Back to the culture: first steps to understand the neuroprotective effect of Yerba Mate on primary dopaminergic cultures.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons. Neuroprotective strategies that promote survival and preserve the function of these neurons represent a key challenge. Chronic intake of Yerba Mate (YM) has been associated with a reduced risk of PD, and our lab has shown that YM prevents dopaminergic loss in primary cultures. In addition, unpublished results show that YM and its main active compound chlorogenic acid (CGA) activate AMPK and autophagy in SH-SY5Y cells. Since AMPK is a key regulator of cellular energy homeostasis with neuroprotective roles, this CGA-AMPK link points to AMPK as a candidate mediator of YM neuroprotection. To test this pathway, we returned to primary dopaminergic cultures that were treated with YM extract, alone or combined with the AMPK inhibitor dorsomorphin. Dopaminergic neurons were immunostained for tyrosine hydroxylase (TH) to determine survival (by cell counting), total neurite length and soma area. Our in-course results show that dorsomorphin treatment caused a marked loss of neurite outgrowth, which was fully prevented by co-administration of YM extract (restoring neurite outgrowth to control values), while YM alone increased neurite outgrowth above control. These preliminary results reproduce the protective effect of YM on dopaminergic neurons and reveal a robust, YM-sensitive effect of dorsomorphin on neurite development, which will be further characterized.