Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death

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.

Decrease in plasma adiponectin level and increase in adiponectin immunoreactivity in cortex and hippocampus after traumatic brain injury in rats

“…Therefore, we hypothesize that increased TNF-α expression might be one of the mechanisms responsible for the decrease in the plasma adiponectin level after TBI that was observed in the present study. Several authors have reported a high level of adiponectin immunoreactivity in the ischemic hemisphere in mice (20,24), whereas adiponectin mRNA was not detected in the brain (24). Taken together with these past results, our data suggest that the immunoreactivity of adiponectin in the brain reflects not the production, but the accumulation, in the injured brain (24).…”

Oxidative stress – assassin behind the ischemic stroke

“…Recent studies have discovered that the levels of the hormone adiponectin increase after ischemic stroke. Adiponectin is involved in the pro-apoptotic signalling cascade involving p38 mitogen-activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK) [84].…”

Characterization and Transcriptional Regulation Analysis of the Porcine PAQR6 Gene

“…surface adiponectin receptor, ADR1 can be activated by adiponectin and mediate the majority of the known biological actions of adiponectin such as regulation of energy homeostasis, glucose, and lipid metabolism (Yamauchi et al, 2002;Kadowaki et al, 2006;Thundyil et al, 2010). Adiponectin also regulates fatty acid oxidation by sequential activation of AMP-activated protein kinase, p38 mitogenactivated protein kinase, and peroxisome proliferatoractivated receptor alpha (Yoon et al, 2006).…”