Participation of the HIF-1alpha/VEGF signaling in the GPER-1-induced neuroprotection in a cortical brain in vitro model of oxygen/glucose deprivation

Abstract

Much has been known in recent decades about the effects of estrogen on the body, in addition to its classic effects on reproduction. Its role on the central nervous system (CNS) proved to be extremely important, especially in pathological conditions where neuroprotective effects have been demonstrated. Intracellularly, estrogen interacts not only with its classical nuclear receptors (ERa and ERb), leading to modulation of transcription, but also with GPER-1 (G-coupled Estrogen Receptor), via fast intracellular signaling. Both ERs and GPER-1 can mediate estrogenic protective actions in the CNS by modulating neurotoxicity inhibition and promoting neuronal survival and revascularization. In studies on breast cancer cells and myocardial ischemic injuries, the relationship between the activation of GPER-1 and the HIF-1alpha/VEGF signaling pathway, responsible for tissue revascularization, was observed. In cerebral ischemia, when the cerebral blood flow is compromised, revascularization is fundamental for the reestablishment of its proper functioning. The mechanisms of this process, however, have not yet been fully elucidated. Using primary cell cultures from the barin cortex of newborn rats, our study aims to elucidate the participation of the HIF1alpha/VEGF pathway in the GPER-1 mediated estrogen induced-neuroprotection related to revascularization in ischemic processes. We feel that if we evidence such rapid signaling as a source of neuroprotection in cases of ischemia, new therapeutic targets and, therefore, new pharmacological tools will emerge, making possible not only the success of the treatment, but also a better prognosis of people affected by this situation.