λ-cyhalothrin induced sex-specific inflammation, glia activation and GABAergic interneuron disruption in the hippocampus of rats.

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Aminu Imam, Christianah Oyegbola, Maryam Busari, Adewumi Mercy Gbemisola, Laaro Abubakar, Ajala Taofeeqoh Odunayo, Alhassan Godwin Attai, Ajibola Musa Iyiola, Wahab Abdulmajeed Imam, Aalimah Akinosho Akorede, Omamuyovwi Meashack Ijomone, Moyosore Salihu Ajao
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Abstract

Background: Glia mediated neuroinflammation and degeneration of inhibitory GABAergic interneurons are some of the hall marks of pyrethroid neurotoxicity. Here we investigated the sex specific responses of inflammatory cytokines, microglia, astrocyte and parvalbumin positive inhibitory GABAergic interneurons to λ-cyhalothrin (LCT) exposures in rats.

Methods: Equal numbers of male and female rats were given oral corn oil, 2 mg/kg.bw and 4 mg/kg.bw of LCT for fourteen days. They were euthanized on day 15, brains were excised and hippocampus (n = 5/group) isolated for interleukin 1 beta (IL-1β) and tumor necrotic factor alpha (TNF-α) analysis. The remaining brains (n = 3/group) were processed for Ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP) and parvalbumin (PV) distribution in the hippocampus. All quantitative data was subjected to one way analysis of variance (ANOVA).

Results: LCT caused sex and dose dependent increase in IL-1β and TNF-α concentrations, distribution of microglia (Iba1+) and astrocytes (GFAP+), and reduction of PV + GABAergic interneurons. These effects were greater in males compared to females, and dose-dependent in both sexes.

Conclusion: LCT specifically induced inflammation and disrupted GABAergic interneurons' integrities via activation of microglia and reactive astrogliosis and such effects are dose-dependent and sexually dimorphic.

λ-氯氟氰菊酯诱导大鼠海马性别特异性炎症、胶质细胞激活和gaba能间神经元破坏。
背景:神经胶质介导的神经炎症和抑制性gaba能中间神经元的变性是拟除虫菊酯神经毒性的一些标志。本研究研究了大鼠炎症细胞因子、小胶质细胞、星形胶质细胞和小白蛋白阳性抑制性gaba能中间神经元对λ-氯氟氰菊酯(LCT)暴露的性别特异性反应。方法:给等量雌雄大鼠口服玉米油2 mg/kg。体重和4毫克/公斤。14天的LCT。第15天安乐死,切除脑组织,分离海马(n = 5/组)进行白细胞介素1β (IL-1β)和肿瘤坏死因子α (TNF-α)分析。其余脑(n = 3/组)处理电离钙结合接头分子1 (Iba1)、胶质纤维酸性蛋白(GFAP)和海马小白蛋白(PV)分布。所有定量数据均采用单因素方差分析(ANOVA)。结果:LCT引起IL-1β和TNF-α浓度的性别和剂量依赖性增加,小胶质细胞(Iba1+)和星形胶质细胞(GFAP+)的分布,PV + gaba能中间神经元的减少。与女性相比,这些影响在男性中更大,并且在两性中都是剂量依赖性的。结论:LCT通过激活小胶质细胞和反应性星形胶质形成特异性地诱导炎症和破坏gaba能中间神经元的完整性,这种影响是剂量依赖性的和性别二态性的。
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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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