Casanovas A, Olmos G, Ribera J, Boronat M A, Esquerda J E, García-Sevilla J A
Departament de Ciències Mèdiques Bàsiques, Unitat de Neurobiologia Cel.lular, Universitat de Lleida, Rovira Roure 44, E-25198 Lleida, Spain.
Br J Pharmacol. 2000 Aug;130(8):1767-76. doi: 10.1038/sj.bjp.0703485.
I(2)-imidazoline receptors are mainly expressed on glial cells in the rat brain. This study was designed to test the effect of treatment with the I(2)-imidazoline selective receptor ligand LSL 60101 [2-(2-benzofuranyl)imidazole] on the morphology of astrocytes in the neonate and adult rat brain, and to explore the putative neuroprotective effects of this glial response. Short-term (3 days) or chronic (7-10 days) treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h) enhanced the area covered by astroglial cells in sections of facial motor nucleus from neonate rats processed for glial fibrillary acidic protein (GFAP) immunostaining. Facial motoneurons surrounded by positive glial cell processes were frequently observed in sections of LSL 60101-treated rats. A similar glial response was observed in the parietal cortex of adult rats after chronic (10 days) treatment with LSL 60101 (10 mg kg(-1), i.p. every 12 h). Western-blot detection of the specific astroglial glutamate transporter GLT-1, indicated increased immunoreactivity after LSL 60101 treatment in the pons of neonate and in the parietoccipital cortex of adult rats. In the facial motor nucleus of neonate rats, the glial response after LSL 60101 treatment was associated to a redistribution of the immunofluorescence of the basic fibroblast growth factor (FGF-2) from the perinuclear area of motoneurons to cover most of their cytoplasm, suggesting a translocation of this mitogenic and neurotrophic factor towards secretion pathways. The neuroprotective potential of the above effects of LSL 60101 treatment was tested after neonatal axotomy of facial motor nucleus. Treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h from day 0 to day 10 after birth) significantly reduced (38%) motoneuron death rate 7 days after facial nerve axotomy performed on day 3 after birth. It is concluded that treatment with the I(2)-imidazoline selective receptor ligand LSL 60101 provokes morphological/biochemical changes in astroglia that are neuroprotective after neonatal axotomy.
I(2)-咪唑啉受体主要表达于大鼠脑内的神经胶质细胞上。本研究旨在测试用I(2)-咪唑啉选择性受体配体LSL 60101 [2-(2-苯并呋喃基)咪唑] 处理对新生和成年大鼠脑内星形胶质细胞形态的影响，并探索这种神经胶质细胞反应可能的神经保护作用。用LSL 60101（1 mg kg(-1)，腹腔注射，每12小时一次）进行短期（3天）或长期（7 - 10天）处理，可增加新生大鼠面神经运动核切片中经胶质纤维酸性蛋白（GFAP）免疫染色的星形胶质细胞覆盖面积。在LSL 60101处理的大鼠切片中，经常观察到被阳性胶质细胞突起包围的面神经运动神经元。在用LSL 60101（10 mg kg(-1)，腹腔注射，每12小时一次）对成年大鼠进行长期（10天）处理后，在顶叶皮质也观察到了类似的神经胶质细胞反应。对特异性星形胶质细胞谷氨酸转运体GLT-1进行蛋白质免疫印迹检测表明，LSL 60101处理后，新生大鼠脑桥和成年大鼠顶枕叶皮质中的免疫反应性增强。在新生大鼠面神经运动核中，LSL 60101处理后的神经胶质细胞反应与碱性成纤维细胞生长因子（FGF-2）免疫荧光从运动神经元的核周区域重新分布到覆盖其大部分细胞质有关，这表明这种有丝分裂和神经营养因子向分泌途径发生了易位。在新生大鼠面神经运动核轴突切断术后，测试了LSL 60101上述作用的神经保护潜力。在出生后第3天进行面神经轴突切断术后，用LSL 60101（1 mg kg(-1)，从出生后第0天至第10天腹腔注射，每12小时一次）处理可使7天后运动神经元死亡率显著降低（38%）。得出结论，用I(2)-咪唑啉选择性受体配体LSL 60101处理可引起星形胶质细胞的形态学/生化变化，这些变化在新生大鼠轴突切断术后具有神经保护作用。
