Differential susceptibility of astrocytic and neuronal function to 3-chloropropanediol in the rat inferior colliculus
Differential susceptibility of astrocytic and neuronal function to 3-chloropropanediol in the rat inferior colliculus
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DOI：
10.1111/j.1471-4159.2010.07138.x
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发表时间：
2011-03-01
影响因子：
4.7
通讯作者：
Ray, David E.
中科院分区：
文献类型：
--
作者：
Brown, Angus M.;Skamarauskas, John;Ray, David E.
我们以前已经表明，全身给予S（+）3-氯丙二醇（3-CPD）会导致啮齿动物脑特定核团中星形胶质细胞的形态学损失，这种损失先于神经元和内皮紧密连接的损失。在这里，我们已经评估了不同的敏感性神经元和星形胶质细胞的功能，3-CPD，为了看看这是否平行的形态选择性。要做到这一点，我们已经开发了一种体内方法，通过植入微透析探针，每小时20分钟的弹丸挑战暴露于氨，并测量所产生的短暂增加细胞外谷氨酰胺：谷氨酸盐的比例，随着时间的推移，星形胶质细胞的功能进行监测。这些挑战氨暴露诱发一个稳定的反应，至少5小时，当探针植入大鼠下丘，但没有造成行为反应或形态学损害。尽管3-CPD在2小时内产生了快速和持续的氨反应消除，但下丘神经元对声音的场电位反应在给药前8小时显著下降至75.0 +/- 3.9%，但随后显著下降，在2天时达到20.5 +/- 3.7%。下丘的血流量也仅显示出晚期变化，在第2天大幅增加。从3 h开始观察到EM水平的星形胶质细胞损伤，随后从18 h开始星形胶质细胞损失至3天时的最低7 +/- 10%对照。氨反应的快速消除表明，除了选择性星形胶质细胞死亡，3-CPD还产生了早期损伤的星形胶质细胞功能，神经元功能丧失之前。3-CPD的这种初始功能选择性为星形胶质细胞-神经元相互作用的神经化学研究提供了潜在的研究工具。
P>We have previously shown that systemic administration of S(+)3-chloropropanediol (3-CPD) produces a morphological loss of astrocytes in specific nuclei of the rodent brain that precedes loss of both neurones and endothelial tight junctions. Here, we have evaluated the differential susceptibility of neuronal and astrocytic function to 3-CPD, in order to see if this parallels the morphological selectivity. To do this, we have developed an in vivo method for monitoring astrocyte function over time by giving hourly 20-min bolus challenge exposures to ammonia via an implanted microdialysis probe and measuring the resulting transient increases in the extracellular glutamine : glutamate ratio. These challenge ammonia exposures evoked a stable response for at least 5 h when the probe was implanted in the rat inferior colliculus, but caused no behavioural response or morphological damage. Although 3-CPD produced a rapid and sustained abolition of the ammonia response within 2 h, the field potential response of inferior collicular neurones to sound fell significantly to 75.0 +/- 3.9% pre-dose at up to 8 h but then fell markedly, reaching 20.5 +/- 3.7% at 2 days. Blood flow in the inferior colliculus also showed only late changes, increasing substantially at 2 days. Astrocyte damage at the EM level was seen from 3 h, followed by loss of astrocytes from 18 h to a minimum of 7 +/- 10% control at 3 days. The rapid abolition of the ammonia response suggests that in addition to selective astrocyte death, 3-CPD also produces an earlier impairment of astrocyte function that precedes loss of neuronal function. This initial functional selectivity of 3-CPD provides a potential investigative tool in neurochemical studies of astrocyte-neuronal interactions.