Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway

Han,Junde; Gao,Lingqi; Dong,Jing; Wang,Yingtian; Zhang,Mazhong; Zheng,Jijian

doi:10.3892/mmr.2017.6823

Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway

Authors:
- Junde Han
- Lingqi Gao
- Jing Dong
- Yingtian Wang
- Mazhong Zhang
- Jijian Zheng
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Affiliations: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, P.R. China, Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China, Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Published online on: June 20, 2017 https://doi.org/10.3892/mmr.2017.6823
Pages: 1982-1990
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Apoptosis has been identified as the primary cause of fetal alcohol spectrum disorder (FASD), and the development of methods to prevent and treat FASD have been based on the mechanisms of alcohol-induced apoptosis. The present study aimed to explore the effects of dopamine on alcohol‑induced neuronal apoptosis using whole‑mount cultures of rat retinas (postnatal day 7). Retinas were initially incubated with ethanol (100, 200 or 500 mM), and in subsequent analyses retinas were co‑incubated with ethanol (200 mM) and dopamine (10 µM). In addition, several antagonists and inhibitors were used, including a D1 dopamine receptor (D1R) antagonist (SCH23390; 10 µM), a D2R antagonist (raclopride; 40 µM), an adenosine A2A receptor (AA2AR) antagonist (SCH58261; 100 nM), an adenylyl cyclase (AC) inhibitor (SQ22536; 100 µM) and a PKA inhibitor (H‑89; 1 µM). The results demonstrated that exposure increased neuroapoptosis in the retinal ganglion cell layer (GCL) in a dose‑dependent manner. Dopamine treatment significantly attenuated ethanol‑induced neuronal apoptosis. D1R, D2R and AA2AR antagonists partially inhibited the protective effects of dopamine against ethanol‑induced apoptosis; similar results were observed with AC and PKA inhibitor treatments. In summary, the present study demonstrated that dopamine treatment may be able to attenuate alcohol‑induced neuroapoptosis in the developing rat retina by activating D1R, D2R and AA2AR, and by upregulating cyclic AMP/protein kinase A signaling.

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