Hang Wu1, Zhi-Gang Wu2, Wen-Jing Shi3, Hui Gao4, Hong-Hai Wu5, Fang Bian6, Peng-Peng Jia6, Yan-Ning Hou7. 1. Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China. Electronic address: wuhang19870505@163.com. 2. Department of Pharmacy, Hebei North University, Hebei Key Laboratory of Neuropharmacology, Zhangjiakou, 075000, China. Electronic address: wuzhigang1982@126.com. 3. Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China; Department of Pharmacy, Hebei General Hospital, Shijiazhuang, 050051, Hebei Province, China. Electronic address: kathy2587@163.com. 4. Department of Clinical Medicine, Heze Medical College, Heze, 274000, Shandong Province, China. Electronic address: tsyxygaohui@163.com. 5. Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang, 050082, Hebei Province, China. Electronic address: wuhonghai@sohu.com. 6. Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China. 7. Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China; Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang, 050082, Hebei Province, China. Electronic address: biph2011@163.com.
Abstract
AIMS: Alzheimer's disease (AD) is closely related to abnormal glucose metabolism in the central nervous system. Progesterone has been shown to have obvious neuroprotective effects in the pathogenesis of AD, but the specific mechanism has not been fully elucidated. Therefore, the purpose of this study was to investigate the effect of progesterone on the glucose metabolism of neurons in amyloid precursor protein (APP)/presenilin 1 (PS1) mice and Aβ-induced AD cell model. MATERIALS AND METHODS: APP/PS1 mice were treated with 40 mg/kg progesterone for 40 days and primary cultured cortical neurons were treated with 1 μM progesterone for 48 h.Then behavior tests,2-NBDG glucose uptake tests and the protein levels of glucose transporter 3 (GLUT3), GLUT4, cAMP-response element binding protein (CREB) and proliferator-activated receptor γ (PPARγ) were examined. KEY FINDINGS: Progesterone increased the expression levels of GLUT3 and GLUT4 in the cortex of APP/PS1 mice, accompanied by an improvement in learning and memory. Progesterone increased the levels of CREB and PPARγ in the cerebral cortex of APP/PS1 mice. In vitro, progesterone increased glucose uptake in primary cultured cortical neurons, this effect was blocked by the progesterone receptor membrane component 1 (PGRMC1)-specific blocker AG205 but not by the progesterone receptor (PR)-specific blocker RU486. Meanwhile, progesterone increased the expression of GLUT3, GLUT4, CREB and PPARγ, and AG205 blocked this effect. SIGNIFICANCE: These results confirm that progesterone significantly improves the glucose metabolism of neurons.One of the mechanisms of this effect is that progesterone upregulates protein expression of GLUT3 and GLUT4 through pathways PGRMC1/CREB/GLUT3 and PGRMC1/PPARγ/GLUT4.
AIMS: Alzheimer's disease (AD) is closely related to abnormal glucose metabolism in the central nervous system. Progesterone has been shown to have obvious neuroprotective effects in the pathogenesis of AD, but the specific mechanism has not been fully elucidated. Therefore, the purpose of this study was to investigate the effect of progesterone on the glucose metabolism of neurons in amyloid precursor protein (APP)/presenilin 1 (PS1) mice and Aβ-induced AD cell model. MATERIALS AND METHODS:APP/PS1mice were treated with 40 mg/kg progesterone for 40 days and primary cultured cortical neurons were treated with 1 μM progesterone for 48 h.Then behavior tests,2-NBDG glucose uptake tests and the protein levels of glucose transporter 3 (GLUT3), GLUT4, cAMP-response element binding protein (CREB) and proliferator-activated receptor γ (PPARγ) were examined. KEY FINDINGS:Progesterone increased the expression levels of GLUT3 and GLUT4 in the cortex of APP/PS1mice, accompanied by an improvement in learning and memory. Progesterone increased the levels of CREB and PPARγ in the cerebral cortex of APP/PS1mice. In vitro, progesterone increased glucose uptake in primary cultured cortical neurons, this effect was blocked by the progesterone receptor membrane component 1 (PGRMC1)-specific blocker AG205 but not by the progesterone receptor (PR)-specific blocker RU486. Meanwhile, progesterone increased the expression of GLUT3, GLUT4, CREB and PPARγ, and AG205 blocked this effect. SIGNIFICANCE: These results confirm that progesterone significantly improves the glucose metabolism of neurons.One of the mechanisms of this effect is that progesterone upregulates protein expression of GLUT3 and GLUT4 through pathways PGRMC1/CREB/GLUT3 and PGRMC1/PPARγ/GLUT4.
Authors: Baruh Polis; Margherita Squillario; Vyacheslav Gurevich; Kolluru D Srikanth; Michael Assa; Abraham O Samson Journal: Neurochem Res Date: 2022-01-31 Impact factor: 3.996