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Publication : CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus.

First Author  Alves MJ Year  2019
Journal  Am J Pathol Volume  189
Issue  2 Pages  426-439
PubMed ID  30579783 Mgi Jnum  J:270514
Mgi Id  MGI:6276447 Doi  10.1016/j.ajpath.2018.10.020
Citation  Alves MJ, et al. (2019) CCNA2 Ablation in Aged Mice Results in Abnormal rRNA Granule Accumulation in Hippocampus. Am J Pathol 189(2):426-439
abstractText  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.
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