Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

Mohammad Ejaz Ahmed; Yan Dong; Yujiao Lu; Donovan Tucker; Ruimin Wang; Quanguang Zhang

doi:10.1007/s12031-016-0830-8

Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

Mohammad Ejaz Ahmed, Yan Dong, Yujiao Lu, Donovan Tucker, Ruimin Wang, Quanguang Zhang

Neuroscience and Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Aberrant calcium influx is a common feature following ischemic reperfusion (I/R) in transient global cerebral ischemia (GCI) and causes delayed neuronal cell death in the CA1 region of the hippocampus. Activation of calcium-calmodulin (CaM)-dependent protein kinase IIα (CaMKIIα) is a key event in calcium signaling in ischemic injury. The present study examined the effects of intracerebroventricular (icv) injection of tatCN21 in ischemic rats 3 h after GCI reperfusion. Cresyl violet and NeuN staining revealed that tatCN21 exerted neuroprotective effects against delayed neuronal cell death of hippocampal CA1 pyramidal neurons 10 days post-GCI. In addition, TatCN21 administration ameliorated GCI-induced spatial memory deficits in the Barnes maze task as well as anxiety-like behaviors and spontaneous motor activity in the elevated plus maze and open field test, respectively. Mechanistic studies showed that the administration of tatCN21 decreased GCI-induced phosphorylation, translocation, and membrane targeting of CaMKIIα. Treatment with tatCN21 also inhibited the level of CaMKIIα-NR2B interaction and NR2B phosphorylation. Our results revealed an important role of tatCN21 in inhibiting CaMKIIα activation and its beneficial effects in neuroprotection and memory preservation in an ischemic brain injury model.

Original language	English (US)
Pages (from-to)	42-51
Number of pages	10
Journal	Journal of Molecular Neuroscience
Volume	61
Issue number	1
DOIs	https://doi.org/10.1007/s12031-016-0830-8
State	Published - Jan 1 2017

Keywords

CaMKIIα
Global cerebral ischemia
Hippocampus
NR2B
TatCN21

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

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10.1007/s12031-016-0830-8

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title = "Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia",

abstract = "Aberrant calcium influx is a common feature following ischemic reperfusion (I/R) in transient global cerebral ischemia (GCI) and causes delayed neuronal cell death in the CA1 region of the hippocampus. Activation of calcium-calmodulin (CaM)-dependent protein kinase IIα (CaMKIIα) is a key event in calcium signaling in ischemic injury. The present study examined the effects of intracerebroventricular (icv) injection of tatCN21 in ischemic rats 3 h after GCI reperfusion. Cresyl violet and NeuN staining revealed that tatCN21 exerted neuroprotective effects against delayed neuronal cell death of hippocampal CA1 pyramidal neurons 10 days post-GCI. In addition, TatCN21 administration ameliorated GCI-induced spatial memory deficits in the Barnes maze task as well as anxiety-like behaviors and spontaneous motor activity in the elevated plus maze and open field test, respectively. Mechanistic studies showed that the administration of tatCN21 decreased GCI-induced phosphorylation, translocation, and membrane targeting of CaMKIIα. Treatment with tatCN21 also inhibited the level of CaMKIIα-NR2B interaction and NR2B phosphorylation. Our results revealed an important role of tatCN21 in inhibiting CaMKIIα activation and its beneficial effects in neuroprotection and memory preservation in an ischemic brain injury model.",

keywords = "CaMKIIα, Global cerebral ischemia, Hippocampus, NR2B, TatCN21",

author = "Ahmed, {Mohammad Ejaz} and Yan Dong and Yujiao Lu and Donovan Tucker and Ruimin Wang and Quanguang Zhang",

note = "Funding Information: This study was supported by Research Grant NS086929 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA, and the American Heart Association Grant-in-Aid 15GRNT25240004. Publisher Copyright: {\textcopyright} 2016, Springer Science+Business Media New York.",

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T1 - Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

AU - Ahmed, Mohammad Ejaz

AU - Dong, Yan

AU - Lu, Yujiao

AU - Tucker, Donovan

AU - Wang, Ruimin

AU - Zhang, Quanguang

N1 - Funding Information: This study was supported by Research Grant NS086929 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA, and the American Heart Association Grant-in-Aid 15GRNT25240004. Publisher Copyright: © 2016, Springer Science+Business Media New York.

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N2 - Aberrant calcium influx is a common feature following ischemic reperfusion (I/R) in transient global cerebral ischemia (GCI) and causes delayed neuronal cell death in the CA1 region of the hippocampus. Activation of calcium-calmodulin (CaM)-dependent protein kinase IIα (CaMKIIα) is a key event in calcium signaling in ischemic injury. The present study examined the effects of intracerebroventricular (icv) injection of tatCN21 in ischemic rats 3 h after GCI reperfusion. Cresyl violet and NeuN staining revealed that tatCN21 exerted neuroprotective effects against delayed neuronal cell death of hippocampal CA1 pyramidal neurons 10 days post-GCI. In addition, TatCN21 administration ameliorated GCI-induced spatial memory deficits in the Barnes maze task as well as anxiety-like behaviors and spontaneous motor activity in the elevated plus maze and open field test, respectively. Mechanistic studies showed that the administration of tatCN21 decreased GCI-induced phosphorylation, translocation, and membrane targeting of CaMKIIα. Treatment with tatCN21 also inhibited the level of CaMKIIα-NR2B interaction and NR2B phosphorylation. Our results revealed an important role of tatCN21 in inhibiting CaMKIIα activation and its beneficial effects in neuroprotection and memory preservation in an ischemic brain injury model.

AB - Aberrant calcium influx is a common feature following ischemic reperfusion (I/R) in transient global cerebral ischemia (GCI) and causes delayed neuronal cell death in the CA1 region of the hippocampus. Activation of calcium-calmodulin (CaM)-dependent protein kinase IIα (CaMKIIα) is a key event in calcium signaling in ischemic injury. The present study examined the effects of intracerebroventricular (icv) injection of tatCN21 in ischemic rats 3 h after GCI reperfusion. Cresyl violet and NeuN staining revealed that tatCN21 exerted neuroprotective effects against delayed neuronal cell death of hippocampal CA1 pyramidal neurons 10 days post-GCI. In addition, TatCN21 administration ameliorated GCI-induced spatial memory deficits in the Barnes maze task as well as anxiety-like behaviors and spontaneous motor activity in the elevated plus maze and open field test, respectively. Mechanistic studies showed that the administration of tatCN21 decreased GCI-induced phosphorylation, translocation, and membrane targeting of CaMKIIα. Treatment with tatCN21 also inhibited the level of CaMKIIα-NR2B interaction and NR2B phosphorylation. Our results revealed an important role of tatCN21 in inhibiting CaMKIIα activation and its beneficial effects in neuroprotection and memory preservation in an ischemic brain injury model.

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Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

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