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p15INK4b regulates cell cycle signaling in hippocampal astrocytes of aged rats

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Abstract

Background and aims

Cyclin-dependent kinase inhibitor p15INK4b is thought to be an important player in regulating astrocytic cell cycle. However, little is known with regard to the expression of p15INK4b and its function in hippocampal astrocytes. This study evaluated the expression of p15INK4b and its function during different development stages in hippocampal astrocytes.

Methods

In this study, we cultured hippocampal astrocytes from neonatal adult and aged rats. The expression of p15INK4b in neonatal, adult and aged astrocytes was examined. Short interfering RNA (siRNA) was then used to study the functional effects of p15INK4b down-regulation during cell cycle regulation.

Results

We found the expression of p15INK4b in hippocampal astrocytes was detectable on postnatal day 7, was expressed at moderate levels in adult mice (9 months old) astrocytes and peaked in aged rat (24 months old) astrocytes. Incubation with siRNA significantly suppressed p15INK4b expression at the mRNA and protein levels in astrocytes. Down-regulation of p15INK4b increased [3H]-thymidine incorporation into DNA and allowed cells to pass the G0/G1-S checkpoint in aged but not in neonatal or adult astrocytes.

Conclusions

These observations suggest p15INK4b is expressed at a steady level in neonatal and adult rat hippocampal astrocytes with no effect on cell cycle regulation. Importantly, aged astrocyte cell cycle regulation was significantly affected by high expression levels of p15INK4b suggesting a role for p15INK4b in cell cycle regulation when it is expressed at high but not moderate or low levels in hippocampal astrocytes.

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Acknowledgments

We deeply thank Dr. Alyssa Charrier for critical reading and professional revision of our manuscript.

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Authors and Affiliations

  1. Department of Neurology, The Central Hospital of Wuhan, 26 Shengli Street, Wuhan, 430014, China

    Fang Wang & Linhong Zhang

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  1. Fang Wang
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  2. Linhong Zhang
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Correspondence to Fang Wang.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Informed consent was obtained from all individual participants included in the study.

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Wang, F., Zhang, L. p15INK4b regulates cell cycle signaling in hippocampal astrocytes of aged rats. Aging Clin Exp Res 28, 813–821 (2016). https://doi.org/10.1007/s40520-015-0484-3

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