Research advances in Toxoplasma gondii induced host mental-behavioural disorders

doi:10.12140/j.issn.1000-7423.2022.05.012

Abstract

Abstract:

Toxoplasma gondii can cause zoonotic parasitic diseases in humans and animals. Chronic toxoplasmosis induced by toxoplasma cysts could cause nervous system dysfunction, behavioural changes or mental disorders in the hosts, including reducing the natural fear of predators in the rodent host. Multiple psychiatric disorders in human hosts were also significantly associated with T. gondii chronic infection. The possible mechanisms that regulate this process include cerebral cyst infection, central neurotransmitter disorders, and epigenetic regulation of“behavioural manipulation”, but the precise mechanism remains unclear. In this review, we have summarized relevant studies of the host abnormal mental behaviour induced by T. gondii, and summarized the well-established mechanism(s) for this process.

Key words: Toxoplasma gondii, Brain cyst, Neurotransmitter, Behavioral manipulation, Epigenetics

CLC Number:

R531.8

DAI Li-sha, ZHANG Li-xin, YIN Kun. Research advances in Toxoplasma gondii induced host mental-behavioural disorders[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2022, 40(5): 642-646.

References 45

[1]	Petersen E. Toxoplasmosis[J]. Semin Fetal Neonatal Med, 2007, 12(3): 214-223. doi: 10.1016/j.siny.2007.01.011
[2]	Tyebji S,, Seizova S,, Hannan AJ, et al. Toxoplasmosis: a pathway to neuropsychiatric disorders[J]. Neurosci Biobehav Rev, 2019, 96: 72-92. doi: S0149-7634(18)30370-1 pmid: 30476506
[3]	Hernandez AV,, Thota P,, Pellegrino D, et al. A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: Is trimethoprim-sulfamethoxazole a real option?[J]. HIV Med, 2017, 18(2): 115-124. doi: 10.1111/hiv.12402 pmid: 27353303
[4]	Berdoy M,, Webster JP,, MacDonald DW. Fatal attraction in rats infected with Toxoplasma gondii[J]. Proc Biol Sci, 2000, 267(1452): 1591-1594. doi: 10.1098/rspb.2000.1182
[5]	Shen SL,, Yao YY,, Liu M, et al. Abnormal mental behavior caused by toxoplasmosis and its mechanism[J]. J Pathog Biol, 2013, 8(11): 1047-1050. (in Chinese)
	( 申善良,, 姚云英,, 刘敏, 等. 弓形虫感染引起的情智行为异常及其发生机制[J]. 中国病原生物学杂志, 2013, 8(11): 1047-1050.)
[6]	Vyas A,, Kim SK,, Giacomini N, et al. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors[J]. PNAS, 2007, 104(15): 6442-6447. doi: 10.1073/pnas.0608310104
[7]	Boillat M,, Hammoudi PM,, Dogga SK, et al. Neuroinflammation-associated aspecific manipulation of mouse predator fear by Toxoplasma gondii[J]. Cell Rep. 2020, 30(2): 320-334.e6. doi: 10.1016/j.celrep.2019.12.019
[8]	Burkinshaw J,, Kirman BH,, Sorsby A. Toxoplasmosis in relation to mental deficiency[J]. Br Med J, 1953, 1(4812): 702-704.
[9]	Wang T,, Tang ZH,, Zhao ZJ. Possible mechanisms of latent Toxoplasma gondii infection and their effect on human behavior[J]. J Pathog Biol, 2012, 7(2): 155-157. (in Chinese)
	( 汪涛,, 汤自豪,, 赵志军. 隐性弓形虫感染对人行为影响及可能机制概述[J]. 中国病原生物学杂志, 2012, 7(2): 155-157.)
[10]	Ouyang J,, Chen YK. Progress in research on the correlation between Toxoplasma gondii infection and schizophrenia[J]. Chin J Parasitol Parasit Dis, 2019, 37(1): 102-106. (in Chinese)
	( 欧阳净,, 陈耀凯. 弓形虫感染与精神分裂症相关性的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(1): 102-106.)
[11]	Sutterland AL,, Fond G,, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis[J]. Acta Psychiatr Scand, 2015, 132(3): 161-179. doi: 10.1111/acps.12423
[12]	Torrey EF,, Bartko JJ,, Lun ZR, et al. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis[J]. Schizophr Bull, 2007, 33(3): 729-736. doi: 10.1093/schbul/sbl050
[13]	Torrey EF,, Bartko JJ,, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: an update[J]. Schizophr Bull, 2012, 38(3): 642-647. doi: 10.1093/schbul/sbs043
[14]	Monroe JM,, Buckley PF,, Miller BJ. Meta-analysis of anti Toxoplasma gondii IgM antibodies in acute psychosis[J]. Schizophr Bull, 2015, 41(4): 989-998. doi: 10.1093/schbul/sbu159 pmid: 25385789
[15]	Flegr J,, Horáček J. Negative effects of latent toxoplasmosis on mental health[J]. Front Psychiatry, 2020, 10: 1012.
[16]	Flegr J. How and why Toxoplasma makes us crazy[J]. Trends Parasitol, 2013, 29(4): 156-163. doi: 10.1016/j.pt.2013.01.007
[17]	Dalimi A,, Abdoli A. Latent Toxoplasmosis and human[J]. Iran J Parasitol, 2012, 7(1): 1-17. pmid: 23133466
[18]	Flegr J. Effects of toxoplasma on human behavior[J]. Schizophr Bull, 2007, 33(3): 757-760. doi: 10.1093/schbul/sbl074
[19]	Carruthers VB,, Suzuki Y. Effects of Toxoplasma gondii infection on the brain[J]. Schizophr Bull, 2007, 33(3): 745-751. doi: 10.1093/schbul/sbm008 pmid: 17322557
[20]	Konradt C,, Ueno N,, Christian DA, et al. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system[J]. Nat Microbiol, 2016, 1: 16001. doi: 10.1038/nmicrobiol.2016.1
[21]	Berenreiterová M,, Flegr J,, Kuběna AA, et al. The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis[J]. PLoS One, 2011, 6(12): e28925. doi: 10.1371/journal.pone.0028925
[22]	Van Strien NM,, Cappaert NLM,, Witter MP. The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network[J]. Nat Rev Neurosci, 2009, 10(4): 272-282. doi: 10.1038/nrn2614 pmid: 19300446
[23]	Martynowicz J,, Augusto L,, Wek RC, et al. Guanabenz reverses a key behavioral change caused by latent toxoplasmosis in mice by reducing neuroinflammation[J]. mBio, 2019, 10(2): e00381-e00319.
[24]	Stibbs HH. Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice[J]. Ann Trop Med Parasitol, 1985, 79(2): 153-157. doi: 10.1080/00034983.1985.11811902
[25]	Strobl JS,, Goodwin DG,, Rzigalinski BA, et al. Dopamine stimulates propagation of Toxoplasma gondii tachyzoites in human fibroblast and primary neonatal rat astrocyte cell cultures[J]. J Parasitol, 2012, 98(6): 1296-1299. doi: 10.1645/GE-2760.1
[26]	Webster JP,, Lamberton PHL,, Donnelly CA, et al. Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour[J]. Proc Biol Sci, 2006, 273(1589): 1023-1030.
[27]	Martin HL,, Alsaady I,, Howell G, et al. Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells[J]. Neuroscience, 2015, 306: 50-62. doi: 10.1016/j.neuroscience.2015.08.005 pmid: 26297895
[28]	Prandovszky E,, Gaskell E,, Martin H, et al. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism[J]. PLoS One, 2011, 6(9): e23866. doi: 10.1371/journal.pone.0023866
[29]	Gaskell EA,, Smith JE,, Pinney JW, et al. A unique dual activity amino acid hydroxylase in Toxoplasma gondii[J]. PLoS One, 2009, 4(3): e4801. doi: 10.1371/journal.pone.0004801
[30]	Afonso C,, Paixão VB,, Klaus A, et al. Toxoplasma-induced changes in host risk behaviour are independent of parasite-derived AaaH2 tyrosine hydroxylase[J]. Sci Rep, 2017, 7(1): 13822. doi: 10.1038/s41598-017-13229-y pmid: 29062106
[31]	Barbosa JL,, Béla SR,, Ricci MF, et al. Spontaneous T. gondii neuronal encystment induces structural neuritic network impairment associated with changes of tyrosine hydroxilase expression[J]. Neurosci Lett, 2020, 718: 134721. doi: 10.1016/j.neulet.2019.134721
[32]	McFarland R,, Wang ZT,, Jouroukhin Y, et al. AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse[J]. Behav Brain Res, 2018, 347: 193-200. doi: S0166-4328(18)30137-2 pmid: 29555339
[33]	Wang ZT,, Harmon S,, O’Malley KL, et al. Reassessment of the role of aromatic amino acid hydroxylases and the effect of infection by Toxoplasma gondii on host dopamine[J]. Infect Immun, 2015, 83(3): 1039-1047. doi: 10.1128/IAI.02465-14 pmid: 25547791
[34]	Carrillo GL,, Ballard VA,, Glausen T, et al. Toxoplasma infection induces microglia-neuron contact and the loss of perisomatic inhibitory synapses[J]. Glia, 2020, 68(10): 1968-1986. doi: 10.1002/glia.23816
[35]	Notarangelo FM,, Wilson EH,, Horning KJ, et al. Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia[J]. Schizophr Res, 2014, 152(1): 261-267. doi: 10.1016/j.schres.2013.11.011 pmid: 24345671
[36]	David CN,, Frias ES,, Szu JI, et al. GLT-1-dependent disruption of CNS glutamate homeostasis and neuronal function by the protozoan parasite Toxoplasma gondii[J]. PLoS Pathog, 2016, 12(6): e1005643. doi: 10.1371/journal.ppat.1005643
[37]	Tyebji S,, Hannan AJ,, Tonkin CJ. Pathogenic infection in male mice changes sperm small RNA profiles and transgenerationally alters offspring behavior[J]. Cell Rep, 2020, 31(4): 107573. doi: 10.1016/j.celrep.2020.107573
[38]	Blomström A,, Karlsson H,, Wicks S, et al. Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring: a matched case-control study[J]. Schizophr Res, 2012, 140(1/2/3): 25-30. doi: 10.1016/j.schres.2012.06.035
[39]	Villares M,, Berthelet J,, Weitzman JB. The clever strategies used by intracellular parasites to hijack host gene expression[J]. Semin Immunopathol, 2020, 42(2): 215-226. doi: 10.1007/s00281-020-00779-z pmid: 32002610
[40]	Hari DS,, Vyas A. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala[J]. Mol Ecol, 2014, 23(24): 6114-6122. doi: 10.1111/mec.12888
[41]	Dvorakova-Hortova K,, Sidlova A,, Ded L, et al. Toxoplasma gondii decreases the reproductive fitness in mice[J]. PLoS One, 2014, 9(6): e96770. doi: 10.1371/journal.pone.0096770
[42]	Syn G,, Anderson D,, Blackwell JM, et al. Epigenetic dysregulation of host gene expression in Toxoplasma infection with specific reference to dopamine and amyloid pathways[J]. Infect Genet Evol, 2018, 65: 159-162. doi: 10.1016/j.meegid.2018.07.034
[43]	Kano SI,, Hodgkinson CA,, Jones-Brando L, et al. Host-parasite interaction associated with major mental illness[J]. Mol Psychiatry, 2020, 25(1): 194-205. doi: 10.1038/s41380-018-0217-z
[44]	Bao AY,, Wang HL,, Jiang MS. Toxoplasma gondii and host behavior: delicate relationship[J]. J Pathog Biol, 2007, 2(5): 389-392. (in Chinese)
	( 包安裕,, 王惠玲,, 蒋明森. 弓形虫与宿主行为: 微妙的关系[J]. 中国病原生物学杂志, 2007, 2(5): 389-392.)
[45]	Pardini L,, Dellarupe A,, Bacigalupe D, et al. Isolation and molecular characterization of Toxoplasma gondii in a colony of captive black-capped squirrel monkeys (Saimiri boliviensis)[J]. Parasitol Int, 2015, 64(6): 587-590. doi: 10.1016/j.parint.2015.08.009 pmid: 26299363