Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

Ko Miyoshi, Kyosuke Kasahara, Ikuko Miyazaki, Masato Asanuma

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li2CO3 were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

Original languageEnglish
Pages (from-to)757-762
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume388
Issue number4
DOIs
Publication statusPublished - Oct 30 2009

Keywords

  • Bipolar mood disorder
  • Lithium
  • Melanin-concentrating hormone
  • Primary cilia

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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