NeuroSci
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2025
·Vol. 6
·期 2
·28
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IF 2
Fengzhi Sun,Lijie Xia,Baokun Wang,Yanao Liu,Xiaotong Cui,Huijun Kang,Rostyslav Stoika,Kechun Liu,Meng Jin
Reserpine is used as a cheap and effective first-line antihypertensive, and presently, it is applied as treatment for difficult-to-control cases of hypertension. Despite its significance, reserpine’s neuroendocrine toxicity remains largely underexplored. Here, we investigated the effects of reserpine on development, locomotion, central nervous system (CNS) neurons, thyroid development, and the expression of genes related to neurodevelopment, endocrine, learning and memory, and depression in zebrafish exposed to different doses of reserpine ranging from 0.5 mg/L to 16 mg/L. The results of our study demonstrated that reserpine exerts dose-dependent toxicity on the neuroendocrine system (NES). An investigation into its underlying mechanism suggests that reserpine disrupted the hypothalamic–pituitary–thyroid (HPT) axis via down-regulatinghhex,tg, andtshβgenes, impairing thyroid hormone synthesis and endocrine balance. Meanwhile, it affected neurodevelopment, as evidenced by the reduced expression ofgfap,gap43,mbp,syn2a, andtuba1bgenes, which compromised neuronal structure and function, while impaired neurotransmitter release and uptake could occur due to the suppression ofcrhbandmaogenes. To conclude, these findings illustrate the interconnected impact of pathways involved in endocrine and neurodevelopment in reserpine-induced toxicity.
研究领域:
毒理学
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神经生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2023
·Vol. 103
·期 12
·5839-5848
·
IF 4.1
Xuan Yao,Anqi Wang,Bo Gao,Yu Xue,Xueling Zhao,Xuanyu Wang,Rui Wang,Min Zhuang,Changqing Wei,Weidong Cheng,Jian Zhang,Padraig Strappe,Zhongkai Zhou
BACKGROUND Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d -galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch–oleic acid showed a greater improvement compared to others. In addition, de-branched starch–capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch–capric acid and –oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia . Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch–capric acid complex diet. In summary, de-branched starch–capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.
研究领域:
营养学
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老年医学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jun Liu,Tao Gao,Bin Zhou,Xiaoxiao Xu,Xiaojie Zhai,Qinghuan Yao,Xiaowei Chen,Lin Liu,Wei Cui,Xiang Wu
Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10–12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor-κB (NF-κB), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD.
研究领域:
神经科学
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药理学
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外科手术
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Sheng-Quan Su,Gui-Yuan Xiong,Chun-Yan Yao,Xiao-Ling Liu,Yin-Yin Xia,Jin-Yun Long,Xiu-Kuan Li,Liang-Mei Wang,Long Yi,Wu-Wei Xu,Wu-Qiang Lu,Qian-Qian Li,Ting Hu,Hao Liu,Ke-Xue Wang,Peng Luo,Tong-Jian Cai
T-2 toxin, classified as a mycotoxin, harms immune and cognitive systems. Recently, an increasing number of studies have focused on the neurotoxic effects of T-2 toxin. However, there is still a need for a better understanding of the molecular mechanisms involved. In this study, we aimed to elucidate the protective effect of resveratrol (Res) supplementation against T-2 toxin-induced spatial learning and memory impairment and to investigate the communication mechanisms between the gut and the brain. Mice received a single intraperitoneal dose of T-2 toxin (4 mg/kg) followed by Res (100 mg/kg) administered via the same route. The Morris water maze and novel object recognition tests demonstrated that T-2 toxin had a profound negative impact on spatial learning and memory in mice. However, the administration of Res successfully mitigated the cognitive impairments caused by T-2 toxin and notably enhanced the levels of brain-derived neurotrophic factor (BDNF), synaptophysin I (SYN1), and postsynaptic density protein 95 (PSD-95). Moreover, Res demonstrated a protective effect against T-2 toxin-induced damage to hippocampal tissue. Simultaneously, it played a pivotal role in restoring gut microbiota equilibrium and maintaining the integrity of intestinal tight junctions, effectively curbing both localized and systemic inflammation triggered by T-2 toxin exposure. In conclusion, our findings suggest that resveratrol may alleviate T-2 toxin-induced spatial learning and memory deficits, possibly via gut-brain axis modulation.
研究领域:
神经毒理学
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神经科学
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毒理学
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药理学
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微生物学
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免疫学
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认知科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Jia Lv,Yanling Li,Jianrong Chen,Rong Li,Chao Bao,Zheng Ding,Wenqiang Ren,Zhiping Du,Sheng Wang,Yichao Huang,Qu-nan Wang
Prenatal DEHP exposure can cause offspring neurodevelopmental toxicity, but the persistent effects of such exposure window are unclear. This study aimed to investigate the lasting neurobehavioral impact of DEHP on offspring following early exposure from GD9.5 (fetal neural tube closure) to GD16.5 (fetal thyroxin , TH, synthesis). Data showed maternal exposure to DEHP during the thyroid hormone-dependent stage induced a range of neurobehavioral phenotypic changes in adult and middle-aged mice, including anxiety, depression and cognitive impairment . Significant reductions in free TH, TH transporters, and TH metabolic enzyme deiodinase II (D2) were observed in the fetal brain, whereas D3 was elevated, indicating that TH signaling disruption was caused by in utero exposure. Gene expression analyses suggested the expression levels of the TH receptors Trα1 , Trβ1 and their downstream target, brain-derived neurotrophic factor, were significantly attenuated, which may partially explain the mechanisms of neurodevelopmental impairment. This study provides new evidence of the persistent effects of sex-specific neurodevelopmental impairment due to in utero DEHP exposure, possibly through damage to the fetal brain TH signaling systems that causes lifelong brain damage. These results further suggest a profound neurobehavioral toxicity of DEHP that may be programmed during early developmental stage exposure and manifested later in life.
研究领域:
神经科学
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毒理学
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发育生物学
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内分泌学
✓ 已验证
DOI
PubMed
高影响因子
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