Cocaine promotes primary human astrocyte proliferation via JNK-dependent up-regulation of cyclin A2

Chun Ting Lee, Kristen L. Boeshore, Chun Wu, Kevin G. Becker, Stacie L. Errico, Deborah C Mash, William J. Freed

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Purpose: Astrocytes perform a plethora of important functions in the central nervous system (CNS) and are involved in cocaine-evoked synaptic plasticity. Previously, we showed that while cocaine decreased cyclin A2 expression in primary human neural progenitor cells, it increased cyclin A2 expression in human astrocytes. Since cyclin A2 is an essential regulator of the cell cycle, the aim of the present study is to clarify the effect of cocaine on proliferation of human astrocytes and elucidate the underlying molecular mechanisms. Methods: Primary human astrocytes were treated with either 1, 10, or 100 μM cocaine for 48 hr, and cell proliferation was measured using the CyQUANT cell proliferation assay. To elucidate the molecular mechanisms through which cocaine affects the proliferation of astrocytes, we analyzed gene expression profiles in cocaine-treated primary human astrocytes using a human focused cDNA array. Gene ontology/pathway enrichment analysis, STRING protein-protein interaction analysis, RT-qPCR, and western blotting were used to identify signal transduction pathways that are involved in cocaine-induced astrocyte dysfunction. Results: Cocaine at 10 and 100 μM significantly increased human astrocyte proliferation. Gene expression profiling revealed the JNK MAP kinase pathway as a driver of cell proliferation affected by cocaine in human astrocytes. Further experiments showed that cocaine-induced JNK activation induced up-regulation of cyclin A2, leading to enhanced proliferation of human astrocytes. Conclusion: Cocaine-induced abnormal increases in the number of astrocytes may cause disruption in neuron-glia signaling and contribute to synaptic impairment in the CNS. Understanding the mechanisms of cocaine's effects on human astrocytes may help to reveal the involvement of glial cells in addictive behaviors.

Original languageEnglish (US)
Pages (from-to)965-976
Number of pages12
JournalRestorative Neurology and Neuroscience
Volume34
Issue number6
DOIs
StatePublished - 2016

Keywords

  • addiction
  • Astrocytes
  • cocaine
  • cyclin A
  • JNK
  • reactive astrogliosis

ASJC Scopus subject areas

  • Medicine(all)
  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Cocaine promotes primary human astrocyte proliferation via JNK-dependent up-regulation of cyclin A2'. Together they form a unique fingerprint.

  • Cite this

    Lee, C. T., Boeshore, K. L., Wu, C., Becker, K. G., Errico, S. L., Mash, D. C., & Freed, W. J. (2016). Cocaine promotes primary human astrocyte proliferation via JNK-dependent up-regulation of cyclin A2. Restorative Neurology and Neuroscience, 34(6), 965-976. https://doi.org/10.3233/RNN-160676