Impaired social behaviour and molecular mediators of associated neural circuits during chronicToxoplasma gondiiinfection in female mice

Abstract

Toxoplasma gondii (T. gondii) is a neurotropic parasite that is associated with various neuropsychiatric disorders. Rodents infected with T. gondii display a plethora of behavioural alterations, and Toxoplasma infection in humans has been strongly associated with disorders such as schizophrenia, in which impaired social behaviour is an important feature. Elucidating changes at the cellular level relevant to neuropsychiatric conditions can lead to effective therapies. Here, we compare changes in behaviour during an acute and chronic T. gondii infection in female mice. Further, we notice that during chronic phase of infection, mice display impaired sociability when exposed to a novel conspecific. Also, we show that T. gondii infected mice display impaired short-term social recognition memory. However, object recognition memory remains intact. Using c-Fos as a marker of neuronal activity, we show that infection leads to an impairment in neuronal activation in the medial prefrontal cortex, hippocampus as well as the amygdala when mice are exposed to a social environment and a change in functional connectivity between these regions. We found changes in synaptic proteins that play a role in the process of neuronal activation such as synaptophysin, PSD-95 and changes in downstream substrates of cell activity such as cyclic AMP, phospho-CREB and BDNF. Our results point towards an imbalance in neuronal activity that can lead to a wider range of neuropsychiatric problems upon T. gondii infection.

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice

“…Toxoplasma gondii (Pru:tdTomato) tachyzoites were maintained by passage on human foreskin fibroblasts and resuspended in Dulbecco's phosphate buffered saline (DPBS) to a concentration of 50,000 T. gondii tachyzoites per 200 µL DPBS (Tyebji et al, 2019). Mice allocated to T. gondii groups subsequently received a single i.p., injection of 50,000 tachyzoites and were monitored across a 6-week period for sickness behaviors as previously described (Tyebji et al, 2019).…”