Normal mitochondrial respiratory function is essential for spatial remote memory in mice
Normal mitochondrial respiratory function is essential for spatial remote memory in mice
复制标题
DOI：
10.1186/1756-6606-1-21
复制
发表时间：
2008-01-01
期刊：
影响因子：
3.6
通讯作者：
Hayashi, Jun-Ichi
中科院分区：
文献类型：
--
作者：
Tanaka, Daisuke;Nakada, Kazuto;Hayashi, Jun-Ichi
背景：在认知障碍患者中发现线粒体DNA （mtDNA）具有致病性突变。然而，关于致病性mtDNA突变和由此产生的线粒体呼吸缺陷是否有助于认知改变的表达，如学习和记忆障碍，人们知之甚少。为了解决这一点，我们使用了两组具有野生型和致病性缺失（Delta） mtDNA异质性的反线粒体小鼠（mito-小鼠）；“低”组携带50%或更少的Delta mtDNA，“高”组携带50%以上的Delta mtDNA。结果：两组在空间学习和短时保留延迟记忆方面均表现正常。mtDNA负荷不影响学习和时间记忆。然而，高智商组在长时间的记忆延迟中表现出严重的记忆损伤。在这些小鼠的视觉皮层和齿状回中，我们观察到线粒体呼吸缺陷，Ca2+/钙调素依赖性激酶ii - α (α - camkii)减少，这是一种对建立空间远程记忆很重要的蛋白质。结论：正常的线粒体呼吸功能是记忆痕迹保留和巩固的必要条件；由于高负荷的致病性突变mtDNA导致该功能的缺陷是导致空间远程记忆优先受损的原因。
Background: Mitochondrial DNA (mtDNA) with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice) with heteroplasmy for wild-type and pathogenically deleted (Delta) mtDNA; the "low" group carried 50% or less Delta mtDNA, and the "high" group carried more than 50% Delta mtDNA.Results: Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that.mtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-alpha (alpha-CaMKII), a protein important for the establishment of spatial remote memory.Conclusion: Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.