CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus
CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus
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DOI：
10.1016/j.ajpath.2018.10.020
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发表时间：
2019-02-01
影响因子：
6
通讯作者：
Czeisler, Catherine M.
中科院分区：
文献类型：
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作者：
Alves, Michele J.;Goksel, Mustafa;Czeisler, Catherine M.
文献中越来越多的证据表明，RNA RNA 结合蛋白聚集会扰乱神经元稳态，并导致与正常衰老和痴呆相关的症状。成年神经元中细胞周期蛋白 A2 的特异性消融会导致神经元多核糖体聚集以及学习和记忆缺陷。对老年小鼠的详细组织学和超微结构分析表明，有丝分裂后海马锥体神经元维持细胞周期蛋白 A2 表达，并且齿状颗粒下区的增殖细胞表达细胞周期蛋白 A2。神经发育早期细胞周期蛋白 A2 的缺失会通过规范/细胞周期机制抑制海马发育，包括延长胚胎海马祖细胞的细胞周期时间。然而，在成熟神经元中，细胞周期蛋白 A2 与树突 rRNA 共定位。成年海马中的细胞周期蛋白 A2 消融导致海马突触密度降低以及树突轴中 rRNA 颗粒的积累。我们得出的结论是，细胞周期蛋白 A2 以非规范/非细胞周期调节作用发挥作用，以维持成人锥体神经元核稳态。
Mounting evidence in the literature suggests that RNA RNA binding protein aggregations can disturb neuronal homeostasis and lead to symptoms associated with normal aging as well as dementia. The specific ablation of cyclin A2 in adult neurons results in neuronal polyribosome aggregations and learning and memory deficits. Detailed histologic and ultrastructural assays of aged mice revealed that post-mitotic hippocampal pyramidal neurons maintain cyclin A2 expression and that proliferative cells in the dentate subgranular zone express cyclin A2. Cyclin A2 loss early during neural development inhibited hippocampal development through canonical/cell-cycle mechanisms, including prolonged cell cycle timing in embryonic hippocampal progenitor cells. However, in mature neurons, cyclin A2 colocalized with dendritic rRNA. Cyclin A2 ablation in adult hippocampus resulted in decreased synaptic density in the hippocampus as well as in accumulation of rRNA granules in dendrite shafts. We conclude that cyclin A2 functions in a noncanonical/non cell cycle regulatory role to maintain adult pyramidal neuron ribostasis.