Lynx1 supports neuronal health in the mouse dorsal striatum during aging: an ultrastructural investigation.
Lynx1 supports neuronal health in the mouse dorsal striatum during aging: an ultrastructural investigation.
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DOI：
10.1007/s12031-014-0352-1
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Miwa JM
中科院分区：
文献类型：
--
作者：
Kobayashi A;Parker RL;Wright AP;Brahem H;Ku P;Oliver KM;Walz A;Lester HA;Miwa JM
烟碱型乙酰胆碱受体已被证明参与衰老大脑的神经保护。Lynx蛋白调节剂通过与烟碱受体直接相互作用来抑制胆碱能系统的活性。尽管Lynx1缺失突变小鼠表现出增强的学习能力和可塑性，但随着年龄的增长，它们在背侧纹状体也表现出宏观的空泡化，这在光学显微镜水平上是可以检测到的。尽管lynx1基因与大脑功能有关，但人们对这些与年龄相关的变化的细胞超微结构知之甚少。在这项研究中，我们使用光学和透射电子显微镜评估了1、3、7和13个月大的小鼠背侧纹状体的变性。我们观察到13个月大的Lynx1缺陷型纹状体神经纤维丢失，神经纤维束断裂，神经元核丢失。高倍镜下，这些神经纤维显示细胞内空泡和无序的髓鞘。这些形态变化很少或没有出现在较年轻的lynx1缺失突变小鼠中，或者在任何年龄的杂合子lynx1缺失突变小鼠中。这些数据表明，可以通过滴定lynx1的剂量来维持神经元的健康，并且lynx1基因可能参与了神经保护和增强学习之间的权衡。
Nicotinic acetylcholine receptors have been shown to participate in neuroprotection in the aging brain. Lynx protein modulators dampen the activity of the cholinergic system through direct interaction with nicotinic receptors. Although lynx1 null mutant mice exhibit augmented learning and plasticity, they also exhibit macroscopic vacuolation in the dorsal striatum as they age, detectable at the optical microscope level. Despite the relevance of the lynx1 gene to brain function, little is known about the cellular ultrastructure of these age-related changes. In this study, we assessed degeneration in the dorsal striatum in 1-, 3-, 7-, and 13-month-old mice, using optical and transmission electron microscopy. We observed a loss of nerve fibers, a breakdown in nerve fiber bundles, and loss of neuronal nuclei in the 13-month-old lynx1 null striatum. At higher magnification, these nerve fibers displayed intracellular vacuoles and disordered myelin sheaths. Few or none of these morphological alterations were present in younger lynx1 null mutant mice, or in heterozygous lynx1 null mutant mice at any age. These data indicate that neuronal health can be maintained by titrating lynx1 dosage, and that the lynx1 gene may participate in a trade-off between neuroprotection and augmented learning.
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影响因子：
2.9
作者：
Kaneko, S;Maeda, T;Kimura, J
通讯作者：
Kimura, J
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW
影响因子：
4.7
作者：
Orr-Urtreger, A;Broide, RS;Patrick, JW
通讯作者：
Patrick, JW
影响因子：
16.2
作者：
Miwa JM;Freedman R;Lester HA
通讯作者：
Lester HA
DOI：
10.1016/s1054-3589(08)60072-1
发表时间：
1997-01-01
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
Colquhoun, L M;Patrick, J W
通讯作者：
Patrick, J W