title: Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.
abstract: Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lingqi
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Junde
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, 200050, China. deutschinese@163.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, China. zhengjijian626@sina.com.
authors.forename: Jijian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D007649:Ketamine / Q000633:toxicity*; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D007649:Ketamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine
keywords: Apoptosis; Development; Dopamine; Early synchronized spontaneous network activity; Ketamine; Retina