Zink M, Schmitt A, Henn F A, Gass P
Central Institute of Mental Health, Mannheim, Germany.
J Neural Transm (Vienna). 2004 Dec;111(12):1537-42. doi: 10.1007/s00702-004-0175-2. Epub 2004 Jun 30.
Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates glutamatergic neurotransmission and induces the expression of glutamate transporters EAAT1 and EAAT2 in newborn mouse astroglial cell cultures. Since nanomolar concentrations of PACAP exert this effect, signal transduction via the high affinity PACAP-type I-receptor PAC1 was assumed. To test this hypothesis and to assess the importance of PAC1-signalling in vivo, we analyzed glutamate transporter expression in mice with a PAC1 knockout. EAAT1 and EAAT2 expression was investigated in the hippocampus and the cerebral cortex of PAC1 mutant mice and wildtype littermates by semiquantitative in-situ-hybridization. PAC1-knockout mice show a subtle but significant reduction of EAAT1 expression in the dentate gyrus. In contrast, reduced expression levels of EAAT1 in the cerebral cortex did not reach statistical significance and EAAT2 expression was unchanged in CA3 and cerebral cortex of PAC1 mutant mice. Our data confirm the previously reported in-vitro-regulation of EAAT1 in the adult nervous system in vivo. EAAT2 expression, however, is unchanged in PAC1 knockout mice, most likely due to counterbalancing factors.
垂体腺苷酸环化酶激活多肽（PACAP）可调节谷氨酸能神经传递，并在新生小鼠星形胶质细胞培养物中诱导谷氨酸转运体EAAT1和EAAT2的表达。由于纳摩尔浓度的PACAP就能发挥这种作用，因此推测其通过高亲和力的I型PACAP受体PAC1进行信号转导。为了验证这一假设并评估PAC1信号在体内的重要性，我们分析了PAC1基因敲除小鼠中谷氨酸转运体的表达情况。通过半定量原位杂交技术，研究了PAC1突变小鼠和野生型同窝小鼠海马体和大脑皮质中EAAT1和EAAT2的表达。PAC1基因敲除小鼠齿状回中EAAT1的表达出现细微但显著的降低。相比之下，大脑皮质中EAAT1表达水平的降低未达到统计学意义，且PAC1突变小鼠的CA3区和大脑皮质中EAAT2的表达未发生变化。我们的数据证实了先前报道的在成年神经系统中EAAT1的体内体外调节作用。然而，PAC1基因敲除小鼠中EAAT2的表达未发生变化，这很可能是由于存在平衡因素。
