Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor

Abstract Objective 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 c...

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Published in:Brain research 2016-07, Vol.1642, p.487-496
Main Authors: Li, Xiaolan, Han, Xinjia, Bao, Junjie, Liu, Yuanyuan, Ye, Aihua, Thakur, Mukesh, Liu, Huishu
Format: Article
Language:English
Subjects:
alpha7 Nicotinic Acetylcholine Receptor - agonists
alpha7 Nicotinic Acetylcholine Receptor - antagonists & inhibitors
alpha7 Nicotinic Acetylcholine Receptor - metabolism
Animals
Astrocytes - drug effects
Astrocytes - pathology
Astrocytes - physiology
Blood Pressure - drug effects
Blood Pressure - physiology
CA1 Region, Hippocampal - drug effects
CA1 Region, Hippocampal - pathology
CA1 Region, Hippocampal - physiopathology
Cytokines - metabolism
Disease Models, Animal
Drug Evaluation, Preclinical
Eclampsia
Eclampsia - drug therapy
Eclampsia - pathology
Eclampsia - physiopathology
Female
Hippocampal neuron
Inflammatory cytokines
Lipopolysaccharides
Microglia
Microglia - drug effects
Microglia - pathology
Microglia - physiology
Neuroimmunomodulation - drug effects
Neuroimmunomodulation - physiology
Neurology
Neurons - drug effects
Neurons - pathology
Neurons - physiology
Nicotine
Nicotine - pharmacology
Nicotinic Agonists - pharmacology
Pentylenetetrazole
Pregnancy
Pregnancy Outcome
Random Allocation
Rats, Sprague-Dawley
Seizures - drug therapy
Seizures - pathology
Seizures - physiopathology
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Summary:Abstract Objective 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. Methods 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 to 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. Results 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. Conclusion 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.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2016.04.043