Elsevier

Brain, Behavior, and Immunity

Volume 65, October 2017, Pages 95-98
Brain, Behavior, and Immunity

Loss of predator aversion in female rats after Toxoplasma gondii infection is not dependent on ovarian steroids

https://doi.org/10.1016/j.bbi.2017.04.005Get rights and content

Highlights

  • Toxoplasma reduces aversion to cat odors in female rats; akin to male rats.

  • Behavioral change is not caused by gonadal steroids; unlike male rats.

  • Behavioral change is not caused by arginine vasopressin; unlike male rats.

  • Behavioral change in males and female occur through non-analogous mechanisms.

Abstract

Toxoplasma gondii infection reduces aversion to cat odors in male rats. Relevant proximate mechanisms include interaction of gonadal testosterone and brain nonapeptide arginine-vasopressin. Both of these substrates are sexually dimorphic with preferential expression in males; suggesting either absence of behavioral change in females or mediation by analogous neuroendocrine substrates. Here we demonstrate that Toxoplasma gondii infection reduces aversion to cat odor in female rats. This change is not accompanied by altered steroid hormones; cannot be rescued by gonadal removal; and, does not depend on arginine-vasopressin. Thus behavioral change in males and female occur through non-analogous mechanisms that remain hitherto unknown.

Introduction

Male rats infected with protozoan parasite Toxoplasma gondii (henceforth Toxoplasma) exhibit reduced aversion to cat odor (Berdoy et al., 2000, Vyas et al., 2007). This behavioral change is presumed to reflect a parasitic manipulation because cats are definitive host for the parasite. It remains undetermined if the infection indeed leads to increased predation by cats under naturalistic circumstances (Worth et al., 2014). Meanwhile neuroendocrine mechanisms of the host behavioral change have been extensively studied in male laboratory rats (Hari Dass and Vyas, 2014b, House et al., 2011, Lim et al., 2013, Vyas, 2013). Several hypotheses have been proposed to account for loss of aversion to predator odor in the infected males (Gaskell et al., 2009, McConkey et al., 2013, Prandovszky et al., 2011, Vyas, 2015b). The most parsimonious of the three posits that toxoplasma infection in male rats results in an increase in testicular testosterone synthesis (Lim et al., 2013, Vyas, 2015a). The testosterone then crosses the blood-brain barrier and causes hypomethylation of the arginine vasopressin gene within the posterodorsal medial amygdala (Auger et al., 2011). This subsequently leads to increased arginine vasopressin production which then drives the behavioral change (Hari Dass and Vyas, 2014a, Hari Dass and Vyas, 2014b). This narrative has a significant limitation in that the proposed mechanism includes nodes that are sexually dimorphic. Testosterone is a predominantly male reproductive hormone that is produced in relatively smaller quantities in females (Goymann and Wingfield, 2014). Similarly medial amygdala arginine vasopressin is testosterone dependent for its transcription (Bluthe et al., 1990, Dantzer and Bluthe, 1991, Dantzer et al., 1988). This suggests that either the behavioral change is absent in females; or that it is mediated by analogous mechanisms involving steroids synthesized by ovaries. The later assumption is plausible because much of testosterone in males gets locally aromatized to estrogen after entry into the brain. We investigated these possibilities.

Section snippets

Animals and infection

Female rats of Wistar Hans strain were used, procured from InVivos Singapore. Animals were 7–8 weeks at start of experiments. A type 2 Toxoplasma strain, Prugniaud, was used for the infection at dose of 5 million lab-grown tachyzoites per animals (i.p.). Corresponding control animals were injected with sterile buffered saline. Routine management of animals and parasites was similar to earlier studies (Hari Dass and Vyas, 2014b). All experimental procedures were reviewed and approved by local

Results and discussion

We randomly divided 24 adult female rats in two experimental groups. Each group received either 5 × 106 Toxoplasma tachyzoites (Prugniaud strain) suspended in 500 μl phosphate buffered saline or buffered saline alone (i.p.). Infection did not result in sickness behavior or decrease in weight gain during the experimentation. Aversion to cat odor was quantified after establishment of chronic infection (>7 weeks, confirmed by presence of anti-Toxoplasma IgG in blood). Toxoplasma-infected female rats

Acknowledgments

This work was financially supported by Ministry of Education, Singapore (grant RG136/15).

References (26)

  • J. Flegr et al.

    Fatal attraction phenomenon in humans: cat odour attractiveness increased for toxoplasma-infected men while decreased for infected women

    PLoS Negl. Trop. Dis.

    (2011)
  • E.A. Gaskell et al.

    A unique dual activity amino acid hydroxylase in Toxoplasma gondii

    PLoS One

    (2009)
  • W. Goymann et al.

    Male-to-female testosterone ratios, dimorphism, and life history—what does it really tell us?

    Behav. Ecol.

    (2014)
  • Cited by (15)

    • Associations between Toxoplasma gondii infection and steroid hormone levels in spotted hyenas

      2022, International Journal for Parasitology: Parasites and Wildlife
    • The Adaptiveness of Host Behavioural Manipulation Assessed Using Tinbergen's Four Questions

      2021, Trends in Parasitology
      Citation Excerpt :

      Infected male rats increase testosterone production, causing epigenetic modifications in the medial amygdala of the rat’s brain. These DNA hypomethylation modifications increase the expression of the hormone arginine vasopressin which is involved in the loss of predator aversion [25,78]. Epigenetic effects on host phenotype can extend beyond their lifetime and pass down to their offspring [79].

    • Behavioral Manipulation by Toxoplasma gondii: Does Brain Residence Matter?

      2021, Trends in Parasitology
      Citation Excerpt :

      Toxoplasma rebalances the antipredator defense using its counterbalance in the form of sexual investment, and it does so by using the pre-existing neuroendocrine machinery of survival–reproduction tradeoffs. Toxoplasma also infects female rodents and causes a similar loss of fear to predator odors [47]. Yet, females do not make much testosterone and do not have much AVP in the medial amygdala.

    • Why behavioral neuroscience still needs diversity?: A curious case of a persistent need

      2020, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Related to this, human case-control studies show marked gender dimorphism in the effects of Toxoplasma infection (Flegr et al., 2011). Yet, experimental infection of female rats causes loss of aversion, similar to that seen in male rodents, and such loss is independent of ovarian steroids (Abdulai-Saiku and Vyas, 2017). These observations suggest that further investigations are needed to uncover the underlying mechanistic differences in males and female rodents and get a more complete picture.

    • Can offspring sex ratios help to explain the endocrine effects of toxoplasmosis infection on human behaviour?

      2018, Early Human Development
      Citation Excerpt :

      James [26], suggested that high levels of testosterone in infected men and of estrogen in infected women could account for the differences in behaviour of infected men and women. However, Abdulai-Saiku and Vyas [1] claim that loss of predator aversion in infected female rats is not due to ovarian steroids. This may be so, but substantial quantities of observational and experimental evidence were collated, suggesting that [26]:

    View all citing articles on Scopus
    View full text