Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway

Kyoko Mashima, Shinichi Takahashi, Kazushi Minami, Yoshikane Izawa, Takato Abe, Naoki Tsukada, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice. The rates of glucose phosphorylation in astroglia were evaluated using the [14C]deoxyglucose method. PPP activity was measured using [1-14C]glucose and [6-14C]glucose after acute (60 min) or chronic (15 hr) exposure to dopamine. ROS production was measured using 2′,7′-dichlorodihydrofluorescein diacetate. The involvement of the Kelch-like ECH-associated protein 1 (Keap1) or nuclear factor-erythroid-2-related factor 2 (Nrf2) system was evaluated using Nrf2 gene knockout mice, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction analysis for heme oxygenase-1. Acute exposure to dopamine elicited increases in astroglial glucose consumption with lactate release. PPP activity in astroglia was robustly enhanced independently of Na+-dependent monoamine transporters. In contrast, chronic exposure to dopamine induced moderate increases in PPP activity via the Keap1/Nrf2 system. ROS production from dopamine increased gradually over 12 hr. Dopamine induced neuronal cell damage that was prevented by coculturing with astroglia but not with Nrf2-deficient astroglia. Dopamine-enhanced astroglial PPP activity in both acute and chronic manners may possibly reduce neuronal oxidative stress.

Original languageEnglish
JournalASN Neuro
Volume10
DOIs
Publication statusPublished - 2018 May 1

Fingerprint

Pentose Phosphate Pathway
Astrocytes
Parkinson Disease
Dopamine
Oxidative Stress
Corpus Striatum
Glucose
Reactive Oxygen Species
Gene Knockout Techniques
Heme Oxygenase-1
Dopaminergic Neurons
Deoxyglucose
Presynaptic Terminals
Inbred C57BL Mouse
Knockout Mice
Reverse Transcription
Sprague Dawley Rats
Lactic Acid
Immunohistochemistry
Phosphorylation

Keywords

  • astrocytes
  • dopamine
  • glucose
  • glutamate
  • glutathione
  • reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway. / Mashima, Kyoko; Takahashi, Shinichi; Minami, Kazushi; Izawa, Yoshikane; Abe, Takato; Tsukada, Naoki; Hishiki, Takako; Suematsu, Makoto; Kajimura, Mayumi; Suzuki, Norihiro.

In: ASN Neuro, Vol. 10, 01.05.2018.

Research output: Contribution to journalArticle

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