Stimulation of the Sigma-1 Receptor and the Effects on Neurogenesis and Depressive Behaviors in Mice

  • Kohji FukunagaEmail author
  • Shigeki Moriguchi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 964)


Sigma-1 receptor (Sig-1R) is molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to mitochondria. Recent studies show that Sig-1R stimulation antagonizes depressive-like behaviors in animal models, but molecular mechanisms underlying this effect remain unclear. Here, we focus on the effects of Sig-1R ligands on hippocampal neurogenesis and depressive-like behaviors. Sig-1R stimulation also enhances CaMKII /CaMKIV and protein kinase B (Akt) activities in hippocampus. Therefore, we discuss the fundamental roles of Sig-1R, CaMKII /CaMKIV and protein kinase B (Akt) signaling in amelioration of depressive-like behaviors following Sig-1R stimulation.


CaMKII CaMKIV BDNF Neurogenesis Depression Sigma-1 receptor 



protein kinase B


brain-derived neurotrophic factor




calcium/calmodulin-dependent protein kinase II


calcium/calmodulin-dependent protein kinase IV


cAMP-responsive element binding protein


dentate gyrus




endoplasmic/sacroplasmic reticulum


extracellular signal-regulated kinase


long-term potentiation


N-methyl-D-aspartate receptor


sarcoplasmic/endoplasmic Ca2+-ATPase


sigma-1 receptor


selective serotonin reuptake inhibitors


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© Springer International Publishing AG (outside the USA) 2017

Authors and Affiliations

  1. 1.Department of Pharmacology, Graduate School of Pharmaceutical SciencesTohoku UniversitySendaiJapan

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