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Lesions of dopamine nigral neurons not only result in depression-like behavior (in the substantia nigra pars compacta) but also lead to a cascade of functional modifications on the activity of basal ganglia circuits, with the dysregulation of the glutamate system.12,13 This pathophysiological mechanism is also shared with Parkinson's disease, with the destabilization of the brain reward mechanism being linked to an increased risk of DE relapse.14 Note, the higher frequency of cardiovascular disorders than in other patients is also associated with the decrease in the activity of GDH, the glutamate-metabolizing enzyme

Thats why were using these two agents, one of which targets bone and the other cancer, and both of which prolong survival independently, to see if those effects can be amplified by giving them together

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