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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)42-51
Number of pages10
JournalJournal of Molecular Neuroscience
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Protein Kinase Inhibitors
Brain Ischemia
Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Peptides
Reperfusion
Cell Death
Phosphorylation
Calcium-Calmodulin-Dependent Protein Kinases
Calcium Signaling
Pyramidal Cells
Transient Ischemic Attack
Memory Disorders
Neuroprotective Agents
Brain Injuries
Hippocampus
Motor Activity
Anxiety
Staining and Labeling
Calcium

Keywords

  • CaMKIIα
  • Global cerebral ischemia
  • Hippocampus
  • NR2B
  • TatCN21

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia. / Ahmed, Mohammad Ejaz; Dong, Yan; Lu, Yujiao; Tucker, Donovan; Wang, Ruimin; Zhang, Quanguang.

In: Journal of Molecular Neuroscience, Vol. 61, No. 1, 01.01.2017, p. 42-51.

Research output: Contribution to journalArticle

Ahmed, Mohammad Ejaz ; Dong, Yan ; Lu, Yujiao ; Tucker, Donovan ; Wang, Ruimin ; Zhang, Quanguang. / Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia. In: Journal of Molecular Neuroscience. 2017 ; Vol. 61, No. 1. pp. 42-51.
@article{e93084ad8a5e4a8f9827e65d0f98769c,
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",
year = "2017",
month = "1",
day = "1",
doi = "10.1007/s12031-016-0830-8",
language = "English (US)",
volume = "61",
pages = "42--51",
journal = "Journal of Molecular Neuroscience",
issn = "0895-8696",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

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

PY - 2017/1/1

Y1 - 2017/1/1

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.

KW - CaMKIIα

KW - Global cerebral ischemia

KW - Hippocampus

KW - NR2B

KW - TatCN21

UR - http://www.scopus.com/inward/record.url?scp=84986269064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986269064&partnerID=8YFLogxK

U2 - 10.1007/s12031-016-0830-8

DO - 10.1007/s12031-016-0830-8

M3 - Article

C2 - 27604243

AN - SCOPUS:84986269064

VL - 61

SP - 42

EP - 51

JO - Journal of Molecular Neuroscience

JF - Journal of Molecular Neuroscience

SN - 0895-8696

IS - 1

ER -