Acid Sensing Ion Channel 2a Is Reduced in the Reduced Uterine Perfusion Pressure Mouse Model and Increases Seizure Susceptibility in Pregnant Mice
Autor: | James P. Shaffery, Maria Jones-Muhammad, Junie P. Warrington, Loretta R. Cain-Shields, Qingmei Shao |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty QH301-705.5 Placenta seizure Respiratory arrest Hippocampal formation Hippocampus Article Preeclampsia eclampsia Mice 03 medical and health sciences 0302 clinical medicine Seizures Internal medicine medicine Animals Pentylenetetrazol Biology (General) Acid-sensing ion channel Mice Knockout Pregnancy Eclampsia business.industry General Medicine pentylenetetrazol medicine.disease Acid Sensing Ion Channels Mice Inbred C57BL 030104 developmental biology Endocrinology ASIC2a RUPP placental ischemia Gestation Female pregnancy medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Cells Volume 10 Issue 5 Cells, Vol 10, Iss 1135, p 1135 (2021) |
ISSN: | 2073-4409 |
DOI: | 10.3390/cells10051135 |
Popis: | Eclampsia is diagnosed in pregnant women who develop novel seizures. Our laboratory showed that the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia displays reduced latency to drug-induced seizures. While acid sensing ion channels (ASIC1a and 3) are important for reducing seizure longevity and severity, the role of ASIC2a in mediating seizure sensitivity in pregnancy has not been investigated. We hypothesized that 1) RUPP reduces hippocampal ASIC2a, and 2) pregnant mice with reduced ASIC2a (ASIC2a+/−) have increased seizure sensitivity. On gestational day 18.5, hippocampi from sham and RUPP C57BL/6 mice were harvested, and ASIC2a was assessed using Western blot. Pregnant wild-type and ASIC2a+/− mice received 40 mg/kg of pentylenetetrazol (i.p.) and were video recorded for 30 min. Behaviors were scored using a modified Racine scale (0–7: 0 = no seizure 7 = respiratory arrest/death). Seizure severity was classified as mild (score = 1–3) or severe (score = 4–7). RUPP mice had reduced hippocampal and placental ASIC2a protein. ASIC2a+/− mice had reduced latency to seizures, increased seizure duration, increased severe seizure duration, and higher maximum seizure scores. Reduced hippocampal ASIC2a in RUPP mice and increased seizure activity in pregnant ASIC2a+/− mice support the hypothesis that reduced ASIC2a increases seizure sensitivity associated with the RUPP. |
Databáze: | OpenAIRE |
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