期刊
FRONTIERS IN PHYSIOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2022.983506
关键词
ASIC; pregnancy; synaptosomes; eclampsia; microglia; cytokines; GABA; glutamate
类别
资金
- COBRE pilot
- National Institutes of Health
- K99/R00 award [P20GM104357]
- National Institute of General Medical Sciences of the NIH [R00HL129192, R00HL129192-S1]
- William Townsend Porter Fellowship [P30GM103328]
- [T32HL105324]
This study found that pregnant mice with reduced ASIC2a expression may not be able to mount an inflammatory response following acute seizure exposure. Due to the decrease in ASIC2a, the concentration of pro-inflammatory cytokines and chemokines in the hippocampal cytosolic fraction of pregnant mice was reduced.
Acid sensing ion channels (ASICs) are mechano- and chemo-receptor channels that are activated by drops in extracellular pH as occurs after neurotransmission. In our previous study, we demonstrated that mice subjected to reduced uteroplacental perfusion pressure during pregnancy, to mimic the pregnancy complication of preeclampsia, have reduced hippocampal expression of ASIC2a protein. We also showed that pregnant mice with heterozygous expression of ASIC2a (+/-) had increased sensitivity and severity to pentylenetetrazol-induced seizures; however, the mechanisms by which this occurs remain unclear. The purpose of this study was to investigate key molecular targets involving neurotransmission and inflammation that are differentially changed following seizure exposure in pregnant ASIC2a +/- mice. On gestational day 18.5, ASIC2a wild-type (+/+, n = 7) and +/- (n = 14) mice were injected with 40 mg/kg pentylenetetrazol and monitored for 30 min. Western blot and ELISA analysis revealed no difference in hippocampal synaptosome glutamate-related proteins but an increase in GABA concentration in pregnant +/- mice. Using ELISA and multiplex assays, we found a significant decrease in serum TNF alpha, and a decreased concentration of pro-inflammatory cytokines and chemokines in hippocampal cytosolic fraction. Significant reductions in IL-1 beta, IL-3, IL-12 (p70), eotaxin, interferon gamma, and macrophage inflammatory protein (MIP-1 beta), in the hippocampal cytosolic fractions of +/- mice were observed compared to +/+ mice. Additionally, there was no difference in hippocampal microglia density or activation in pregnant ASIC2a+/+ vs. +/- mice. These results support the hypothesis that pregnant mice with reduced ASIC2a may not be able to mount an inflammatory response following acute seizure exposure.
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