Progesterone modulates striatal lipid profile in rat cerebral hypoperfusion model

Abstract

Prolonged disturbance of cerebral blood flow causes metabolic insufficiency and neuronal hypofunction, for which there is still no adequate therapeutic strategy. In several animal models of neurodegenerative diseases, progesterone (P4), a potent gonadal steroid hormone, and its metabolites showed neuroprotective outcomes through reduction of oxidative stress and stabilization of membrane lipids and their downstream signalling. As P4 actions in rat striatum following permanent bilateral occlusion of both common carotid arteries are still uncertain, we investigated its capacity to reduce neuronal damage induced by permanent occlusion of both carotid arteries (2VO), focusing on several oxidative stress markers (end products of lipid peroxidation (LPP) and phosphatidylcholine (PC) to lysophosphatidylcholine (LPC) intensity ratio) in crude synaptosomal fraction. Adult male Wistar rats were divided into groups: control ‒ sham operated animals treated with vehicle (commercial flax oil, 1 mg/kg) and permanently occluded animals subjected to either vehicle (commercial flax oil, 1 mg/kg) or P4 (dissolved in commercial flax oil, 1.7 mg/kg). Animals were subcutaneously injected for 7 days and sacrificed 4 h following the last treatment. LPP levels were determined spectrophotometrically, while PC/LPC intensity ratio was estimated by mass spectrometer. Obtained results indicate that P4 treatment alleviates 2VO – induced prooxidative changes by decreasing LPP levels and elevating PC/LPC intensity ratio, and returning them closer to levels observed in controls. According to our findings, P4 treatment in cerebral hypoperfusion model, via targeting striatal cell lipid components and altering lipid profile, might be implicated in reduction of oxidative stress and promotion of protective environment.