Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model.

Journal of Neuroinflammation
Xiao-Hui TangJian-Jun Yang

Abstract

A subanesthetic dose of ketamine provides rapid and effective antidepressant effects, but the molecular mechanism remains elusive. It has been reported that overactivation of extrasynaptic GluN2B receptors is associated with the antidepressant effects of ketamine and the interaction between GluN2B and calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) is important for GluN2B localization and activity. Here, we tested whether changes of CaMKIIα and GluN2B are involved in the antidepressant effects of ketamine. Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into male C57BL/6 mice. For the interventional study, mice were administrated with ketamine (10 mg/kg, i.p.) or a CaMKIIα inhibitor KN93. Behavioral alterations were evaluated by open-field, novelty-suppressed feeding, and forced-swimming tests. Physiological functions were evaluated by the body weight and fur coat state of mice. The levels of p-CaMKIIα, CaMKIIα, p-GluN2B, GluN2B, p-CREB, CREB, BDNF, GluR1, and GluR2 in the hippocampus were detected by western blotting. The interaction between GluN2B and CaMKIIα was studied using immunoprecipitation assay and small interfering RNA (siRNA) assays. The colocalizations of GluN2B/PSD95 and p-GluN2B/PSD95 wer...Continue Reading

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Citations

Nov 14, 2020·International Journal of Molecular Sciences·Malwina LisekTomasz Boczek
Apr 27, 2021·Pharmacology & Therapeutics·Cong-Yuan XiaWei-Ku Zhang
May 1, 2021·International Journal of Molecular Sciences·Kinga SałaciakKarolina Pytka

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Methods Mentioned

BETA
protein assay
transfection
confocal scanning microscopy
Immunoprecipitation

Software Mentioned

SPSS
GraphPad Prism
Image J

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