Febrile seizures impair memory and cAMP response-element binding protein activation
Febrile seizures impair memory and cAMP response-element binding protein activation
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DOI：
10.1002/ana.10789
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发表时间：
2003-12-01
影响因子：
11.2
通讯作者：
Huang, CC
中科院分区：
文献类型：
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作者：
Chang, YC;Huang, AM;Huang, CC
短暂但反复的发热性癫痫发作（FS）对记忆的长期影响尚未像单次和长时间癫痫发作对发育中的大脑的影响那样得到彻底的研究。使用加热空气FS范式，我们在产后10至12天对雄性大鼠幼仔进行1次、3次或9次短暂FS。在FS后72小时内没有海马神经元损伤或凋亡，也没有明显的海马神经元丢失，苔藓纤维异常发芽，或成年期任何FS组对戊四唑的癫痫发作阈值改变。然而，经过9次早期FS的成年大鼠，在Morris水迷宫中表现出长期记忆缺陷。在抑制性回避任务中，他们也表现出中期和长期记忆受损，但短期记忆没有受损。抑制回避训练3小时后，9 - fs组大鼠海马区cAMP反应元件结合蛋白（CREB）磷酸化水平明显低于对照组。此外，罗利普兰通过抑制IV型磷酸二酯酶激活cAMP-CREB信号通路，通过增强海马CREB磷酸化，逆转了9 - fs组大鼠的长期记忆缺陷。这些结果引起了人们对早期大脑发育中即使是短暂的频繁重复的FS的长期认知后果的关注。
The long-term effects of brief but repetitive febrile seizures (FS) on memory have not been as thoroughly investigated as the impact of single and prolonged seizure in the developing brain. Using a heated-air FS paradigm, we subjected male rat pups to one, three, or nine episodes of brief FS on days 10 to 12 postpartum. Neither hippocampal neuronal damage nor apoptosis was noted within 72 hours after FS, nor was there significant hippocampal neuronal loss, aberrant mossy fiber sprouting, or altered seizure threshold to pentylenetetrazol in any FS group at adulthood. The adult rats subjected to nine episodes of early-life FS, however, showed long-term memory deficits as assessed by the Morris water maze. They also exhibited impaired intermediate and long-term memory but spared short-term memory in the inhibitory avoidance task. Three hours after inhibitory avoidance training, phosphorylation of cAMP response-element binding (CREB) protein in the hippocampus was significantly lower in nine-FS-group rats than in controls. Furthermore, rolipram administration, which activated the cAMP-CREB signaling pathway by inhibiting phosphodiesterase type IV, reversed the long-term memory deficits in nine-FS-group rats by enhancing hippocampal CREB phosphorylation. These results raise concerns about the long-term cognitive consequences of even brief frequently repetitive FS during early brain development.