Double-edged effect of astrocyte in the transition of physiopathological states in Parkinson's disease

Understanding the astrocytic effect in the cortical-basal ganglia-thalamus circuit can offer new insights into the generation mechanisms and therapeutics of Parkinson's disease (PD). By considering the effects of global couplings and astrocytic-released glial transmitters, we explore the physiopathological transition dynamics using a neural mass model. Results indicate that heightened global coupling within and across cortex and basal ganglia-thalamus induced by dopamine depletion leads to the transition in discharges, progressing from alpha-band regular to irregular physiological states, and subsequently to beta-band irregular and regular pathological states characterized by high synchronization. Interestingly, the elevated and balanced astrocytic effect could eliminate the pathological discharge. Astrocytes also exhibit stronger regulatory effects when their inhibitory factors predominate, while disrupting physiological discharge when their excitatory factors are dominant. Furthermore, the imbalance in astrocytic-released ATP-to-glutamate significantly eliminates pathological discharges, especially when the astrocytic effect mediated by ATP is dominant. Conversely, inducing pathological discharge rates are higher under glutamate dominance than in scenarios with predominant astrocytic ATP effect. The comprehensive analysis of bifurcation, power spectrum, and synchronization elucidates the significant role of astrocytes in eliminating and inducing pathological discharge, highlighting critical values associated with astrocytic excitatory factors.