Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death

Thundyil, John, Tang, Sung-Chun, Okun, Eitan, Shah, Kausik, Karamyan, Vardan T., Li , Yu-I, Woodruff, Trent M., Taylor, Stephen M., Jo, Dong-Gyu, Mattson, Mark P and Arumugam, Thiruma V. (2010) Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death. Experimental and Translational Stroke Medicine, 2 1: 15-1-15-8. doi:10.1186/2040-7378-2-15


Author Thundyil, John
Tang, Sung-Chun
Okun, Eitan
Shah, Kausik
Karamyan, Vardan T.
Li , Yu-I
Woodruff, Trent M.
Taylor, Stephen M.
Jo, Dong-Gyu
Mattson, Mark P
Arumugam, Thiruma V.
Title Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death
Journal name Experimental and Translational Stroke Medicine   Check publisher's open access policy
ISSN 2040-7378
Publication date 2010-08-11
Sub-type Article (original research)
DOI 10.1186/2040-7378-2-15
Open Access Status DOI
Volume 2
Issue 1
Start page 15-1
End page 15-8
Total pages 8
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2011
Language eng
Formatted abstract
Background: Adiponectin is a hormone produced in and released from adipose cells, which has been shown to have anti-diabetic and anti-inflammatory actions in peripheral cells. Two cell surface adiponectin receptors (ADRs) mediate the majority of the known biological actions of adiponectin. Thus far, ADR expression in the brain has been demonstrated in the arcuate and the paraventricular nucleus of hypothalamus, where its activation affects food intake. Recent findings suggest that levels of circulating adiponectin increase after an ischemic stroke, but the role of adiponectin receptor activation in stroke pathogenesis and its functional outcome is unclear.

Methods: Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion. Primary cortical neuronal cultures were established from individual embryonic neocortex. For glucose deprivation (GD), cultured neurons were incubated in glucose-free Locke's medium for 6, 12 or 24 h. For combined oxygen and glucose deprivation (OGD), neurons were incubated in glucose-free Locke's medium in an oxygen-free chamber with 95% N2/5% CO2 atmosphere for either 3, 6, 9, 12 or 24 h. Primary neurons and brain tissues were analysed for Adiponectin and ADRs using reverse transcriptase polymerase chain reaction (RT-PCR), immunoblot and immunochemistry methods.

Results: Cortical neurons express ADR1 and ADR2, and that the levels of ADR1 are increased in neurons in response to in vitro or in vivo ischemic conditions. Neurons treated with either globular or trimeric adiponectin exhibited increased vulnerability to oxygen and glucose deprivation which was associated with increased activation of a pro-apoptotic signaling cascade involving p38 mitogen-activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK).

Conclusions: This study reveals a novel pathogenic role for adiponectin and adiponectin receptor activation in ischemic stroke. We show that cortical neurons express ADRs and reveal a pro-apoptotic role for ADR1 activation in neurons, which may render them vulnerable to ischemic death.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number 15

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Thu, 10 Feb 2011, 16:43:22 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences