Department of Psychiatry and Neurosciences, Quebec City, Quebec, Canada; Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada.
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
Biol Psychiatry. 2014 Mar 15;75(6):479-86. doi: 10.1016/j.biopsych.2012.11.024. Epub 2013 Jan 7.
Dysfunctions in brain dopamine and serotonin neurotransmission are believed to be involved in the etiology of psychiatric disorders, and electroretinogram (ERG) anomalies have been reported in psychiatric patients. The goal of this study was to evaluate whether ERG anomalies could result from central dopamine or serotonin dysfunctions or from changes in the retinal bioavailability of these neurotransmitters.
Photopic and scotopic ERGs were recorded in R439H tryptophan hydroxylase 2 knockin (Tph2-KI) mice that have an approximately 80% decrease in brain serotonin and dopamine transporter knockout (DAT-KO) mice showing a fivefold increase in brain extracellular dopamine. Dopamine and serotonin retinal and striatal tissue content were also measured. The role of dopamine D1 receptors (D1R) and D2 receptors (D2R) in the ERG responses was evaluated in D1R-KO and D2R-KO mice.
An increase in photopic b-wave implicit time was observed in Tph2-KI mice (wildtype = 24.25 msec, KI = 25.22 msec; p = .011). The DAT-KO mice showed a decrease in rod sensitivity (wildtype =-1.97 log units, KO =-1.81 log units; p = .014). In contrast to remarkable alterations in brain levels, no changes in dopamine and serotonin retinal content were found in DAT-KO and Tph2-KI mice, respectively. The D1R-KO mice showed anomalies in photopic and scotopic maximal amplitude, whereas D2R-KO mice showed higher oscillatory potentials relative contribution to the b-wave amplitude.
Alterations in central dopamine and serotonin neurotransmission can affect the ERG responses. The ERG anomalies reported in psychiatric disorders might serve as biomarkers of central monoaminergic dysfunction, thus promoting ERG measurements as a useful tool in psychiatric research.
据信，大脑多巴胺和 5-羟色胺神经递质功能障碍与精神疾病的病因有关，并且在精神疾病患者中已经报道了视网膜电图（ERG）异常。本研究的目的是评估 ERG 异常是否可能由中枢多巴胺或 5-羟色胺功能障碍或这些神经递质的视网膜生物利用度变化引起。
在脑内 5-羟色胺和多巴胺转运体敲除（DAT-KO）小鼠（脑内多巴胺增加五倍）和色氨酸羟化酶 2 敲入（Tph2-KI）小鼠（脑内 5-羟色胺减少约 80%）中记录明适应和暗适应 ERG。还测量了多巴胺和 5-羟色胺视网膜和纹状体组织含量。在多巴胺 D1 受体（D1R）和 D2 受体（D2R）敲除（D1R-KO 和 D2R-KO）小鼠中评估了它们在 ERG 反应中的作用。
Tph2-KI 小鼠的明适应 b 波潜时增加（野生型=24.25 毫秒，KI=25.22 毫秒；p=0.011）。DAT-KO 小鼠的杆状细胞灵敏度降低（野生型=-1.97 对数单位，KO=-1.81 对数单位；p=0.014）。与大脑水平的显著改变相反，在 DAT-KO 和 Tph2-KI 小鼠中均未发现多巴胺和 5-羟色胺视网膜含量的变化。D1R-KO 小鼠的明适应和暗适应最大振幅异常，而 D2R-KO 小鼠的振荡电位对 b 波振幅的相对贡献更高。
中枢多巴胺和 5-羟色胺神经递质的改变会影响 ERG 反应。在精神疾病中报道的 ERG 异常可能作为中枢单胺能功能障碍的生物标志物，从而促进 ERG 测量作为精神科研究中的有用工具。
