Failure of NMDA receptor hypofunction to induce a pathological reduction in PV-positive GABAergic cell markers.
Failure of NMDA receptor hypofunction to induce a pathological reduction in PV-positive GABAergic cell markers.
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DOI：
10.1016/j.neulet.2010.11.043
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发表时间：
2011-01-25
影响因子：
2.5
通讯作者：
Coyle JT
中科院分区：
文献类型：
--
作者：
Benneyworth MA;Roseman AS;Basu AC;Coyle JT
抑制性γ-氨基丁酸（GABA）中间神经元枝形亚型的皮质突触前标记物（特别是小清蛋白（PV））减少是精神分裂症中高度重复的死后发现。来自遗传和药理学研究的证据表明，N-甲基-D-天冬氨酸受体（NMDAR）介导的谷氨酸能信号转导功能减退是精神分裂症病理生理学的关键组成部分。丝氨酸消旋酶（SR）产生内源性NMDAR共激动剂D-丝氨酸，并且SR基因的破坏导致NMDAR信号传导减少。使用SR无效突变（−/−）小鼠研究NMDAR功能减退与PV表达降低之间的联系，通过内侧前额叶皮质和海马中的免疫反应（IR）细胞密度以及额叶皮质和海马脑匀浆中的蛋白质水平进行评估。与预期相反，SR −/−小鼠显示PV-IR细胞密度适度升高，脑匀浆中PV表达无差异。为了控制这些令人惊讶的结果，我们研究了成年期亚慢性苯环利定或氯胺酮治疗后小鼠和大鼠中的PV表达。PV表达在两个物种中均不受药物治疗的影响，未能重现先前发表的研究结果。我们的研究结果挑战了PV表达的病理缺陷仅仅是NMDAR功能低下的结果的假设。
Reduction in cortical presynaptic markers, notably parvalbumin (PV), for the chandelier subtype of inhibitory γ-amino-butyric acid (GABA) interneurons is a highly replicated post-mortem finding in schizophrenia. Evidence from genetic and pharmacological studies implicates hypofunction of N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic signaling as a critical component of the pathophysiology of schizophrenia. Serine racemase (SR) produces the endogenous NMDAR co-agonist D-serine, and disruption of the SR gene results in reduced NMDAR signaling. SR null mutant (−/−) mice were used to study the link between NMDAR hypofunction and decreased PV expression, assessed by immunoreactive (IR) cell density in the medial prefrontal cortex and hippocampus and protein levels in brain homogenates from the frontal cortex and hippocampus. Contrary to expectations, SR −/− mice showed modest elevations in PV-IR cell density and no difference in PV expression in brain homogenate. To control for these surprising results, we investigated PV expression in mice and rats following subchronic phencyclidine or ketamine treatments in adulthood. PV expression was not affected by drug these treatment in either species, failing to reproduce previously published findings. Our findings challenge the hypothesis that pathological deficits in PV expression are simply a consequence of NMDAR hypofunction.
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影响因子：
11
作者：
Basu, A. C.;Tsai, G. E.;Coyle, J. T.
通讯作者：
Coyle, J. T.
影响因子：
4.7
作者：
HASHIMOTO, A;NISHIKAWA, T;TAKAHASHI, K
通讯作者：
TAKAHASHI, K
影响因子：
4.7
作者：
GLOWINSKI, J;IVERSEN, LL
通讯作者：
IVERSEN, LL
白介素-6介导精神分裂症的氯胺酮模型中NADPH-氧化酶的增加。
DOI：
10.1523/jneurosci.4457-08.2008
发表时间：
2008-12-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Behrens MM;Ali SS;Dugan LL
通讯作者：
Dugan LL
影响因子：
2.7
作者：
Jenkins, Trisha A.;Harte, Michael K.;Reynolds, Gavin P.
通讯作者：
Reynolds, Gavin P.