann P, Lison H, et al. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice. PLoS One. 2012; 7: e35516.

Worth AR, Lymbery AJ, Thompson RC. Adaptive host manipulation by Toxoplasm gondii: fact or fiction? Trends Parasitol. 2013; 29: 150-155.

Novotná M, Hanusova J, Klose J, Preiss M, Havlicek J, Roubalová K, et al. Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host. BMC Infect Dis. 2005; 5: 54.

Webster JP. The effect of Toxoplasma gondii on animal behavior: playing cat and mouse. Schizophr Bull. 2007; 33: 752–756.

Giacobini E. New trends in cholinergic therapy for Alzheimer’s disease: nicotin agonists or cholinesterases inhibitors? Prog Brain Res. 1996; 109:311-323.

Easton A, Sankaranarayanan S, Tanghe A, Terwel D, Lin AX, Hoque N, Bourin C, Gu H, Ahlijanian M, Bristow L. Effects of sub-chronic donepezil on brain Abeta and cognition in a mouse model of Alzheimer's disease. Psychopharmacology (Berl). 2013; 230(2): 279-289.

Min D, Mao X, Wu K, Cao Y, Guo F, Zhu S, et al. Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils. Neurosci Lett. 2012; 510(1): 29-33.


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