Grimes L, McGinty J, McLain P, Mitchell C, Tilson H, Hong J
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514.
J Neurosci. 1988 Jan;8(1):256-64. doi: 10.1523/JNEUROSCI.08-01-00256.1988.
The purpose of this study was to determine the role that dentate granule cells play in wet dog shakes (WDS), behavioral seizures, and hippocampal cell loss caused by systemic administration of kainic acid (KA). Rats were given bilateral injections of colchicine (COL) into the hippocampal formation to selectively lesion dentate granule cells. Two weeks later, they were injected subcutaneously with KA and were observed for WDS and seizures. Seizures were terminated with pentobarbital 2.5 hr after KA injection, and the rats were killed 48 hr later. The integrity of hippocampal cell populations and projections to the hippocampal formation from entorhinal cortex was assessed with radioimmunoassay and immunostaining for methionine-enkephalin (ME) and dynorphin (DYN) A, as well as with Timm and Nissl staining. Results indicate that COL injections eliminated KA-induced WDS, did not affect the latency to onset of seizures, and potentiated KA-induced cell loss in the CA3 region of hippocampus. COL lesions eliminated ME and DYN immunostaining of granule cells, but not ME immunostaining of entorhinal afferents to the dentate gyrus or Ammon's horn. These findings indicate that granule cells are an essential neuronal link in the expression of KA-induced WDS, but that seizures propagate along other pathways in the limbic system.
本研究的目的是确定齿状颗粒细胞在湿狗颤抖(WDS)、行为性癫痫发作以及由全身注射 kainic 酸(KA)引起的海马细胞丢失中所起的作用。给大鼠双侧海马结构注射秋水仙碱(COL)以选择性损伤齿状颗粒细胞。两周后,给它们皮下注射 KA,并观察其 WDS 和癫痫发作情况。注射 KA 后 2.5 小时用戊巴比妥终止癫痫发作,48 小时后处死大鼠。用放射免疫测定法以及对甲硫氨酸脑啡肽(ME)和强啡肽(DYN)A 进行免疫染色,同时结合 Timm 和 Nissl 染色,评估海马细胞群的完整性以及内嗅皮质向海马结构的投射。结果表明,注射 COL 消除了 KA 诱导的 WDS,不影响癫痫发作的起始潜伏期,并且增强了 KA 诱导的海马 CA3 区细胞丢失。COL 损伤消除了颗粒细胞的 ME 和 DYN 免疫染色,但未消除内嗅传入齿状回或海马角的 ME 免疫染色。这些发现表明,颗粒细胞是 KA 诱导的 WDS 表达中必不可少的神经元环节,但癫痫发作沿边缘系统的其他途径传播。