The possible association between Toxoplasma gondii infection and risk of anxiety and cognitive disorders in BALB/c mice

Pathog Glob Health. 2015;109(8):369-76. doi: 10.1080/20477724.2015.1117742.

Abstract

There are conflicting reports concerning the association of Toxoplasma gondii infection with increased risk of mental disorders. This investigation will provide a good understanding about defining the possible association between T. gondii exposure and risk of anxiety and cognitive alterations. Besides, a secondary objective of this study was to determine the effect of pioglitazone administration on the possible alterations induced by T. gondii exposure. Male BALB/c mice were used for this study. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii. Pioglitazone (20 mg/kg, i.p.1/day) was administered to the animals for 2 weeks before behavioural tests. Behavioural tests including open-field, elevated plus-maze and passive avoidance learning were evaluated in the groups. Since cytokines were implicated as a contributing factor for mood disorders, the mRNA levels of TNF-α, IL-1β, IL-6 as well as inducible nitric oxide synthase (iNOs) were examined by real-time PCR. Findings demonstrated that T. gondii caused anxiety-like symptoms and impaired cognitive functions of the infected BALB/c mice, whereas pioglitazone, a peroxisome proliferator-activated receptor agonist, showed a promising effect against the cognitive impairments induced by Toxoplasma infection. The results also revealed that the mRNA levels of the aforementioned cytokines were significantly (p < 0.05) increased in the infected mice compared to the uninfected BALB/c ones. Pioglitazone can be offered as a potential neuroprotective agent in the treatment of patients with T. gondii infection that manifests anxiety and cognitive impairments; however, further studies are needed to clarify the exact mechanisms.

Keywords: Anxiety; Cognitive function; Cytokine; Learning; Pioglitazone; Toxoplasma gondii.

MeSH terms

  • Animals
  • Anxiety / etiology
  • Anxiety / genetics
  • Anxiety / metabolism
  • Anxiety / psychology*
  • Behavior, Animal
  • Cognition
  • Disease Models, Animal
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred BALB C
  • Toxoplasma / physiology*
  • Toxoplasmosis / complications*
  • Toxoplasmosis / genetics
  • Toxoplasmosis / parasitology
  • Toxoplasmosis / psychology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha