收稿日期: 2024-11-05
修回日期: 2025-04-18
网络出版日期: 2025-06-26
基金资助
国家自然科学基金面上项目(82272366);国家自然科学基金面上项目(81971955);深圳市自然科学基金面上项目(JCYJ20220530145002006);广东省自然科学基金面上项目(2021A1515012115);广东省自然科学基金面上项目(2019A1515011667)
Impact of chronic Toxoplasma gondii infection on host neuropsychiatric and behavioral well-being
Received date: 2024-11-05
Revised date: 2025-04-18
Online published: 2025-06-26
Supported by
National Natural Science Foundation of China(82272366);National Natural Science Foundation of China(81971955);Shenzhen Municipal Natural Science Foun-dation(JCYJ20220530145002006);Natural Science Foundation of Guangdong Province(2021A1515012115);Natural Science Foundation of Guangdong Province(2019A1515011667)
施承雨 , 昌运晶 , 吕芳丽 . 慢性刚地弓形虫感染对宿主神经精神和行为的影响[J]. 中国寄生虫学与寄生虫病杂志, 2025 , 43(3) : 429 -435 . DOI: 10.12140/j.issn.1000-7423.2025.03.019
Toxoplasma gondii is a globally distributed obligate intracellular parasite that causes zoonotic toxoplasmosis. Studies have found that chronic T. gondii infection leads to damage of the host’s central nervous system (such as altered neuroimmune response and neurotransmitter imbalance) through the formation of tissue cysts in the host brain, manifested as changes in mental disorders (such as schizophrenia, bipolar affective disorder, major depression, and suicide attempts), cognitive decline, Alzheimer’s disease, and behavioral changes (such as fatal attraction phenomenon, increased risk of traffic accidents, increased probability of becoming a wolf king, increased sexual attractiveness, and changes in dietary preferences), etc. This review aims to explore the relationship and underlying mechanisms between chronic T. gondii infection and host neuropsychiatric and behavioral changes.
Key words： Toxoplasma gondii; Chronic infection; Neuropsychiatric; Behavior; Mechanisms
| [1] | Moncada PA, Montoya JG. Toxoplasmosis in the fetus and newborn: An update on prevalence, diagnosis and treatment[J]. Expert Rev Anti Infect Ther, 2012, 10(7): 815-828. |
| [2] | Kazemi Arababadi M, Abdollahi SH, Ramezani M, et al. A review of immunological and neuropsychobehavioral effects of latent toxoplasmosis on humans[J]. Parasite Immunol, 2024, 46(7): e13060. |
| [3] | Montoya JG, Liesenfeld O. Toxoplasmosis[J]. Lancet, 2004, 363(9425): 1965-1976. |
| [4] | Flegr J, Lenochová P, Hodny Z, et al. Fatal attraction phenomenon in humans: Cat odour attractiveness increased for Toxoplasma-infected men while decreased for infected women[J]. PLoS Negl Trop Dis, 2011, 5(11): e1389. |
| [5] | Flegr J, Markoš A. Masterpiece of epigenetic engineering―How Toxoplasma gondii reprogrammes host brains to change fear to sexual attraction[J]. Mol Ecol, 2014, 23(24): 5934-5936. |
| [6] | Kaushik M, Knowles SL, Webster JP. What makes a feline fatal in Toxoplasma gondii’s fatal feline attraction? Infected rats choose wild cats[J]. Integr Comp Biol, 2014, 54(2): 118-128. |
| [7] | Ingram WM, Goodrich LM, Robey EA, et al. Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance[J]. PLoS One, 2013, 8(9): e75246. |
| [8] | Meyer CJ, Cassidy KA, Stahler EE, et al. Parasitic infection increases risk-taking in a social, intermediate host carnivore[J]. Commun Biol, 2022, 5(1): 1180. |
| [9] | Dellacasa-Lindberg I, Hitziger N, Barragan A. Localized recrudescence of Toxoplasma infections in the central nervous system of immunocompromised mice assessed by in vivo bioluminescence imaging[J]. Microbes Infect, 2007, 9(11): 1291-1298. |
| [10] | 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. |
| [11] | Elsheikha HM, Büsselberg D, Zhu XQ. The known and missing links between Toxoplasma gondii and schizophrenia[J]. Metab Brain Dis, 2016, 31(4): 749-759. |
| [12] | Prandovszky E, Gaskell E, Martin H, et al. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism[J]. PLoS One, 2011, 6(9): e23866. |
| [13] | Miller MW. Dopamine as a multifunctional neurotransmitter in gastropod molluscs: An evolutionary hypothesis[J]. Biol Bull, 2020, 239(3): 189-208. |
| [14] | Webster JP, Lamberton PL, 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. |
| [15] | Kar N, Misra B. Toxoplasma seropositivity and depression: A case report[J]. BMC Psychiatry, 2004, 4: 1. |
| [16] | Savitz J. The kynurenine pathway: A finger in every pie[J]. Mol Psychiatry, 2020, 25(1): 131-147. |
| [17] | 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. |
| [18] | Walker AK, Wing EE, Banks WA, et al. Leucine competes with kynurenine for blood-to-brain transport and prevents lipopolysaccharide-induced depression-like behavior in mice[J]. Mol Psychiatry, 2019, 24(10): 1523-1532. |
| [19] | Bisetegn H, Debash H, Ebrahim H, et al. Global seroprevalence of Toxoplasma gondii infection among patients with mental and neurological disorders: A systematic review and meta-analysis[J]. Health Sci Rep, 2023, 6(6): e1319. |
| [20] | Jauhar S, Johnstone M, McKenna PJ. Schizophrenia[J]. Lancet, 2022, 399(10323): 473-486. |
| [21] | Wang HL, Wang GH, Li QY, et al. Prevalence of Toxoplasma infection in first-episode schizophrenia and comparison between Toxoplasma-seropositive and Toxoplasma-seronegative schizophrenia[J]. Acta Psychiatr Scand, 2006, 114(1): 40-48. |
| [22] | Esshili A, Thabet S, Jemli A, et al. Toxoplasma gondii infection in schizophrenia and associated clinical features[J]. Psychiatry Res, 2016, 245: 327-332. |
| [23] | Guimarães AL, Richer Araujo Coelho D, Scoriels L, et al. Effects of Toxoplasma gondii infection on cognition, symptoms, and response to digital cognitive training in schizophrenia[J]. Schizophrenia, 2022, 8: 104. |
| [24] | Fuller Torrey E, 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. |
| [25] | Niebuhr DW, Millikan AM, Cowan DN, et al. Selected infectious agents and risk of schizophrenia among U.S. military personnel[J]. Am J Psychiatry, 2008, 165(1): 99-106. |
| [26] | Brown AS, Schaefer CA, Quesenberry CP Jr, et al. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring[J]. Am J Psychiatry, 2005, 162(4): 767-773. |
| [27] | Mortensen PB, Nørgaard-Pedersen B, Waltoft BL, et al. Toxoplasma gondii as a risk factor for early-onset schizophrenia: Analysis of filter paper blood samples obtained at birth[J]. Biol Psychiatry, 2007, 61(5): 688-693. |
| [28] | McGrath JJ, Lim CCW, Saha S. Cat ownership and schizophrenia-related disorders and psychotic-like experiences: A systematic review and meta-analysis[J]. Schizophr Bull, 2024, 50(3): 489-495. |
| [29] | Postolache TT, Wadhawan A, Rujescu D, et al. Toxoplasma gondii, suicidal behavior, and intermediate phenotypes for suicidal behavior[J]. Front Psychiatry, 2021, 12: 665682. |
| [30] | Zhang YF, Träskman-Bendz L, Janelidze S, et al. Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence[J]. J Clin Psychiatry, 2012, 73(8): 1069-1076. |
| [31] | Okusaga O, Langenberg P, Sleemi A, et al. Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia[J]. Schizophr Res, 2011, 133(1/2/3): 150-155. |
| [32] | Demirel ÖF, Akgül Ö, Bulu E, et al. Are bipolar disorder, major depression, and suicidality linked with Toxoplasma gondii? A seromolecular case-control study[J]. Postgrad Med, 2023, 135(2): 179-186. |
| [33] | Yang LL, Wang BY, Wu SZ, et al. Population-based cohort study of Toxoplasma gondii P22 antibody positivity correlation with anxiety[J]. J Affect Disord, 2024, 359: 41-48. |
| [34] | Akaltun İ, Kara SS, Kara T. The relationship between Toxoplasma gondii IgG antibodies and generalized anxiety disorder and obsessive-compulsive disorder in children and adolescents: A new approach[J]. Nord J Psychiatry, 2018, 72(1): 57-62. |
| [35] | Alvarado-Esquivel C, Sanchez-Anguiano LF, Hernandez-Tinoco J, et al. Toxoplasma gondii infection and mixed anxiety and depressive disorder: A case-control seroprevalence study in Durango, Mexico[J]. J Clin Med Res, 2016, 8(7): 519-523. |
| [36] | Nayeri Chegeni T, Sarvi S, Amouei A, et al. Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis[J]. PLoS Negl Trop Dis, 2019, 13(4): e0007306. |
| [37] | Gajewski PD, Falkenstein M, Hengstler JG, et al. Toxoplasma gondii impairs memory in infected seniors[J]. Brain Behav Immun, 2014, 36: 193-199. |
| [38] | Rensch P, Postolache TT, Dalkner N, et al. Toxoplasma gondii IgG serointensity and cognitive function in bipolar disorder[J]. Int J Bipolar Disord, 2024, 12(1): 31. |
| [39] | Havlícek J, Gasová ZG, Smith AP, et al. Decrease of psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis[J]. Parasitology, 2001, 122(Pt 5): 515-520. |
| [40] | Rostagno AA. Pathogenesis of Alzheimer’s disease[J]. Int J Mol Sci, 2022, 24(1): 107. |
| [41] | Nayeri Chegeni T, Sarvi S, Moosazadeh M, et al. Is Toxoplasma gondii a potential risk factor for Alzheimer’s disease? A systematic review and meta-analysis[J]. Microb Pathog, 2019, 137: 103751. |
| [42] | Wang J, Lin P, Li D, et al. Analysis of the correlation between Toxoplasma gondii seropositivity and Alzheimer's disease[J]. Pathogens, 2024, 13(11): 1021. |
| [43] | Nayeri T, Sarvi S, Sharif M, et al. Toxoplasma gondii: A possible etiologic agent for Alzheimer’s disease[J]. Heliyon, 2021, 7(6): e07151. |
| [44] | Galeh TM, Ghazvini H, Mohammadi M, et al. Effects of diverse Types of Toxoplasma gondii on the outcome of Alzheimer’s disease in the rat model[J]. Microb Pathog, 2023, 174: 105931. |
| [45] | Jung BK, Pyo KH, Shin KY, et al. Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer’s disease[J]. PLoS One, 2012, 7(3): e33312. |
| [46] | MÖhle L, Israel N, Paarmann K, et al. Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes[J]. Acta Neuropathol Commun, 2016, 4: 25. |
| [47] | Yereli K, Balcioğlu IC, Ozbilgin A. Is Toxoplasma gondii a potential risk for traffic accidents in Turkey?[J]. Forensic Sci Int, 2006, 163(1/2): 34-37. |
| [48] | Galván-Ramírez MD, Sánchez-Orozco LV, Rodríguez LR, et al. Seroepidemiology of Toxoplasma gondii infection in drivers involved in road traffic accidents in the metropolitan area of Guadalajara, Jalisco, Mexico[J]. Parasit Vectors, 2013, 6(1): 294. |
| [49] | Stepanova EV, Kondrashin AV, Sergiev VP, et al. Significance of chronic toxoplasmosis in epidemiology of road traffic accidents in Russian Federation[J]. PLoS One, 2017, 12(9): e0184930. |
| [50] | Flegr J, Havlícek J, Kodym P, et al. Increased risk of traffic accidents in subjects with latent toxoplasmosis: A retrospective case-control study[J]. BMC Infect Dis, 2002, 2: 11. |
| [51] | Gohardehi S, Sharif M, Sarvi S, et al. The potential risk of toxoplasmosis for traffic accidents: A systematic review and meta-analysis[J]. Exp Parasitol, 2018, 191: 19-24. |
| [52] | Wohlfert EA, Blader IJ, Wilson EH. Brains and brawn: Toxoplasma infections of the central nervous system and skeletal muscle[J]. Trends Parasitol, 2017, 33(7): 519-531. |
| [53] | Cook TB, Brenner LA, Robert Cloninger C, et al. “Latent” infection with Toxoplasma gondii: Association with trait aggression and impulsivity in healthy adults[J]. J Psychiatr Res, 2015, 60: 87-94. |
| [54] | Flegr J, Preiss M, Klose J, et al. Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii dopamine, a missing link between schizophrenia and toxoplasmosis?[J]. Biol Psychol, 2003, 63(3): 253-268. |
| [55] | Abdoli A, Ghaffarifar F, Sharifi Z, et al. Toxoplasma gondii infection and testosterone alteration: A systematic review and meta-analyses[J]. PLoS One, 2024, 19(4): e0297362. |
| [56] | Lim A, Kumar V, Hari Dass SA, et al. Toxoplasma gondii infection enhances testicular steroidogenesis in rats[J]. Mol Ecol, 2013, 22(1): 102-110. |
| [57] | Dass SAH, Vasudevan A, Dutta D, et al. Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males[J]. PLoS One, 2011, 6(11): e27229. |
| [58] | Roy AK, Neuhaus OW. Proof of the hepatic synthesis of a sex-dependent protein in the rat[J]. Biochim Biophys Acta, 1966, 127(1): 82-87. |
| [59] | Vasudevan A, Kumar V, Chiang YN, et al. α2u-globulins mediate manipulation of host attractiveness in Toxoplasma gondii-Rattus novergicus association[J]. ISME J, 2015, 9(9): 2112-2115. |
| [60] | Borráz-León JI, Rantala MJ, Krams IA, et al. Are Toxoplasma-infected subjects more attractive, symmetrical, or healthier than non-infected ones? Evidence from subjective and objective measurements[J]. PeerJ, 2022, 10: e13122. |
| [61] | Cuffey J, Lepczyk CA, Zhao SL, et al. Cross-sectional association of Toxoplasma gondii exposure with BMI and diet in US adults[J]. PLoS Negl Trop Dis, 2021, 15(10): e0009825. |
| [62] | Belluco S, Mancin M, Conficoni D, et al. Investigating the determinants of Toxoplasma gondii prevalence in meat: A systematic review and meta-regression[J]. PLoS One, 2016, 11(4): e0153856. |
| [63] | Reeves GM, Mazaheri S, Snitker S, et al. A positive association between T. gondii seropositivity and obesity[J]. Front Public Health, 2013, 1: 73. |
| [64] | Pleyer U, Gross U, Schlüter D, et al. Toxoplasmosis in Germany[J]. Dtsch Arztebl Int, 2019, 116(25): 435-444. |
/
| 〈 |
|
〉 |