Jing Guan1, Beibei Yang, Yi Fan, Ji Zhang. 1. State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Abstract
OBJECTIVE: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. METHODS: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. RESULTS: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. CONCLUSION: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.
OBJECTIVE: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. METHODS: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. RESULTS: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. CONCLUSION: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.
Authors: Natalie C Fredette; Eliyah Malik; Marah L Mukhtar; Eric R Prossnitz; Naohiro Terada Journal: Am J Physiol Cell Physiol Date: 2020-08-12 Impact factor: 4.249
Authors: Elisabeth G Hain; Maria Sparenberg; Justyna Rasińska; Charlotte Klein; Levent Akyüz; Barbara Steiner Journal: J Neuroinflammation Date: 2018-05-26 Impact factor: 8.322