Neuroparasitology

Neuroparasitology is an interdisciplinary field of biology at the intersection of neuroscience and parasitology. This field encompasses the study of parasites that infect, interact with, or otherwise affect the nervous system of their hosts, resulting in changes to brain structure, function, and/or behavior.[1][2] It integrates approaches from neuroscience, parasitology, immunology, and behavioral biology to study both pathological outcomes, such as neuroinflammation and neurological disease, and coevolutionary relationships between behavior-manipulating parasites and their hosts.

From an evolutionary perspective, parasite-induced behavioral manipulation can increase parasite fitness by enhancing their odds of survival, reproductive capacity, and/or success of transmission to the new hosts. These strategies are favored by natural selection when altered host behavior increases the likelihood that parasite genes are passed on, even if the modification is detrimental to the host. This "gene's-eye view" of evolution was proposed by Richard Dawkins in his book The Selfish Gene, arguing that natural selection acts primarily on genes and favors traits that enhance their own replication. He later expanded on this idea in his book The Extended Phenotype, introducing the concept that the effects of genes are not limited to an organism's physical body but can extend into the environment and, importantly in the case of behavior-manipulating parasites, to other organisms. Within this framework, parasite-induced extended phenotypes increase the parasite's evolutionary fitness.[3]

Scope

The field of neuroparasitology is inherently interdisciplinary, encompassing research approaches from the following areas of biology:

  • Coevolution: how the emergence of extended phenotypes in parasites and immune responses or social behaviors in the host shape their shared evolutionary trajectories.
  • Parasitology: how these parasites enter, persist within, and damage nervous tissue of their host, leading to neurological effects such as inflammation, tissue disruption, and impairment.
  • Behavior Manipulation: changes in host behavior associated with infection that benefit the parasite and how these differ from other sickness behaviors.[4]
  • Neurobiology: parasite- and host-derived factors (e.g., secondary metabolites, immune mediators, effector molecules) that may influence neural circuits, neurotransmission, and endocrine pathways.
  • Molecular biology: identification and characterization of the biomolecules involved in alteration of the nervous system.
  • Genetics: exploration of the host and parasite genomes.

Association with "zombies"

Within the neuroparasitology literature, particularly in the case of behavior manipulation, the hosts and/or their behavior-manipulating parasites are often referred to as "zombies" or "zombie-making" entities, borrowing from popular zombie horror films.[5]

Animal models and host manipulation

There are several animal–parasite pairings that are used as model systems to study behavior manipulation in the field of neuroparasitology, largely due to their conspicuous and reproducible extended phenotypes. For fungal entomopathogens, model hosts include flies,[6][7][8][9][3] beetles,[3][10][11] and ants infected by parasitic Entomophthorale or Ophiocordycipitaceae fungi.[12][13][3][14][15] These fungi collectively manipulate their hosts' behavior, driving them to higher locations for easier dispersal of infectious spores using the wind.[3] Another classic system is the zombie cockroach, produced by the emerald jewel wasp Ampulex compressa, which injects venom directly into the cockroach brain to suppress escape behavior while leaving motor abilities largely intact.[2][16][17][18] Among vertebrates, infection with Toxoplasma gondii is widely studied for its association with altered fear responses and risk-taking behavior.[19][20] In humans, sleeping sickness caused by Trypanosoma brucei serves as an important neuroparasitology model due to its effect on the central nervous system and associated disruptions of sleep, cognition, and behavior.[21][22][23]

Relevance to human health

Neuroparasitology contributes to the understanding of various human ailments, including headaches, seizures, focal neurological deficits, cognitive impairment, or other changes associated with central nervous system. Studying parasite-induced behavioral manipulation can provide insight into how neural function and behavior are related by identifying how specific molecules, neural circuits, and immune responses influence behavior. From an applied perspective, research on behavioral manipulation has informed the development of novel biocontrol strategies,[24][25] including the use of parasites (or parasite-derived compounds) to alter the behavior of agricultural pests or disease vectors. Because such approaches can target behavior rather than causing rapid mortality, they may reduce selection for resistance relative to some conventional chemical pesticides and furthermore protect non-targeted species. Together, these models connect basic research in neuroscience and parasitology with efforts to develop more sustainable methods for controlling pests and vectors that affect human health.[26][27][23]

See also

References

  1. ↑ Beckerson, William C. (2025-08-04). "Neuroparasitology: Fungal effectors induce feeding in zombie silkworms". Current Biology. 35 (15): R760–R762. Bibcode:2025CBio...35.R760B. doi:10.1016/j.cub.2025.06.069. hdl:1874/478017. ISSN 0960-9822. PMID 40763701.
  2. 1 2 Libersat, Frederic; Kaiser, Maayan; Emanuel, Stav (2018-05-01). "Mind Control: How Parasites Manipulate Cognitive Functions in Their Insect Hosts". Frontiers in Psychology. 9 572. doi:10.3389/fpsyg.2018.00572. ISSN 1664-1078. PMC 5938628. PMID 29765342.
  3. 1 2 3 4 5 de Bekker, Charissa; Beckerson, William C.; Elya, Carolyn (2021-10-26). Garsin, Danielle A. (ed.). "Mechanisms behind the Madness: How Do Zombie-Making Fungal Entomopathogens Affect Host Behavior To Increase Transmission?". mBio. 12 (5) e01872-21. Bibcode:2021mBio...1287221D. doi:10.1128/mBio.01872-21. ISSN 2150-7511. PMC 8546595. PMID 34607463.
  4. ↑ Beckerson, William C.; Laraba, Imane; Torres-Cruz, Terry J.; Steinkraus, Donald; Hajek, Ann (2024-07-17), "Mechanisms of host manipulation and mimicry in fungi", ESS Open Archive ePrints, 901, Bibcode:2024esoar.90197485B, doi:10.22541/au.172124619.90197485/v1, retrieved 2026-01-19
  5. ↑ Matthews, Carys (2025-11-05). "10 real-life zombies: These deadly brain-hijacking parasites can create suicidal rats, pulsating snails, dancing fish – and can even infect humans". Discover Wildlife. Retrieved 2026-01-31.
  6. ↑ Ulloa, Leslie Torres; Roy, Dylan; Minichiello, Angie; Bechthold, Fosca; De Bivort, Benjamin; Elya, Carolyn (2025-06-18). "Evidence that Entomophthora muscae controls the timing of host death via its own circadian clock". bioRxiv 10.1101/2025.06.18.660419.
  7. ↑ Elya, Carolyn; Lavrentovich, Danylo; Lee, Emily; Pasadyn, Cassandra; Duval, Jasper; Basak, Maya; Saykina, Valerie; de Bivort, Benjamin (2023-05-15). "Neural mechanisms of parasite-induced summiting behavior in 'zombie' Drosophila". eLife. 12 e85410. doi:10.7554/eLife.85410. ISSN 2050-084X. PMC 10259475. PMID 37184212.
  8. ↑ Naundrup, Andreas; Bohman, Björn; Kwadha, Charles A; Jensen, Annette B; Becher, Paul G; De Fine Licht, Henrik H (2022-10-01). "Pathogenic fungus uses volatiles to entice male flies into fatal matings with infected female cadavers". The ISME Journal. 16 (10): 2388–2397. Bibcode:2022ISMEJ..16.2388N. doi:10.1038/s41396-022-01284-x. ISSN 1751-7362. PMC 9477817. PMID 35831484.
  9. ↑ Elya, Carolyn; De Fine Licht, Henrik H. (2021-11-12). "The genus Entomophthora: bringing the insect destroyers into the twenty-first century". IMA Fungus. 12 (1): 34. doi:10.1186/s43008-021-00084-w. ISSN 2210-6359. PMC 8588673. PMID 34763728.
  10. ↑ Hajek, Ann E.; Steinkraus, Donald C.; Castrillo, Louela A. (2018-08-14). "Sleeping Beauties: Horizontal Transmission via Resting Spores of Species in the Entomophthoromycotina". Insects. 9 (3): 102. doi:10.3390/insects9030102. ISSN 2075-4450. PMC 6165266. PMID 30110948.
  11. ↑ Steinkraus, Donald C.; Hajek, Ann E.; Liebherr, Jim K. (2017-09-01). "Zombie soldier beetles: Epizootics in the goldenrod soldier beetle, Chauliognathus pensylvanicus (Coleoptera: Cantharidae) caused by Eryniopsis lampyridarum (Entomophthoromycotina: Entomophthoraceae)". Journal of Invertebrate Pathology. 148: 51–59. Bibcode:2017JInvP.148...51S. doi:10.1016/j.jip.2017.05.002. ISSN 0022-2011. PMID 28535871.
  12. ↑ Beckerson, William C.; Werner, Steffen; Goebbels, Maite; Ramalho, João J.; Swafford, Andrew J. M.; Soroka, Ilia; Wingert, Sinah T.; Boxem, Mike; Ruijtenberg, Suzan (2025-09-13). "The First of Us: Ophiocordyceps use a novel scramblase-binding peptide to manipulate zombie ants". bioRxiv 10.1101/2025.09.09.674826.
  13. ↑ Beckerson, William C.; Krider, Courtney; Mohammad, Umar A.; de Bekker, Charissa (2023-09-01). "28 minutes later: investigating the role of aflatrem-like compounds in Ophiocordyceps parasite manipulation of zombie ants". Animal Behaviour. 203: 225–240. Bibcode:2023AnBeh.203..225B. doi:10.1016/j.anbehav.2023.06.011. ISSN 0003-3472.
  14. ↑ Will, Ian; Das, Biplabendu; Trinh, Thienthanh; Brachmann, Andreas; Ohm, Robin A; de Bekker, Charissa (2020-07-01). "Genetic Underpinnings of Host Manipulation by Ophiocordyceps as Revealed by Comparative Transcriptomics". G3 Genes|Genomes|Genetics. 10 (7): 2275–2296. doi:10.1534/g3.120.401290. ISSN 2160-1836. PMC 7341126. PMID 32354705.
  15. ↑ Araújo, J. P. M.; Evans, H. C.; Fernandes, I. O.; Ishler, M. J.; Hughes, D. P. (2020-11-01). "Zombie-ant fungi cross continents: II. Myrmecophilous hymenostilboid species and a novel zombie lineage". Mycologia. 112 (6): 1138–1170. doi:10.1080/00275514.2020.1822093. ISSN 0027-5514. PMID 33146584.
  16. ↑ Libersat, F.; Gal, R. (2014-07-01). "Wasp Voodoo Rituals, Venom-Cocktails, and the Zombification of Cockroach Hosts". Integrative and Comparative Biology. 54 (2): 129–142. doi:10.1093/icb/icu006. ISSN 1540-7063. PMID 24706086.
  17. ↑ Libersat, Frederic; Gal, Ram (2013-01-01). "What can parasitoid wasps teach us about decision-making in insects?". Journal of Experimental Biology. 216 (1): 47–55. Bibcode:2013JExpB.216...47L. doi:10.1242/jeb.073999. ISSN 1477-9145. PMID 23225867.
  18. ↑ Gal, Ram; Libersat, Frederic (September 2010). "On predatory wasps and zombie cockroaches: Investigations of free will and spontaneous behavior in insects". Communicative & Integrative Biology. 3 (5): 458–461. doi:10.4161/cib.3.5.12472. ISSN 1942-0889. PMC 2974080. PMID 21057640.
  19. ↑ Abdulai-Saiku, Samira; Tong, Wen Han; Vyas, Ajai (2021-05-01). "Behavioral Manipulation by Toxoplasma gondii: Does Brain Residence Matter?". Trends in Parasitology. 37 (5): 381–390. doi:10.1016/j.pt.2020.12.006. ISSN 1471-4922. PMID 33461902.
  20. ↑ Vyas, Ajai (2015-07-23). Knoll, Laura J (ed.). "Mechanisms of Host Behavioral Change in Toxoplasma gondii Rodent Association". PLOS Pathogens. 11 (7) e1004935. doi:10.1371/journal.ppat.1004935. ISSN 1553-7374. PMC 4512725. PMID 26203656.
  21. ↑ MacLean, Lorna; Reiber, Hansotto; Kennedy, Peter G. E.; Sternberg, Jeremy M. (2012-10-25). "Stage Progression and Neurological Symptoms in Trypanosoma brucei rhodesiense Sleeping Sickness: Role of the CNS Inflammatory Response". PLOS Neglected Tropical Diseases. 6 (10) e1857. doi:10.1371/journal.pntd.0001857. ISSN 1935-2735. PMC 3493381. PMID 23145191.
  22. ↑ Rodgers, Jean (December 2010). "Trypanosomiasis and the brain". Parasitology. 137 (14): 1995–2006. doi:10.1017/S0031182009991806. ISSN 1469-8161. PMID 20028610.
  23. 1 2 Kennedy, Peter G.E. (2004-02-15). "Human African trypanosomiasis of the CNS: current issues and challenges". Journal of Clinical Investigation. 113 (4): 496–504. doi:10.1172/JCI21052. ISSN 0021-9738. PMC 338269. PMID 14966556.
  24. ↑ Tang, Dan; Chen, Jiani; Zhang, Yubo; Tang, Xingyuan; Wang, Xinmiao; Yu, Chaonan; Cheng, Xianxian; Zhang, Junwei; Shi, Wenqi; Zhen, Qing; Liu, Shuxing; Huang, Yizhou; Ning, Jiali; Zhu, Guoding; Zhang, Meichun (December 2025). "Engineered Metarhizium fungi produce longifolene to attract and kill mosquitoes". Nature Microbiology. 10 (12): 3075–3093. doi:10.1038/s41564-025-02155-9. ISSN 2058-5276. PMID 41136733.
  25. ↑ Zhang, Dinghai; Qi, Haidi; Zhang, Feng (2025-01-27). "Parasitism by Entomopathogenic Fungi and Insect Host Defense Strategies". Microorganisms. 13 (2): 283. doi:10.3390/microorganisms13020283. ISSN 2076-2607. PMC 11858285. PMID 40005650.
  26. ↑ Sutterland, Arjen L.; Kuin, Anne; Kuiper, Bouke; Gool, Tom van; Leboyer, Marion; Fond, Guillaume; Haan, Lieuwe de (July 2019). "Driving us mad: the association of Toxoplasma gondii with suicide attempts and traffic accidents – a systematic review and meta-analysis". Psychological Medicine. 49 (10): 1608–1623. doi:10.1017/S0033291719000813. ISSN 0033-2917. PMID 31010440.
  27. ↑ Gohardehi, Shaban; Sharif, Mehdi; Sarvi, Shahabeddin; Moosazadeh, Mahmood; Alizadeh-Navaei, Reza; Hosseini, Seyed Abdollah; Amouei, Afsaneh; Pagheh, Abdolsattar; Sadeghi, Mitra; Daryani, Ahmad (2018-08-01). "The potential risk of toxoplasmosis for traffic accidents: A systematic review and meta-analysis". Experimental Parasitology. 191: 19–24. doi:10.1016/j.exppara.2018.06.003. ISSN 0014-4894. PMID 29906469.
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