Loss of Tyro3 causes anxiety-relevant behavioural changes in female mice.

Abstract

White-matter brain abnormalities have been found across a variety of psychiatric disorders. The extent of white matter pathology is proposed to be predictive of the severity of anxiety disorders. However, it is still unknown whether disruptions of white matter integrity precede, and are sufficient to give rise to, the behavioural symptoms. Interestingly, mood disturbances feature prominently in central demyelinating diseases such as multiple sclerosis. It is unclear whether the greater frequency of neuropsychiatric symptoms is linked to underlying neuropathology. In this study, we characterised male and female Tyro3 knockout (KO) mice using a variety of behavioural paradigms. Anxiety-related behaviours were assessed with the elevated-plus maze and light-dark box. Fear memory processing was assessed using fear conditioning and extinction paradigms. Finally, we assessed immobility time in the Porsolt swim test as a measure of depression-related behavioural despair. Surprisingly, loss of Tyro3 did not lead to manifestation of major shifts in baseline behaviour. We noted significant differences in habituation to novel environments and post-conditioning freezing levels of female Tyro3 KO mice, which are consistent with the female bias in anxiety disorders and could be indicative of maladaptive stress-responses. This study has demonstrated that white matter pathology related to a loss of Tyro3 is associated with pro-anxiety behavioural responses of female mice. Future studies could probe their contribution to increased risk for neuropsychiatric disorders when combined with stressful triggering events.