Expression and role of CaMKII and Cx43 in a rat model of post‑stroke depression

Abstract

Expression of Ca 2+ /CaM-dependent protein kinase II (CaMKII) and connexin 43 (Cx43) in a rat model of post-stroke depression (PSD) was investigated. Rats were separated into control group (10 rats underwent a sham operation and were not ligated after incision), PSD group (13 PSD rats) and KN93 group (12 rats were treated with KN93, an inhibitor of CaMKII, on the basis of the PSD group). After PSD modeling, Longa scoring was performed, and an open field test as well as a step-through test were carried out to observe rat behavior. RT-qPCR and western blot analysis were used to detect the expression of CaMKII and CX43 in the hippocampus tissue. On the 14th day, the Longa scores in the PSD and KN93 groups were higher than that in the control group (P<0.05), while on the 18th day, Longa score was higher in the PSD group than that in the control and KN93 groups, and higher in the KN93 group than that in the control group (both P<0.05). In the PSD group, the Longa score on the 18th day was significantly higher than that on the 14th day, whereas in the KN93 group, the Longa score on the 18th day was significantly lower than that on the 14th day (both P<0.05). Compared with the PSD group on the 18th day, the passive avoidance defects in the KN93 group were improved, and the frequency of activity in the open field test was significantly increased. On the 18th day, the expression levels of the mRNA and protein of CaMKII were higher in the PSD group than in the control group, whereas those of Cx43 were lower in the PSD group than those in the control group (P<0.05). The mRNA and protein expression levels of CaMKII in the KN93 group were lower than those in the PSD group, but higher than those in the control group. In PSD rats, CaMKII expression is upregulated, but Cx43 expression is downregulated, and both CaMKII and Cx43 may participate in PSD. The inhibitor of CaMKII, KN93, can improve the depression in PSD rats.

A New Perspective on Hippocampal Synaptic Plasticity and Post-stroke Depression

“…These studies indicate that the Cx43 gap-junction protein and its pathway in the hippocampus can effectively alleviate depressive behavior induced by CUMS. Similarly, a decrease in Cx43 protein expression was observed in PSD rats (Tao et al 2019). Hippocampal Cx43 gap junctions play a considerable role in depression.…”

“…CaMKII not only regulates LTP but also participates in the development of LTD by acting on GluA1 Ser567 (Coultrap et al 2014). Tao et al found that CaMKII expression was upregulated in the hippocampus of PSD rats and that the CaMKII inhibitor KN93 improved depressive behavior in PSD (Tao et al 2019). By studying the antidepressant effects of two cyclic enol ether terpene compounds, Zhang et al found that combined treatment with both compounds rapidly inhibited CaMKII phosphorylation and enhanced BDNF signaling, whereas injection of a CaMKII activator attenuated its antidepressant effects and BDNF expression .…”

Inhibition of autophagy by CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR pathway contributes to ischemic postconditioning-induced neuroprotection against cerebral ischemia-reperfusion injury

“…Twenty-four hours following the sham/MCAO surgeries, rats were subjected to a neurological examination (Longa test) consisting of a six-point scale [ 33 ]: 0, no symptom; 1, Failure to extend left forepaw completely (shows mild focal neurological deficit); 2, circling/turning to one side while walking (moderate focal neurological deficit); 3, falling to one side while walking (indicates a severe focal neurological deficit); 4, loss of consciousness and no voluntary movement; and 5, death due to brain ischemia.…”

Single-cell RNA sequencing of peripheral blood reveals that monocytes with high cathepsin S expression aggravate cerebral ischemia–reperfusion injury

“…A gene was de ned as signi cantly associated with pseudotime if its estimated q value was lower than 0.01. Neurological de cit score Neurological de cits after 3 days of reperfusion in each mouse were evaluated with a 5-point scoring system using the Longa score test as previously described [24]. The scoring standards were as follows: 0 = no neurologic de cit; 1 = failure to extend the contralateral forepaw fully; 2 = circling to the contralateral side; 3 = falling over to the contralateral side; and 4 = no spontaneous locomotor activity.…”