Lithium Reversibly Inhibits Schwann Cell Proliferation and Differentiation Without Inducing Myelin Loss

Gonzalo Piñero, Randall Berg, Natalia Denise Andersen, Patricia Setton-Avruj, Paula V Monje

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

This study was undertaken to examine the bioactivity, specificity, and reversibility of lithium’s action on the growth, survival, proliferation, and differentiation of cultured Schwann cells (SCs). In isolated SCs, lithium promoted a state of cell cycle arrest that featured extensive cell enlargement and c-Jun downregulation in the absence of increased expression of myelin-associated markers. In addition, lithium effectively prevented mitogen-induced S-phase entry without impairing cell viability. When lithium was administered together with differentiating concentrations of cyclic adenosine monophosphate (cAMP) analogs, a dramatic inhibition of the expression of the master regulator of myelination Krox-20 was observed. Likewise, lithium antagonized the cAMP-dependent expression of various myelin markers such as protein zero, periaxin, and galactocerebroside and allowed SCs to maintain high levels of expression of immature SC markers even in the presence of high levels of cAMP and low levels of c-Jun. Most importantly, the inhibitory action of lithium on SC proliferation and differentiation was shown to be dose dependent, specific, and reversible upon removal of lithium compounds. In SC-neuron cultures, lithium suppressed myelin sheath formation while preserving axonal integrity, SC-axon contact, and basal lamina formation. Lithium was unique in its ability to prevent the onset of myelination without promoting myelin degradation or SC dedifferentiation. To conclude, our results underscored an unexpected antagonistic action of lithium on SC mitogenesis and myelin gene expression. We suggest that lithium represents an attractive pharmacological agent to safely and reversibly suppress the onset of SC proliferation, differentiation, and myelination while maintaining the integrity of pre-existing myelinated fibers.

Original languageEnglish (US)
Pages (from-to)1-21
Number of pages21
JournalMolecular Neurobiology
DOIs
StateAccepted/In press - Dec 5 2016

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Schwann Cells
Myelin Sheath
Lithium
Cell Differentiation
Cell Proliferation
Cyclic AMP
Lithium Compounds
Cell Dedifferentiation
Cell Enlargement
Cell Cycle Checkpoints
S Phase
Mitogens
Basement Membrane
Axons
Cultured Cells
Cell Survival
Down-Regulation
Cell Culture Techniques
Pharmacology
Gene Expression

Keywords

  • cAMP
  • Dedifferentiation
  • Krox-20
  • Lithium chloride
  • Myelination
  • Schwann cells

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Lithium Reversibly Inhibits Schwann Cell Proliferation and Differentiation Without Inducing Myelin Loss. / Piñero, Gonzalo; Berg, Randall; Andersen, Natalia Denise; Setton-Avruj, Patricia; Monje, Paula V.

In: Molecular Neurobiology, 05.12.2016, p. 1-21.

Research output: Contribution to journalArticle

Piñero, Gonzalo ; Berg, Randall ; Andersen, Natalia Denise ; Setton-Avruj, Patricia ; Monje, Paula V. / Lithium Reversibly Inhibits Schwann Cell Proliferation and Differentiation Without Inducing Myelin Loss. In: Molecular Neurobiology. 2016 ; pp. 1-21.
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