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Brain Behav Immun. 2019 Feb 23. pii: S0889-1591(18)30847-X. doi: 10.1016/j.bbi.2019.02.028. [Epub ahead of print]

Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia. Electronic address: tyebji.s@wehi.edu.au.
2
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, Australia. Electronic address: seizova.s@wehi.edu.au.
3
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, Australia. Electronic address: garnham.a@wehi.edu.au.
4
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville 3052, Victoria, Australia. Electronic address: anthony.hannan@florey.edu.au.
5
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne 3052, Australia. Electronic address: tonkin@wehi.edu.au.

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.

KEYWORDS:

Cognitive impairment; Neuronal activation; Sociability; Social memory; Synaptic signalling; Toxoplasma gondii

PMID:
30807837
DOI:
10.1016/j.bbi.2019.02.028

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