How does toxoplasmosis affect mice? - briefly
Toxoplasma gondii infection eliminates the natural fear rodents have of cat odor, making them more likely to be preyed upon, and modifies neurotransmitter activity that alters locomotion and anxiety‑related behavior. It also produces mild brain inflammation without causing overt disease.
How does toxoplasmosis affect mice? - in detail
Toxoplasma gondii infection in laboratory mice produces a spectrum of physiological, immunological, and behavioral alterations that have been extensively characterized. After oral ingestion of sporulated oocysts or intraperitoneal injection of tachyzoites, the parasite disseminates via the bloodstream, invading peripheral tissues and ultimately establishing latent cysts in the central nervous system and skeletal muscle.
During the acute phase, rapid replication of tachyzoites elicits a robust innate immune response. Pro‑inflammatory cytokines such as IFN‑γ, IL‑12, and TNF‑α rise sharply, activating macrophages and microglia. This response limits parasite proliferation but also induces transient weight loss, fever, and reduced locomotor activity. In susceptible strains, uncontrolled tachyzoite growth can cause severe hepatitis, pneumonia, and mortality within two weeks post‑infection.
Transition to the chronic phase is marked by conversion of tachyzoites to bradyzoites encased in tissue cysts. Cysts concentrate in the cerebral cortex, hippocampus, amygdala, and striatum. Their presence produces several measurable effects:
- Neurochemical shifts: increased dopamine synthesis, altered glutamate receptor expression, and dysregulated GABAergic transmission.
- Behavioral changes: loss of innate aversion to feline odor, heightened exploratory activity, and reduced anxiety‑like responses in open‑field tests.
- Cognitive impact: modest deficits in spatial memory tasks, particularly in maze navigation, associated with hippocampal cyst burden.
- Reproductive consequences: decreased fertility and litter size in chronically infected females, linked to systemic inflammation and hormonal disruption.
- Immune modulation: sustained elevation of regulatory cytokines (IL‑10, TGF‑β) that dampen Th1 responses, facilitating parasite persistence.
Strain differences influence susceptibility. C57BL/6 mice display pronounced neuroinflammation and behavioral alterations, whereas BALB/c mice tend to control parasite replication more effectively, showing fewer clinical signs. Genetic knockout models (e.g., IFN‑γ‑deficient) reveal that the absence of key cytokines dramatically increases parasite load and accelerates mortality.
Long‑term studies demonstrate that cyst density correlates with the severity of behavioral phenotypes. Experimental manipulation of dopamine pathways can reverse the loss of predator‑avoidance behavior, confirming a causal link between parasite‑induced neurotransmitter changes and altered host risk assessment.
In summary, T. gondii infection imposes acute systemic illness followed by chronic neurobiological remodeling. The organism’s capacity to form durable brain cysts drives persistent alterations in neurotransmission, immune regulation, and behavior, providing a comprehensive model for studying host‑parasite interactions and neuropsychiatric disease mechanisms.