Gemfibrozil pretreatment resulted in a sexually dimorphic outcome | 48847

Journal of Neuroscience and Neuropharmacology

Gemfibrozil pretreatment resulted in a sexually dimorphic outcome in the rat models of global cerebral ischemia-reperfusion via modulation of mitochondrial pro-survival and apoptotic cell death factors as well as MAPKs

4th Global Experts Meeting on Neuropharmacology

September 14-16, 2016 San Antonio, USA

Leila Khalaj

Alborz University of Medical Sciences, Iran

Posters & Accepted Abstracts: Neurochem Neuropharm

Abstract :

Inducers of mitochondrial biogenesis are recently under investigation for use as a novel therapeutic approach in neurodegenerative disorders. Gemfibrozil, a fibrate, is clinically administered to control hyperlipidemia, and it secondarily prevents cardiovascular events such as cardiac arrest in susceptible patients. The ability of Gemfibrozil is investigated for the first time to modulate mitochondrial pro-survival factors involved in the mitochondrial biogenesis signaling pathway, including peroxisome proliferator-activated receptor coactivator-1?± (PGC-1?±), nuclear respiratory factor (NRF-1), and mitochondrial transcription factor A (TFAM) in the brain of both sexes of rats undergoing Ischemia-reperfusion (I/R). To induce I/R injury in rats, 4-vessels occlusion model was used. Gemfibrozil was administered to animals through gavage. Data collection was performed using western blotting, as well as histological and antioxidant enzyme assays. Pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. While the expression of NRF-1 and TFAM were induced in gemfibrozil-pretreated met-estrous females, they were suppressed in males. Gemfibrozil also proved to be neuroprotective in met-estrous females, as it inhibited caspase-dependent apoptosis while in males it led to hippocampal neurodegeneration via activation of both the caspase-dependent and caspase-independent apoptosis. In the mitogen-activated protein kinase (MAPKs) pathway, gemfibrozil pretreatment induced the expression of extracellular signal-regulated kinases (ERK1/2) in met-estrous females and reduced it in males. These findings correlatively point to the sexual-dimorphic effects of gemfibrozil in global cerebral I/R context, especially through modulation of the mitochondrial biogenesis pathway, as well as MAPKs and apoptotic cell death pathways.

Biography :

Leila Khalaj has completed her PharmD and her PhD from Shahid Beheshti University of Medical Sciences. She has done her Post-doctoral studies in Neuroscience Research Center of Shahid Beheshti University and her sabbatical leave in Eskitis Institute for Cell and Molecular Therapies, Brisbane, Australia. She has published more than 14 papers in reputed journals, and currently she is an Assistant Professor in Alborz University of Medical Sciences, Alborz, Iran.