Objective: Although dopaminergic neurons themselves take up most of the released dopamine (DA), a part of the DA appears to be taken up by astroglia. In the present study, we examined the protective function exerted by DA-induced astroglia via activation of the pentose-phosphate pathway (PPP) to reduce ROS.

Background: Oxygen stress plays an important role in the onset and progression of Parkinson’s disease (PD). Mitochondrial overload might be a major cause of oxygen stress; also, DA is auto-oxidized to form dopamine quinone, resulting in reactive oxygen species (ROS) production.

Methods: In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats. The rates of glucose phosphorylation in astroglia were evaluated using a modified [¹⁴C]deoxyglucose method. PPP activity was measured by a modification of the method described by Hothersall et al. using [1-¹⁴C]glucose and [6-¹⁴C]glucose after acute (60 min) or chronic (15 hours) exposure to different concentrations of DA. ROS production was measured using H₂DCFDA. Involvement of the Keap1/Nrf2 system was evaluated by immunohistochemistry.

Results: Acute exposure to DA (10, 100 µM) increased astroglial glucose consumption (123.3 ± 6.0, 108% and 130.4 ± 11.5, 115%) with lactate release, indicating enhanced glycolysis. It also robustly enhanced astroglial PPP activity (2.9 ± 0.4, 166% and 120.7 ± 3.4, 6873%). In contrast, chronic exposure to DA induced caused moderate increase of the PPP activity (2.0 ± 0.1, 118% and 2.7 ± 0.1, 163%, respectively). It also induced Nrf2 translocation to the astroglial nuclei. ROS production by DA in the absence of astroglia increased gradually over 12 hours, whereas it rather decreased in the presence of astroglia (86% vs. 75%).

Conclusions: DA released from dopaminergic neurons induced both acute and chronic enhancement of the astroglial PPP activity, which may reduce neuronal oxygen stress and play an important role in preventing the onset and progression of PD.

This study was presented in the 27th International Symposium on Cerebral Blood Flow, Metabolism and Function in Vancouver on June 28th 2015 and has not been published.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/astroglia-exert-a-neuro-protective-role-in-parkinsons-disease-by-reducing-oxygen-stress-through-dopamine-induced-activation-of-the-pentose-phosphate-pathway/