Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats

Neuropharmacology
Ningbo XuJohn H Zhang

Abstract

Adiponectin is an important adipocyte-derived plasma protein that has beneficial effects on cardio- and cerebrovascular diseases. A low level of plasma Adiponectin is associated with increased mortality post ischemic stroke; however, little is known about the causal role of Adiponectin as well as its molecular mechanisms in neonatal hypoxia ischemia (HI). In the present study, ten-day-old rat pups were subjected to right common carotid artery ligation followed by 2.5 h hypoxia. Recombinant human Adiponectin (rh-Adiponectin) was administered intranasally 1 h post HI. Adiponectin Receptor 1 (AdipoR1) siRNA, APPL1 siRNA, LKB1 siRNA were administered through intracerebroventricular injection 48 h before HI. Brain infarct area measurement, neurological function test, western blot, Fluoro Jade C (FJC), TUNEL, and immunofluorescence staining were conducted. Results revealed that endogenous Adiponectin, AdipoR1 and APPL1 were increased in a time dependent manner after HI. Administration of rh-Adiponectin reduced brain infarct area, neuronal apoptosis, brain atrophy and improved neurological function at 24 h and 4 weeks post HI. Furthermore, rh-Adiponectin treatment increased Adiponectin, AdipoR1, APPL1, cytosolic LKB1, p-AMPK expressio...Continue Reading

Citations

Oct 28, 2019·Chinese Medical Journal·Wen-Ze Xiao, Li Zhang
Feb 2, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mariko SaitoBhaskar C Das
Feb 16, 2020·International Journal of Molecular Sciences·Hyung Muk ChoiKyoung Soo Kim
Mar 11, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhenhua ZhouJohn H Zhang
Jun 25, 2019·Frontiers in Pharmacology·Bin LiuHaijing Yan
May 17, 2019·Neural Plasticity·Mariangela GennaroTommaso Pizzorusso
Jan 31, 2020·Oxidative Medicine and Cellular Longevity·Jing YuJohn H Zhang
May 1, 2021·International Journal of Molecular Sciences·Zuzanna Flis, Edyta Molik
Jul 3, 2021·Cells·Ivó H HernándezMaría José Pérez-Álvarez
Aug 17, 2021·Molecular Medicine Reports·Ruiying LiuDanfei Lou
Dec 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiankun TuSong-Sheng Shi

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