Lithium Inhibits GSK3β Activity via Two Different Signaling Pathways in Neurons After Spinal Cord Injury.

Abstract:

:Spinal cord injury (SCI) is a type of long-term disability with a high morbidity rate in clinical settings for which there is no effective clinical treatment to date. Usually, lithium is used as a popular mood stabilizer. Recently, growing evidence has shown that lithium has clear neuroprotective effects after SCI, and the administration of lithium can effectively improve locomotor recovery. However, the exact neuroprotective mechanism of lithium is still not understood. Glycogen synthase kinase-3 beta (GSK3β) is a serine/threonine kinase that plays an important role in the neuroprotective effects of lithium both in vivo and in vitro. In this study, we discovered that lithium inhibits GSK3β activity through two different signaling pathways in spinal cord neurons. In the acute phase, lithium inhibited GSK3β activity by stimulating phosphorylation of AKT; in the chronic phase, we first discovered that lithium additionally upregulated the expression of Na+, K+-ATPase α1 (NKA α1), which had an inhibitory effect on GSK3β activity by inducing the expression of glucocorticoid inducible kinase 1 (SGK1). SGK1 is well known as a regulator of the GSK3β/β-catenin signaling pathway. Moreover, the suppressed activity of GSK3β increased the level of β-catenin in the cytoplasm, which gave rise to the translocation of the freely stabilized β-catenin to the nucleus. In addition, the accumulation of β-catenin in the nucleus had the benefits of neuronal survival. Hopefully our findings from this study are beneficial in revealing the neuroprotective mechanism of lithium and in offering novel targets for the development of new SCI therapeutic drugs.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Li B,Ren J,Yang L,Li X,Sun G,Xia M

doi

10.1007/s11064-018-2488-9

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

848-856

issue

4

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-018-2488-9

journal_volume

43

pub_type

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