Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injury
Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injury
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DOI：
10.1002/hipo.20183
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发表时间：
2006-01-01
期刊：
影响因子：
3.5
通讯作者：
Cohen, A. S.
中科院分区：
文献类型：
--
作者：
Schwarzbach, E.;Bonislawski, D. P.;Cohen, A. S.
创伤性脑损伤（TBI）是一种严重的健康问题，通常会导致持久的认知缺陷，特别是记忆功能障碍。海马体，一个对学习和记忆至关重要的结构，在创伤性脑损伤中经常受损。由于长期增强（LTP）是学习和记忆的主要细胞模型，因此本研究采用外侧液体撞击损伤（FPI）来研究损伤如何影响小鼠CA1区LTP。FPI动物的脑切片显示，损伤后17天ca17区无法诱导LTP。然而，在损伤后7天，神经元CA1区可以被诱导长期抑制，这表明某些形式的突触可塑性仍然可以被激发。采用多学科方法，研究了无法诱导和维持CA1区LTP的潜在机制。该研究表明，损伤导致n -甲基- d -天冬氨酸电位和谷氨酸诱导的兴奋电流显著减少，树突棘大小增加，a-钙钙调蛋白激酶II的表达减少。这些发现可能是损伤引起的LTP缺乏的基础，因此，导致认知障碍通常与TBI相关。此外，这些结果为潜在的治疗干预提供了有吸引力的场所，旨在减轻人类创伤性脑损伤的破坏性后果。(c) 2006 Wiley-Liss, Inc。
Traumatic brain injury (TBI) is a significant health issue that often causes enduring cognitive deficits, in particular memory dysfunction. The hippocampus, a structure crucial in learning and memory, is frequently damaged during TBI. Since long-term potentiation (LTP) is the leading cellular model underlying learning and memory, this study was undertaken to examine how injury affects area CA1 LTP in mice using lateral fluid percussion injury (FPI). Brain slices derived from FPI animals demonstrated an inability to induce LTP in area CA1 7 days postinjury. However, area CA1 long-term depression could be induced in neurons 7 days postinjury, demonstrating that some forms of synaptic plasticity can still be elicited. Using a multidisciplined approach, potential mechanisms underlying the inability to induce and maintain area CA1 LTP were investigated. This study demonstrates that injury leads to significantly smaller N-methyl-D-aspartate potentials and glutamate-induced excitatory currents, increased dendritic spine size, and decreased expression of a-calcium calmodulin kinase II. These findings may underlie the injuryinduced lack of LTP and thus, contribute to cognitive impairments often associated with TBI. Furthermore, these results provide attractive sites for potential therapeutic intervention directed toward alleviating the devastating consequences of human TBI. (c) 2006 Wiley-Liss, Inc.