Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor.
A considerable number of studies have demonstrated that nicotine, a α7-nicotinic acetylcholine receptor (α7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α7-nAChRs have been investigated after inducing eclampsia-like seizures in rats.



Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14-19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining.



Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-α, IL-1β, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), and dramatically increased eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α-bungarotoxin, a selective α7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats.



Our findings indicate that the administration of nicotine may attenuate microglial activity and increase eclampsia-like seizure threshold in rat hippocampus through the α7 nicotinic receptor.
Guangzhou Medical University, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Xiaolan
X
Li
Guangzhou Medical University, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Xinjia
X
Han
Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Junjie
J
Bao
Guangzhou Medical University, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Yuanyuan
Y
Liu
Guangzhou Medical University, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China.
Aihua
A
Ye
Amity Institute of Wildlife Sciences, Amity University, Noida 201313, Uttar Pradesh, India.
Mukesh
M
Thakur
Guangzhou Medical University, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, China. Electronic address: huishuliu@hotmail.com.
Huishu
H
Liu
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004461:Eclampsia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010433:Pentylenetetrazole; D011247:Pregnancy; D011256:Pregnancy Outcome; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D010433:Pentylenetetrazole
Eclampsia; Hippocampal neuron; Inflammatory cytokines; Microglia; Nicotine