Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression
Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression
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DOI：
10.1038/npp.2011.60
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发表时间：
2011-07-01
影响因子：
7.6
通讯作者：
Kehr, Jan
中科院分区：
文献类型：
--
作者：
Hascup, Kevin N.;Hascup, Erin R.;Kehr, Jan
尽管有许多针对生物胺的药物用于重度抑郁症（抑郁症），但由于其反应率低（B30%）和起效慢（2-4周），对新疗法的研究仍在继续。为了更好地了解谷氨酸在抑郁症中的作用，我们使用了一种基于酶的微电极阵列（MEA），具有快速的时间（2 Hz）和高空间分辨率（15 × 333 μ m）的谷氨酸措施的选择性。将这些MEA长期植入3至6个月大和12至15个月大的弗林德斯敏感系（FSL）和对照弗林德斯抵抗系（FRL）大鼠的前额叶皮层，这是一种经验证的遗传性啮齿动物抑郁症模型。尽管在3至6个月的FRL和FSL大鼠之间未观察到谷氨酸动力学变化，但在植入后第3- 5天，与3至6个月的FSL和年龄匹配的FRL大鼠相比，在12至15个月的FSL大鼠中观察到静息谷氨酸水平显著增加。我们的MEA还首次记录了所有四组大鼠静息谷氨酸波动的独特现象，我们称之为谷氨酸瞬变。虽然这些事件只持续了几秒钟，但它们确实发生在整个测试范式中。与3- 6个月大的FSL和年龄匹配的FRL大鼠相比，12- 15个月大的FSL大鼠中这些谷氨酸爆发事件的平均浓度显著增加。这些研究为进一步研究抑郁症大鼠模型中的紧张性和阶段性谷氨酸信号传导奠定了基础，以更好地了解谷氨酸信号传导在抑郁症中的潜在作用。Neuropsychopharmacology（2011）36，1769-1777; doi：10.1038/npp.2011.60; 2011年4月27日在线发表
Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (B30%) and slow onset of action (2-4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 x 333 mu m) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3- 5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression. Neuropsychopharmacology (2011) 36, 1769-1777; doi: 10.1038/npp.2011.60; published online 27 April 2011