Abnormal Mitosis in Reactive Astrocytes

Overview

Journal Acta Neuropathol Commun

Publisher Biomed Central

Specialty Neurology

Date 2020 Apr 16

PMID 32293551

Citations 9

Authors

Alexander Sosunov

Xiaoping Wu

Robert McGovern

Charles Mikell

Guy M McKhann 2nd

James E Goldman

Affiliations

Soon will be listed here.

Abstract

Although abnormal mitosis with disarranged metaphase chromosomes or many micronuclei in astrocytes (named "Alzheimer I type astrocytes" and later "Creutzfeldt-Peters cells") have been known for nearly 100 years, the origin and mechanisms of this pathology remain elusive. In experimental brain insults in rats, we show that abnormal mitoses that are not followed by cytokinesis are typical for reactive astrocytes. The pathology originates due to the inability of the cells to form normal mitotic spindles with subsequent metaphase chromosome congression, which, in turn may be due to shape constraints aggravated by cellular enlargement and to the accumulation of large amounts of cytosolic proteins. Many astrocytes escape from arrested mitosis by producing micronuclei. These polyploid astrocytes can survive for long periods of time and enter into new cell cycles.

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References

di Pietro F, Echard A, Morin X . Regulation of mitotic spindle orientation: an integrated view. EMBO Rep. 2016; 17(8):1106-30. PMC: 4967962. DOI: 10.15252/embr.201642292. View

Castedo M, Perfettini J, Roumier T, Andreau K, Medema R, Kroemer G . Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004; 23(16):2825-37. DOI: 10.1038/sj.onc.1207528. View

Eyers P, Maller J . Regulating the regulators: Aurora A activation and mitosis. Cell Cycle. 2003; 2(4):287-9. View

Pekny M, Pekna M . Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev. 2014; 94(4):1077-98. DOI: 10.1152/physrev.00041.2013. View

Mocco J, Shelton C, Sergot P, Ducruet A, Komotar R, Otten M . O-desulfated heparin improves outcome after rat cerebral ischemia/reperfusion injury. Neurosurgery. 2007; 61(6):1297-303. DOI: 10.1227/01.neu.0000306109.55174.e6. View

Garzon-Coral C, Fantana H, Howard J . A force-generating machinery maintains the spindle at the cell center during mitosis. Science. 2016; 352(6289):1124-7. PMC: 6535051. DOI: 10.1126/science.aad9745. View

Sofroniew M, Vinters H . Astrocytes: biology and pathology. Acta Neuropathol. 2009; 119(1):7-35. PMC: 2799634. DOI: 10.1007/s00401-009-0619-8. View

Lin T, Neuner A, Schiebel E . Targeting of γ-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol. 2014; 25(5):296-307. DOI: 10.1016/j.tcb.2014.12.002. View

Doxsey S . Re-evaluating centrosome function. Nat Rev Mol Cell Biol. 2001; 2(9):688-98. DOI: 10.1038/35089575. View

10.

Zhang R, Roostalu J, Surrey T, Nogales E . Structural insight into TPX2-stimulated microtubule assembly. Elife. 2017; 6. PMC: 5679754. DOI: 10.7554/eLife.30959. View

11.

Rieder C . Mitosis in vertebrates: the G2/M and M/A transitions and their associated checkpoints. Chromosome Res. 2011; 19(3):291-306. DOI: 10.1007/s10577-010-9178-z. View

12.

Morton A, Leavens W . Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res Bull. 2000; 52(1):51-9. DOI: 10.1016/s0361-9230(00)00238-0. View

13.

Houck S, Clark J . Dynamic subunit exchange and the regulation of microtubule assembly by the stress response protein human alphaB crystallin. PLoS One. 2010; 5(7):e11795. PMC: 2909917. DOI: 10.1371/journal.pone.0011795. View

14.

Kitagawa M, Lee S . The chromosomal passenger complex (CPC) as a key orchestrator of orderly mitotic exit and cytokinesis. Front Cell Dev Biol. 2015; 3:14. PMC: 4350427. DOI: 10.3389/fcell.2015.00014. View

15.

Nakayama Y, Soeda S, Ikeuchi M, Kakae K, Yamaguchi N . Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced Oncogenesis. Int J Mol Sci. 2017; 18(4). PMC: 5412395. DOI: 10.3390/ijms18040811. View

16.

Chou E, Hung L, Tang C, Hsu W, Wu H, Liao P . Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis. Cell Rep. 2016; 14(12):2975-87. DOI: 10.1016/j.celrep.2016.02.085. View

17.

Ganem N, Godinho S, Pellman D . A mechanism linking extra centrosomes to chromosomal instability. Nature. 2009; 460(7252):278-82. PMC: 2743290. DOI: 10.1038/nature08136. View

18.

Ma K . Alzheimer-type I astrogliopathy (AIA) and its implications for dynamic plasticity of astroglia: a historical review of the significance of AIA. J Neuropathol Exp Neurol. 2001; 60(2):121-31. DOI: 10.1093/jnen/60.2.121. View

19.

Loffler H, Fechter A, Matuszewska M, Saffrich R, Mistrik M, Marhold J . Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Res. 2011; 71(6):2129-39. DOI: 10.1158/0008-5472.CAN-10-2684. View

20.

Foley E, Kapoor T . Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol. 2012; 14(1):25-37. PMC: 3762224. DOI: 10.1038/nrm3494. View