Neuronal hyperactivity induces astrocytic expression of neurocan in the adult rat hippocampus.
Neuronal hyperactivity induces astrocytic expression of neurocan in the adult rat hippocampus.
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神经元过度活跃会诱导成年大鼠海马星形胶质细胞表达神经元蛋白聚糖。
DOI：
10.1002/glia.20329
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Deller,Thomas
中科院分区：
文献类型：
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作者：
Schwarzacher,StephanW;Vuksic,Mario;Haas,CarolaA;Burbach,GuidoJ;Sloviter,RobertS;Deller,Thomas
细胞外基质分子参与细胞的增殖、迁移、形态分化和突触可塑性等功能。细胞外基质的一个候选分子是硫酸软骨素蛋白聚糖神经聚糖。为了确定成年大鼠脑中神经蛋白聚糖的表达是否受神经元活动的调节，我们研究了电刺激乌拉坦麻醉大鼠的穿孔通路后海马神经蛋白聚糖mRNA和蛋白质表达的变化。间歇性单侧20 Hz刺激24 h后，原位杂交显示所有海马子区域中双侧胶质细胞酸性蛋白（GFAP）阳性星形胶质细胞中的neurocan mRNA增加。使用激光显微切割结合定量逆转录-聚合酶链反应（RT-PCR），在齿状分子层（穿支通路的终止区）中定量这些变化。刺激24小时后，立即检测到6倍上调，刺激后3天恢复至对照水平。Neurocan免疫反应性在双侧同样上调。免疫染色强度在第4天达到最大值，并在第14天恢复到对照水平。海马中神经聚糖表达的模式取决于电刺激的强度和持续时间。在较低强度的传入刺激条件下（2.0 Hz成对脉冲刺激4-24 h，脉冲间隔40 ms），神经聚糖mRNA和免疫反应性的增加仅限于刺激的穿通通路的同侧终止区。这种层特异性神经聚糖上调不受NMDA受体拮抗剂MK-801腹膜内应用的影响。总之，我们的数据表明，突触活动调节星形胶质细胞表达的神经蛋白。© 2006 Wiley利斯公司
Extracellular matrix molecules are involved in the cellular functions of proliferation, migration, morphological differentiation, and synaptic plasticity. One candidate molecule of the extracellular matrix is the chondroitin sulfate proteoglycan neurocan. To determine whether neurocan expression is regulated by neuronal activity in the adult rat brain, we studied changes in hippocampal neurocan mRNA and protein expression following electrical stimulation of the perforant pathway in urethane‐anesthetized rats. After 24 h of intermittent, unilateral 20 Hz stimulation, in situ hybridization revealed increased neurocan mRNA in glial fibrillary acidic protein (GFAP)‐positive astrocytes bilaterally in all hippocampal subfields. These changes were quantified in the dentate molecular layer, the termination zone of the perforant pathway, using laser microdissection in combination with quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). Immediately after 24 h stimulation, a six‐fold upregulation was detected, which returned to control levels by 3 days post‐stimulation. Neurocan immunoreactivity was similarly upregulated bilaterally. Immunostaining intensity reached a maximum by 4 days and returned to control levels by 14 days. The pattern of neurocan expression in the hippocampus depended on the intensity and duration of electrical stimulation. Under conditions of less intense afferent stimulation (4–24 h of2.0 Hz paired‐pulse stimulation, interpulse interval 40 ms), increases in neurocan mRNA and immunoreactivity were restricted to the ipsilateral termination zone of the stimulated perforant pathway. This layer‐specific neurocan upregulation was not affected by intraperitoneal application of the NMDA‐receptor antagonist MK‐801. In conclusion, our data indicate that synaptic activity regulates the astrocytic expression of neurocan in a graded manner. © 2006 Wiley‐Liss, Inc.