Changes in cortical N-methyl-D-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide.
Changes in cortical N-methyl-D-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide.
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DOI：
10.1177/0004867415586601
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
McCullumsmith RE
中科院分区：
文献类型：
--
作者：
Dean B;Gibbons AS;Boer S;Uezato A;Meador-Woodruff J;Scarr E;McCullumsmith RE
在人类中，根据剂量，用氯胺酮阻断 N-甲基-d-天冬氨酸受体 (NMDAR) 可能会产生拟心理或抗抑郁作用。氯胺酮等药物的总体结果取决于剂量及其在中枢神经系统中可用结合位点的数量，为了了解后一个变量的一些信息，我们测量了精神分裂症、双相情感障碍、重度抑郁症和年龄/性别匹配对照患者的额极、背外侧前额叶、前扣带皮层和顶叶皮质中的 NMDAR。我们测量了双相情感障碍、精神分裂症和对照组的 NMDAR（使用 [3H]MK-801 结合）和 NMDAR 亚基 mRNA（GRIN：使用原位杂交）以及突触后密度蛋白 95（仅前扣带皮层；不是重度抑郁症：一种 NMDAR 突触后相关蛋白）的水平。与对照组相比，精神分裂症患者背外侧前额叶皮质外层的 NMDAR 水平较低（–17%，p = 0.01）。在双相情感障碍中，前扣带皮层中的 NMDAR 结合水平（IV-VI 层；–19%，p < 0.01）和 GRIN2C mRNA（I-VI 层；–27%，p < 0.05）中的 NMDAR 结合水平较低，背外侧前额叶皮质的外层 IV 中的 NMDAR 结合水平较低（–19%，p < 0.01）。在重度抑郁症中，额极的 GRIN2D mRNA 水平较高（+22%，p < 0.05）。在自杀完成者中，GRIN2B mRNA 水平在顶叶皮质中较高（+20%，p < 0.01），但在背外侧前额皮质中较低（–35%，p = 0.02），而突触后密度蛋白 95 在前扣带皮层中较高（+26%，p < 0.05）。这些数据表明，皮质 NMDAR 表达和突触后密度蛋白 95 存在于精神疾病和自杀完成中，并且可能导致对氯胺酮的不同反应。
In humans, depending on dose, blocking the N-methyl-d-aspartate receptor (NMDAR) with ketamine can cause psychomimetic or antidepressant effects. The overall outcome for drugs such as ketamine depends on dose and the number of its available binding sites in the central nervous system, and to understand something of the latter variable we measure NMDAR in the frontal pole, dorsolateral prefrontal, anterior cingulate and parietal cortices from people with schizophrenia, bipolar disorder, major depressive disorders and age/sex matched controls. We measured levels of NMDARs (using [3H]MK-801 binding) and NMDAR sub-unit mRNAs (GRINs: using in situ hybridisation) as well as post-synaptic density protein 95 (anterior cingulate cortex only; not major depressive disorders: an NMDAR post-synaptic associated protein) in bipolar disorder, schizophrenia and controls. Compared to controls, levels of NMDAR were lower in the outer laminae of the dorsolateral prefrontal cortex (–17%, p = 0.01) in people with schizophrenia. In bipolar disorder, levels of NMDAR binding (laminae IV–VI; –19%, p < 0.01) and GRIN2C mRNA (laminae I–VI; –27%, p < 0.05) were lower in the anterior cingulate cortex and NMDAR binding was lower in the outer lamina IV of the dorsolateral prefrontal cortex (–19%, p < 0.01). In major depressive disorders, levels of GRIN2D mRNA were higher in frontal pole (+22%, p < 0.05). In suicide completers, levels of GRIN2B mRNA were higher in parietal cortex (+20%, p < 0.01) but lower (–35%, p = 0.02) in dorsolateral prefrontal cortex while post-synaptic density protein 95 was higher (+26%, p < 0.05) in anterior cingulate cortex. These data suggest that differences in cortical NMDAR expression and post-synaptic density protein 95 are present in psychiatric disorders and suicide completion and may contribute to different responses to ketamine.
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氯胺酮和快速作用的抗抑郁药：介绍新的神经生物学的窗口，用于情绪障碍疗法。
影响因子：
10.5
作者：
Abdallah CG;Sanacora G;Duman RS;Krystal JH
通讯作者：
Krystal JH
影响因子：
17.7
作者：
Dracheva, S;Marras, SAE;Haroutunian, V
通讯作者：
Haroutunian, V
影响因子：
2.9
作者：
HOLEMANS, S;DEPAERMENTIER, F;MALOTEAUX, JM
通讯作者：
MALOTEAUX, JM
DOI：
10.1016/0169-328x(94)00219-5
发表时间：
1995-02-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
KINGSBURY, AE;FOSTER, OJF;MARSDEN, CD
通讯作者：
MARSDEN, CD
DOI：
10.1097/nen.0b013e31802c3e7d
发表时间：
2007-01-01
影响因子：
3.2
作者：
Ferrer, Isidre;Santpere, Gabriel;Kretzschmar, Hans
通讯作者：
Kretzschmar, Hans