outline

01 02 03
introduction goals result

04 05 06
CONCLUSION
discussion Hypothesis
S
Introduction - Toxoplasma gondii
 Obligate intracellular parasitic protozoan

 Causes toxoplasmosis

 Capable of infecting virtually all warm-blooded animals

 Only felids, such as domestic cats, are the only known definitive hosts

 Behavioral manipulation hypothesis

 Host-manipulation parasite (e.g Lancet liver fluke)

 Tachyzoite

Esch, Kevin J, and Christine A Petersen. “Transmission and epidemiology of zoonotic protozoal diseases of companion animals.
” Clinical microbiology reviews vol. 26,1 (2013): 58-85. doi:10.1128/CMR.00067-12
introduction
• Chronic toxoplasma infection reduces aversion of rodents to cat odors, even

attraction to

• behavioral boldness, elevated activity, reduced neophobia, and higher rates

of capture in human traps

• In wild sea otters, infections are also associated with both neuropathy and

shark predation

• With a worldwide prevalence of about 30% in the human population, latent

toxoplasmosis is a risk factor for several mental illnesses

 goals
1. identify demographic, social, and ecological determinants of T.
gondii infection in the spotted hyena (Crocuta crocuta)

2. test whether T. gondii-infected hyenas exhibit greater behavioral

boldness in the presence of lions

3. test whether T. gondii-infected hyenas have higher rates of lion-

inflicted mortality
result
result

Jupiter is the biggest

planet of them all
result
 result

1. Infected hyenas were nearly twice as likely to die by lions than by other known causes.

2. Hyenas infected as cubs, 100% of the deaths were caused by lions, while only 17% of the deaths

of hyenas not infected as cubs were caused by lions.

discussion

• infection was associated with behavioral boldness

• age-dependent relationship between T. gondii infection and host behavior

• higher rates of lion-inflicted mortality in cubs

Discussion-hypothesis
1. T. gondii traits that facilitate transmission from a wide range of intermediate

hosts into definitive hosts have evolved through natural selection on T. gondii.

2. The behavioral phenotypes of infected hyenas may simply represent “collateral

manipulation”

3. Symptoms of T. gondii infection, such as encephalitis, coincidentally alter

infected hyenas’ behaviors but did not evolve through natural selection on T.

gondii transmission.
Toxoplasma gondii

 sexually transmitted through the male ejaculate in rats

 male rats infected with toxoplasma become more attractive to females

 innate aversion to predator odor, boldness, elevated activity, reduced neophobia, and

higher rates of capture in human traps

Narrative #1: Tropism to Specific Regions of the
Brain
 behavioral changes through local manipulation of neuronal signaling and/or damage

 tropism to brain, testes, and eyes, these organs are immune-privileged

 entry into these sites through brain endothelial cells or by using dendritic immune cells

as Trojan horses

 These brain structures(nucleus accumbens, ventromedial hypothalamus, or amygdala)

are involved in decision making and generation of fear

1. Toxoplasma gondii has a widespread impact on rodent behavior

2. Infection-induced loss of fear is not specific to feline predators

3. Behavioral alterations directly correlate with cyst burden and neuroinflammation

4. Cysts are predominantly localized in cortical areas of the brain

Narrative #2: Disruption of Dopamine Signaling in
the Brain
 disruption of brain dopamine signaling

 contains two genes (AAH1 and AAH2) that bear striking sequence similarity to a

mammalian enzyme called tyrosine hydroxylase

 an intersection of generalized increase in tyrosine hydroxylase in brain with specific

distribution of complementary proteins in endogenous dopaminergic circuit could create

a rather specific behavior alteration.

Narrative #3: Hormonal Upheavals and Concomitant
Epigenetic Changes
 up-regulation of t Leydig cells testosterone synthesis

 excess testosterone shifts the host towards sexual behaviors and away from defensive behaviors

 Testosterone and/or its metabolic derivatives bind to their receptor found in the medial amygdala

 This brain region contains population of neurons expressing arginine vasopressin

 Male rats infected with toxoplasma exhibit reduced DNA methylation in promoter sites

 testosterone synthesis mediates both aspects of behavioral manipulation of sexual attractiveness

and reduction in aversion to cats.

 Also reduces aversion to cat odors in female mice and rats

Lim, Audrey, et al. "Toxoplasma gondii infection enhances
testicular steroidogenesis in rats." Molecular ecology 22.1
(2013): 102-110.
Toxoplasmosis on human

 Hitching a Ride on Immune System Cells

  Has two genes for making l-DOPA

  Using dendritic cells to get around.

  Toxo appeared to be inducing GABA production inside the dendritic cells, which excited

GABA receptors on the outside of the very same dendritic cells, and sent them zooming

through the body, and to the brain

reference
1. Boillat, Madlaina, et al. "Neuroinflammation-associated aspecific manipulation of mouse predator fear by Toxoplasma
gondii." Cell reports 30.2 (2020): 320-334.
2. Esch, Kevin J, and Christine A Petersen. “Transmission and epidemiology of zoonotic protozoal diseases of companion
animals.” Clinical microbiology reviews vol. 26,1 (2013): 58-85. doi:10.1128/CMR.00067-12
3. Gering, Eben, et al. "Toxoplasma gondii infections are associated with costly boldness toward felids in a wild
host." Nature Communications 12.1 (2021): 1-8.
4. Golcu, Doruk, Rahiwa Z. Gebre, and Robert M. Sapolsky. "Toxoplasma gondii influences aversive behaviors of female
rats in an estrus cycle dependent manner." Physiology & behavior 135 (2014): 98-103.
5. Lim, Audrey, et al. "Toxoplasma gondii infection enhances testicular steroidogenesis in rats." Molecular ecology 22.1
(2013): 102-110.
6. Singh, Dhiraj Kumar, et al. "Testosterone acts within the medial amygdala of rats to reduce innate fear to predator odor
akin to the effects of Toxoplasma gondii infection." Frontiers in Psychiatry 11 (2020): 630.
7. Vyas, Ajai. "Mechanisms of host behavioral change in Toxoplasma gondii rodent association." PLoS pathogens 11.7
(2015): e1004935.
Thank you for
listening.