Objective: In an effort to investigate the role of PTSD in the aetiology of movement disorders, we assessed changes related to PTSD using the neurotrophic factors dopamine transporter (DAT), and protein kinase B (AKT)/ Glycogen Synthase Kinase-3 (GSK3) signalling pathway in the striatum and cerebellum in a rat model for PTSD.

Background: Post-traumatic stress disorder (PTSD) is a debilitating trauma-induced mental condition that accelerates cellular aging and precipitates neurodegeneration. However, the underlying biological mechanisms are still unclear. 

Method: PTSD-like symptoms were induced using time-dependent sensitization (TDS) in adult male rats. The conditional fear test, elevated plus maze and balance beam were used to assess fear, anxiety behaviour and motor coordination. CRF, TGF β-1, GDNF, DAT concentrations were also assessed and so were AKT, pAKTser473, pAKT threo 308, GSK3 and pGSK3 ser9.

Results: The results show that TDS resulted in an increase in fear and anxiety-like behaviour. Induction of PTSD-like symptoms also resulted in increased pAKTthreo308/AKT ratio but not pAKTser473/AKT and decreased DAT concentration in the striatum. In the cerebellum, there was an increase in both pAKTthreo308/AKT and pAKTser473/AKT ratio, a decrease in pGSK3ser9/GSK3 ratio, DAT, GDNF, TGF- β-1 concentration and BDNF expression.

Conclusion: These results suggest that PTSD-like symptoms induce alterations in the AKT/GSK3 signalling pathway as well as changes in neurotrophic factor concentration. These changes increase the vulnerability of the striatum and the cerebellum to further insults that might lead to the development of movement disorders. So far it is not clear how these changes may lead to movement disorders.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/changes-in-the-akt-gsk3-pathway-in-the-cerebellum-increase-susceptibility-to-movement-disorders-in-a-rat-model-of-post-traumatic-stress-disorder/