Morgan T E, Nichols N R, Pasinetti G M, Finch C E
Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Exp Neurol. 1993 Apr;120(2):291-301. doi: 10.1006/exnr.1993.1063.
This study examined TGF-beta 1 mRNA levels and cellular localization in the F344 rat hippocampus following deafferentation or kainic acid (KA)-induced neurodegeneration. By RNA solution hybridization, TGF-beta 1 transcripts were at low prevalence in intact adult rat hippocampus (0.02 pg/microgram total RNA). Four days after unilateral entorhinal cortex lesioning (ECL), TGF-beta 1 mRNA increased threefold in the ipsilateral hippocampus. This increase was localized to the outer molecular layer of the dentate gyrus, where gliosis, synapse loss, and synaptic reorganization occur. TGF-beta 1 mRNA also increased in the hippocampus after KA-induced limbic seizures, particularly in the areas of the hippocampus undergoing neurodegeneration. Microglia [OX-42 immunoreactive (IR) cells] responded to these two lesions with distinct morphological changes. Combined immunocytochemistry-in situ hybridization showed that TGF-beta 1 mRNA was localized to reactive microglia (OX-42-IR, with blunt processes), but not to resting ramified microglia (OX-42-IR, with numerous fine processes) or to astrocytes (GFAP-IR). After ECL, round macrophage-like cells (OX-42-IR with TGF-beta 1 mRNA) were seen at the wound site. Thus, brain macrophage/microglial cells produce TGF-beta 1 mRNA in the hippocampus in response to deafferentation and neurodegeneration.
本研究检测了去传入神经支配或 kainic 酸（KA）诱导的神经变性后 F344 大鼠海马中 TGF-β1 mRNA 水平及细胞定位。通过 RNA 溶液杂交，TGF-β1 转录本在完整成年大鼠海马中的丰度较低（0.02 pg/μg 总 RNA）。单侧内嗅皮质损伤（ECL）4 天后，同侧海马中 TGF-β1 mRNA 增加了三倍。这种增加定位于齿状回的外分子层，此处发生胶质增生、突触丢失和突触重组。KA 诱导边缘性癫痫发作后，海马中的 TGF-β1 mRNA 也增加，特别是在经历神经变性的海马区域。小胶质细胞[OX-42 免疫反应性（IR）细胞]对这两种损伤有不同的形态学变化。免疫细胞化学-原位杂交联合检测显示，TGF-β1 mRNA 定位于反应性小胶质细胞（OX-42-IR，有钝突），而不是静止的分支状小胶质细胞（OX-42-IR，有许多细突）或星形胶质细胞（GFAP-IR）。ECL 后，在伤口部位可见圆形巨噬细胞样细胞（OX-42-IR 且有 TGF-β1 mRNA）。因此，脑巨噬细胞/小胶质细胞在海马中响应去传入神经支配和神经变性而产生 TGF-β1 mRNA。
