Diabetes-associated depression: the serotonergic system as a novel multifunctional target.
Diabetes-associated depression: the serotonergic system as a novel multifunctional target.
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DOI：
10.4103/0253-7613.150305
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发表时间：
2015-01
影响因子：
2.4
通讯作者：
Radhakrishnan M
中科院分区：
文献类型：
--
作者：
Prabhakar V;Gupta D;Kanade P;Radhakrishnan M
糖尿病相关抑郁症是一个研究不足的领域，但却带来了重大的疾病负担。现有常规药物疗效极低且结局不佳，部分原因可能是所涉及的机制不确定，而该机制清楚地解释了现有的合并症。本综述的主要目的是探讨这种并发症的复杂机制，以期开发具有更高疗效和特异性的潜在新靶点。数据来自数据库检索，包括PubMed、相关英语研究/综述文章和其他官方出版物的参考文献。纳入了1990年至2013年的文章，并遵循广泛的检索词标准进行数据挖掘，以便不会遗漏相关信息。使用的一些检索词包括：糖尿病引起的抑郁症、糖尿病和血清素、下丘脑-垂体-肾上腺（HPA）轴和糖尿病以及糖尿病中的糖皮质激素。在神经病理学上，由于长期持续的糖尿病状态，脑单胺能活性特别是血清素（5-羟色胺[5-HT]）系统的耗竭可能导致情绪和行为并发症，进一步增加生活质量年的恶化。5-HT系统通过多功能任务调节神经发生和可塑性，并通过复杂的受体机制控制情绪和行为活动。持续高血糖导致神经发生受损、突触可塑性降低、不期望的神经解剖学改变、神经化学缺陷和神经递质活性降低。神经营养因子和第二信使功能在分子和遗传水平上受到影响，表明糖尿病介导的神经回路失调的影响。HPA活性、糖原合成酶激酶3和胰岛素信号传导控制也被发现受到阻碍，与糖尿病进展后的5-HT系统相关。
Diabetes associated depression is a largely understudied field which nonetheless carries a significant disease burden. The very low therapeutic efficacy of the existing conventional drugs with poor outcome may be, in part, due to uncertainty of the mechanism involved that clearly explains the existing comorbidity. The main purpose of this review was to address the sophisticated mechanisms of this comorbidity with a view of developing potential novel targets with higher efficacy and specificity. Data were collected from database searches including PubMed, references from relevant English language research/review articles and other official publications. Articles from 1990 to 2013 were included, and a broad search term criteria were followed for data mining so that relevant information was not missed out. Some of the search terms used included; diabetes-induced depression, diabetes and serotonin, hypothalamic-pituitary-adrenal (HPA) axis and diabetes and glucocorticoids in diabetes. Neuropathologically, depletion of brain monoaminergic activity specifically the serotonin (5-hydroxytryptamine [5-HT]) system, due to chronically persisting diabetic state may lead to the mood and behavioral complications that further add on worsening the quality life years. The 5-HT system through multifunctional tasks regulates neurogenesis and plasticity and by complex receptor mechanism controls the emotional and behavioral activity. Persisting hyperglycemia leads to impaired neurogenesis, decreased synaptic plasticity, undesired neuro-anatomical alterations, neurochemical deficits, and reduced neurotransmitter activity. The neurotrophic factors and secondary messenger functions affected at molecular and genetic levels indicate the impact of diabetes-mediated dysregulation on neuronal circuits. HPA activity, glycogen synthase kinase 3, and insulin signaling controls were also found to be hampered, interlinked to 5-HT system following diabetic progression.
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影响因子：
3.2
作者：
Hesen, W;Joels, M
通讯作者：
Joels, M
影响因子：
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作者：
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影响因子：
2.9
作者：
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通讯作者：
Gispen, WH