Nicotine Alleviates Cortical Neuronal Injury by Suppressing Neuroinflammation and Upregulating Neuronal PI3K-AKT Signali

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ORIGINAL ARTICLE

Nicotine Alleviates Cortical Neuronal Injury by Suppressing Neuroinflammation and Upregulating Neuronal PI3K-AKT Signaling in an Eclampsia-Like Seizure Model Xinjia Han 1 & Ning Zhou 2 & Huiping Hu 1 & Xin Li 3 & Huishu Liu 1 Received: 6 March 2020 / Revised: 27 July 2020 / Accepted: 28 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Our previous studies showed that treatment with alpha7 nicotinic acetylcholine receptor (α7nAChR) agonist nicotine could alleviate systemic inflammation and reduce neuronal loss in the hippocampus and seizure severity in eclampsia. In this study, we further investigated whether there is also neuronal damage in the cortex after eclamptic seizure, elucidated the potential mechanisms underlying the neuroprotective roles of nicotine in eclampsia. Retrospective analysis of MRI data of severe preeclampsia (SPE) patients was conducted. A preeclampsia model was established by lipopolysaccharide injection (PE group), and pentylenetetrazol was used to induce eclamptic seizure (E group). α7nAChR agonist nicotine and its antagonist (α-BGT) and PI3K inhibitor wortmannin were used for drug administration. Neuronal damage was detected by Nissl staining, and changes in neuroinflammation, neuronal apoptosis, α7nAChR expression, and PI3K-AKT signaling on cortical neurons were detected by immunohistochemistry and western blotting. MRI images showed that most abnormal signals from the brain of SPE patients were located in the cortex. The neuron survival ratio was lower in the cortex than in the hippocampus within the E group; such ratios in the cortex were significantly lower in the E and PE groups compared with those of the control group. Nicotine markedly decreased the production of inflammatory cytokines and microglial activation in the cortex of the E group. Moreover, nicotine increased p-AKT levels and decreased cleaved caspase-3 levels in cortical neurons. Treatment with α-BGT reversed effects of nicotine. Wortmannin also blocked the anti-neuronal apoptosis action of nicotine. Our results suggest that nicotine protects against neuronal injury in the cortex following eclampsia possibly by inhibiting neuroinflammation and activating neuronal PI3K-AKT pathway. Keywords alpha7 nicotinic acetylcholine receptor . Nicotine . Cortex . Neuronal loss . Neuroinflammation . Cleaved caspase-3

Introduction Preeclampsia and eclampsia are serious forms of gestational hypertension. If not properly managed, preeclampsia progresses to eclampsia. The major clinical symptoms of preeclampsia are high blood pressure and proteinuria, and

* Huishu Liu [email protected] 1

Department of Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, China

2

Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China

3

Department of Obstetrics and Gynaecology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei, China

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