Effects of estrogen receptor GPR30 agonist G1 on neuronal apoptosis and microglia polarization in traumatic brain injury rats

Abstract

PurposeTo investigate the effects of estrogen G protein-coupled receptor 30 (GPR30) agonist G1 on hippocampal neuronal apoptosis and microglial polarization in rat traumatic brain injury (TBI).MethodsMale SD rats were randomly divided into sham group, TBI + vehicle group, TBI + G1 group. Experimental moderate TBI was induced using Feeney's weigh-drop method. G1 (100μg/kg) or vehicle was intravenously injected from femoral vein at 30 min post-injury. Rats were sacrificed at 24 h after injury for detection of neuronal apoptosis and microglia polarization. Neuronal apoptosis was assayed by immunofluorescent staining of active caspase-3. M1 type microglia markers (iNOS and IL-1β) and M2 type markers (Arg1 and IL-4) were examined by immunoblotting or ELISA. Total protein level of Akt and phosphorylated Akt were assayed by immunoblotting.ResultsG1 significantly reduced active caspase-3 positive neurons in hippocampus. Meanwhile G1 increased the ratio of Arg1/iNOS. IL-1β production was decreased but IL-4 was increased after G1 treatment. G1 treatment also increased the active form of Akt.ConclusionsGPR30 agonist G1 inhibited neuronal apoptosis and favored microglia polarization to M2 type.

Estrogen promotes pro-resolving microglial behaviour and phagocytic cell clearance through the actions of annexin A1

“…Interestingly, this dichotomy of effect was not replicated in the effects of estrogen receptor activation upon microglial phenotype, with both ERβ and GPER selective ligands being equipotent in ameliorating LPS-induced pro-inflammatory signs. This finding accords well with published studies that show exogenous administration of the GPER agonist G1 to prevent inflammatory microglial activation in vivo [36][37][38] , and that identify a mediatory role for GPER in the anti-inflammatory effects of estrogen in cerebral ischaemia 39 . These anti-inflammatory effects of estrogen or its receptor-specific mimetics again appeared to be mediated in large part through AnxA1, with microglia stably bearing AnxA1-targeting shRNA sequences showing a clear impairment in many of the anti-inflammatory actions of estrogen and its mimetics.…”

Neuroprotective Effect of Low-Intensity Transcranial Ultrasound Stimulation in Moderate Traumatic Brain Injury Rats

“…Therefore, these two models were not selected in this study. Moderate TBI model rats often have difficulties in recovery and exhibit an appropriate degree of neurological damage, which is suitable for evaluating the treatment of LITUS (Pan et al, 2019).…”

“…The impact device had several parameters: the impact hammer weight was 21 g, the impact pipe length was 26 cm, the impact bar diameter was 4.6 mm, and the end extended 4 mm beyond the lower edge of the catheter. Freefall blows using these parameters results in moderate traumatic brain injury (Pan et al, 2019). Humane care was given to the rats according to the 3R principles of experimental animals, and the rats were weighed according to the aseptic operation procedures.…”

Microglia: A Potential Drug Target for Traumatic Axonal Injury

“…For example, in a CCI model of TBI, postovariectomy female mice with severe cerebral injuries at multiple brain sites showed enhanced microglial activation compared to intact females, as indicated by Iba-1 [107]. In post-TBI rats, the G1 agonist of estrogen receptor GPR30 was found to improve M2 polarization, as indicated by Arg1 and IL-4, leading to induced neural protection [115].…”