Stoltenburg-Didinger G, Pünder I, Peters B, Marcinkowski M, Herbst H, Winneke G, Wiegand H
Institute of Neuropathology, Universitätsklinikum Benjamin Franklin, Berlin, Germany.
Histochem Cell Biol. 1996 Jun;105(6):431-42. doi: 10.1007/BF01457656.
The astroglial cytoskeletal element, glial fibrillary acidic protein (GFAP), is a generally accepted sensitive indicator for neurotoxic effects in the mature brain. We used GFAP as a marker for structural changes in rat hippocampus related to chronic low level lead exposure during different developmental periods. Four groups of rats were investigated: a control group, a perinatal group, which was exposed during brain development (E0-P16), a permanent group, exposed during and after brain development (E0-P100), and a postweaning group, exposed after brain development (P16-P100). Sections were processed for light microscopy (hematoxylin-eosin, Nissl, periodic acid Schiff (PAS) and GFAP-specific immunohistology), for electron microscopy, and for in-situ hybridization (GFAP). Sections were prepared from animals tested for active avoidance learning (AAL) and long-term potentiation (LTP). Chronic lead exposure did not affect glial and neuronal functions, as assessed by LTP and AAL, when lead exposure started after brain development (postweaning group). In this group, astrocytes displayed increased GFAP and GFAP gene transcript levels. However, lead exposure affected neuronal and glial function when the intoxication fell into the developmental period of the brain (perinatal and permanent groups). In these groups, LTP and AAL were impaired, and astrocytes failed to react to the toxic exposure with an adequate increase of GFAP and GFAP gene transcripts. Although GFAP is an accepted marker for neurotoxicity, our data suggest the marker function of GFAP to be restricted to postnatal toxic insult.
星形胶质细胞的细胞骨架成分，即胶质纤维酸性蛋白（GFAP），是成熟大脑中神经毒性作用普遍认可的敏感指标。我们将GFAP用作与不同发育时期慢性低水平铅暴露相关的大鼠海马结构变化的标志物。研究了四组大鼠：对照组、围产期组（在大脑发育期间即E0 - P16暴露）、永久性组（在大脑发育期间及之后即E0 - P100暴露）和断奶后组（在大脑发育之后即P16 - P100暴露）。对切片进行了光学显微镜检查（苏木精 - 伊红染色、尼氏染色、过碘酸希夫染色（PAS）和GFAP特异性免疫组织化学）、电子显微镜检查和原位杂交（GFAP）。切片取自经过主动回避学习（AAL）和长时程增强（LTP）测试的动物。当铅暴露在大脑发育之后开始时（断奶后组），通过LTP和AAL评估，慢性铅暴露未影响胶质细胞和神经元功能。在该组中，星形胶质细胞的GFAP和GFAP基因转录水平升高。然而，当中毒发生在大脑发育时期（围产期和永久性组）时，铅暴露影响了神经元和胶质细胞功能。在这些组中，LTP和AAL受损，并且星形胶质细胞未能通过适当增加GFAP和GFAP基因转录本来对毒性暴露做出反应。尽管GFAP是公认的神经毒性标志物，但我们的数据表明GFAP的标志物功能仅限于出生后的毒性损伤。
