Neurotoxicology最新文献

Abnormal lipid metabolism and inflammatory response induced by aluminum led to the cognitive decline in mice 铝引起的脂质代谢异常和炎症反应导致小鼠认知能力下降

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.012

Rong Feng , Zhongyao Chen , Liang Chen , Wei Wei , Jiafeng Wen , Jingyu Zheng

{"title":"Abnormal lipid metabolism and inflammatory response induced by aluminum led to the cognitive decline in mice","authors":"Rong Feng , Zhongyao Chen , Liang Chen , Wei Wei , Jiafeng Wen , Jingyu Zheng","doi":"10.1016/j.neuro.2025.04.012","DOIUrl":"10.1016/j.neuro.2025.04.012","url":null,"abstract":"<div><div>As a chronic, low-toxicity metal, the effect of aluminum on human body has been paid more and more attention; however, the exact mechanism of action remains unclear. In this study, we studied the effects of aluminum on oxidative stress, inflammation, and mild cognitive impairment in mice, and analyzed changes in fecal metabolites to elucidate the potential mechanisms underlying these interactions. After 120 days of aluminum feeding, behavioral tests revealed that mice in the high-dose aluminum group exhibited cognitive decline. Regarding oxidative stress indices, MDA level increased, while GSH-PX activity, GSH content and CAT activity decreased significantly in aluminum treatment group. MAO activity increased and TC content decreased significantly. Pathological analysis of tissue sections showed that there was inflammation in brain tissue of high dose group. Pro-inflammatory factors TNF-α and IL-1β in brain tissue were significantly increased. Four metabolites (arachidic acid, linoleic acid squalene and <em>P</em>-cymene) involved in lipid metabolic pathways and inflammation varied significantly in the feces of each group. Therefore, aluminum-induced abnormal lipid metabolism pathway and inflammatory response may be an important cause of the cognitive decline.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 281-294"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity by reducing Aβ accumulation, oxidative stress and inflammatory reaction 甘草查尔酮A通过减少Aβ积累、氧化应激和炎症反应对氯化铝诱导的神经毒性的神经保护作用

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.011

Zhijuan Tang , Fang Wang , Jintao Lv , Gaohong Yang , Xinchun Shen , Fei Zeng , Lingling Meng , Wen Zhou , Libin Zhan , Zebin Weng

{"title":"Neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity by reducing Aβ accumulation, oxidative stress and inflammatory reaction","authors":"Zhijuan Tang , Fang Wang , Jintao Lv , Gaohong Yang , Xinchun Shen , Fei Zeng , Lingling Meng , Wen Zhou , Libin Zhan , Zebin Weng","doi":"10.1016/j.neuro.2025.04.011","DOIUrl":"10.1016/j.neuro.2025.04.011","url":null,"abstract":"<div><div>Excessive aluminum exposure is a contributing factor in several neurodegenerative diseases. Natural plant compounds such as Licochalcone A have been shown to have significant neuroprotective effects <em>in vivo</em> and <em>in vitro</em>. In this study, we aim to elucidate the neuroprotective effect of Licochalcone A against aluminum chloride-induced neurotoxicity and its possible mechanism. Adult zebrafish and PC12 cells were used as animal and cell models. Zebrafish and PC12 cells were treated with excessive aluminum trichloride (100 μg/L aluminum chloride hexahydrate solutions for zebrafish or 500 μM Al-malt solution for PC12 cells) to cause neuronal damage. The neuroprotective effect of Licochalcone A was evaluated by measuring ROS production, Aβ<sub>1–42</sub> accumulation, inflammatory cytokines, neuronal apoptosis-associated genes, and MAPK pathway-related proteins to elucidate the mechanism of Licochalcone A against aluminum chloride-induced neurotoxicity. Licochalcone A effectively reduced the level of ROS production and inflammatory cytokines in both zebrafish and PC12 cells treated with excessive aluminum trichloride. In addition, Licochalcone A reduced the expression of BACE1 and generation of Aβ<sub>1–42</sub> as well as the expression of p-JNK and MAPK, the key factor of the MAPK pathway. These results indicated that Licochalcone A has a remarkable neuroprotective effect against neurotoxicity induced by aluminum and has a high potential in the development of therapeutic drugs for neurodegenerative diseases.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 295-305"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

2,4,6-trinitrotoluene induces neurotoxicity by affecting the G protein pathways in Caenorhabditis elegans 2,4,6-三硝基甲苯通过影响秀丽隐杆线虫的G蛋白通路诱导神经毒性

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.014

Ying Li , Yanping Zhou , Chunyan Wang , Yaguang Nie , Yongbing Zhu , Sanping Zhao , Lijun Wu , An Xu

{"title":"2,4,6-trinitrotoluene induces neurotoxicity by affecting the G protein pathways in Caenorhabditis elegans","authors":"Ying Li , Yanping Zhou , Chunyan Wang , Yaguang Nie , Yongbing Zhu , Sanping Zhao , Lijun Wu , An Xu","doi":"10.1016/j.neuro.2025.04.014","DOIUrl":"10.1016/j.neuro.2025.04.014","url":null,"abstract":"<div><div>2,4,6-trinitrotoluene (TNT) is a chemical widely used to make explosives, and its use of residues can lead to potential threats to both ecosystems and human health. A thorough understanding of the various toxic effects of TNT is essential for developing effective environmental protection and health safety measures. Thus, we employed <em>Caenorhabditis elegans</em> (<em>C. elegans</em>), a typical model organism, to explore the neurotoxic effects of TNT and the signaling pathways involved. The results showed that neurotoxicity induced by 10–100 ng/mL TNT was manifested in reduced behavioral capacity (head thrashes, body bends, and pharyngeal pumping rates), and inhibition of foraging behavior and ethanol avoidance behavior. Using fluorescence-labeled transgenic nematodes, it was found that TNT damaged dopaminergic and cholinergic neurons, which resulted in a significant decrease in the release of neurotransmitters and the expression of associated genes (<em>dat-1</em> and <em>unc-17</em>). We studied the role of G protein signaling pathways and discovered that the related genes (<em>egl-30</em>, <em>gsa-1</em>, <em>goa-1</em>, and <em>unc-13</em>) were significantly down-regulated, resulting in reduced acetylcholine release, which in turn corresponded to the observed behavioral abnormality and damaged neurons in the worms. This study shed light on TNT’s neurotoxic mechanisms and associated health risks.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 328-337"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developmental neurotoxicity of bisphenol F and bisphenol S in animal model systems: A literature review 双酚F和双酚S在动物模型系统中的发育性神经毒性：文献综述

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.008

Ricardo Cantua, Kimberly Mulligan

{"title":"Developmental neurotoxicity of bisphenol F and bisphenol S in animal model systems: A literature review","authors":"Ricardo Cantua, Kimberly Mulligan","doi":"10.1016/j.neuro.2025.04.008","DOIUrl":"10.1016/j.neuro.2025.04.008","url":null,"abstract":"<div><div>Neurodevelopmental disorders have complex etiologies, stemming both from genetic and environmental risk factors, including gestational exposure to bisphenol A (BPA). BPA is an endocrine-disrupting chemical widely used in the synthesis of plastics and epoxy-resins. In 2012, the Food and Drug Administration issued a ban on the use of BPA in certain baby and childhood products, which contributed to the proliferation of BPA-free products. To make products without BPA, plastic and epoxy manufacturers often use chemical analogs, including bisphenol F (BPF) and bisphenol S (BPS). However, the structural and biochemical similarities BPF and BPS share with BPA suggest they may have similar molecular and cellular impacts on the developing nervous system, despite consumers generally regarding BPA-free products as safer alternatives. In this review, we synthesized all available peer-reviewed primary literature to date reporting on the neurodevelopmental impacts of BPF and/or BPS in animal models. In total, 61 papers were identified as relevant to the topic, including evaluation of BPF- and BPS-associated neurodevelopmental phenotypes such as changes in neurodevelopmental gene expression, the proliferation and differentiation of neural stem cells, synaptogenesis, central nervous system morphology, neuronal cell death, and behavior. Though less extensively studied than BPA, the collective works described here indicate that BPF and BPS can act as developmental neurotoxicants in animal models, urging further mechanistic and epidemiological analyses of these bisphenol analogs, as well as a reconsideration by regulatory agencies of policies surrounding their usage.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 263-280"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Infant cognitive home environment as a moderator for the association of prenatal lead on child language 婴儿认知家庭环境在产前铅对儿童语言的影响中的调节作用

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.010

Amanda C. Wylie , Michael T. Willoughby , Rebecca C. Fry , W. Roger Mills-Koonce , Sarah J. Short , Cathi B. Propper

{"title":"Infant cognitive home environment as a moderator for the association of prenatal lead on child language","authors":"Amanda C. Wylie , Michael T. Willoughby , Rebecca C. Fry , W. Roger Mills-Koonce , Sarah J. Short , Cathi B. Propper","doi":"10.1016/j.neuro.2025.04.010","DOIUrl":"10.1016/j.neuro.2025.04.010","url":null,"abstract":"<div><div>Exposure to lead during early life, including in pregnancy, is toxic to neurodevelopment. Though public health initiatives have resulted in an overall reduction in lead exposure levels, lead remains a significant environmental hazard, requiring innovative efforts to mitigate the burden of early life lead. This study explored whether positive postnatal social experiences in the forms of positive caregiving and a rich cognitive home environment moderate the associations of prenatal lead on child neurodevelopmental outcomes including language skills, effortful control, and executive function skills. We leverage an analytic sample (<em>N</em> = 107) drawn from a prospective cohort of mother-infant dyads. Prenatal lead was measured from maternal urine, positive caregiving from observational methods, and cognitive home environment from a validated questionnaire. Results reveal a negative association of prenatal lead on child language when the cognitive home environment in infancy was poor (<em>β</em>=-0.32, <em>p</em> = 0.04) but not when the cognitive home environment in infancy was rich (<em>β</em>=0.20, <em>p</em> = 0.16). This buffering effect was not observed for the child outcomes of effortful control or executive function skills. Our results encourage future research into the provision of a rich cognitive home environment as a means of mitigating the detrimental effects of prenatal lead exposure on early child language skills.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 306-317"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of developmental neurotoxicity of Dechlorane Plus, a recently identified persistent organic pollutant: An in silico study 最近发现的一种持久性有机污染物——十氯烷的发育神经毒性机制：一项硅研究

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-05-01 DOI: 10.1016/j.neuro.2025.04.013

Fuat Karakuş , Zübeyde Tanrıverdi , Burak Kuzu

{"title":"Mechanisms of developmental neurotoxicity of Dechlorane Plus, a recently identified persistent organic pollutant: An in silico study","authors":"Fuat Karakuş , Zübeyde Tanrıverdi , Burak Kuzu","doi":"10.1016/j.neuro.2025.04.013","DOIUrl":"10.1016/j.neuro.2025.04.013","url":null,"abstract":"<div><div>Dechlorane Plus (DP), a polychlorinated flame retardant, has recently been recognized as a persistent organic pollutant. In this study, the molecular mechanisms and targets associated with DP-induced developmental neurotoxicity (DNT) in humans were investigated through network toxicology, multi-level bioinformatics approaches, and molecular docking. Through comprehensive database analysis, 32 potential targets associated with DP-induced DNT were identified. Gene Ontology terms enrichment analysis revealed significant enrichment in pathways related to the nervous system processes, GABA-A receptor complex, and various binding and channel activities. KEGG pathway enrichment analysis indicated that DP-induced DNT is mediated through complex interactions involving neuroactive ligand-receptor interaction pathways. Further analysis using GeneMANIA, STRING, Cytoscape tools, and MCODE identified 11 hub targets, including GABRA1, GABRB1, GABRB3, and GABRG2 as key targets. Molecular docking revealed that DP binds to the GABRB3-GABRA1-GABRG2 protein complex to a degree comparable to the control bicuculline, a potent and selective antagonist of the GABA-A receptor. These findings suggest that DP may have antagonistic effects on the GABA-A receptor, potentially increasing neuronal excitability. This study offers valuable insights into the molecular mechanisms underlying DP-induced DNT and provides data for <em>in vitro</em> or <em>in vivo</em> studies.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 318-327"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Urolithin improves α-synuclein aggregation and DNMT1 expression in rotenone model of Parkinson’s disease 尿素改善鱼tenone帕金森病模型α-突触核蛋白聚集和DNMT1表达

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-04-23 DOI: 10.1016/j.neuro.2025.04.009

Ankita Devi , Sharon Munagalasetty , Pardeep Kumar , Rahul Kumar , Vasundhra Bhandari , Manoj P. Dandekar

{"title":"Urolithin improves α-synuclein aggregation and DNMT1 expression in rotenone model of Parkinson’s disease","authors":"Ankita Devi , Sharon Munagalasetty , Pardeep Kumar , Rahul Kumar , Vasundhra Bhandari , Manoj P. Dandekar","doi":"10.1016/j.neuro.2025.04.009","DOIUrl":"10.1016/j.neuro.2025.04.009","url":null,"abstract":"<div><div>α-synuclein aggregation is a key hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). We examined the multi-targeting effects of urolithin (UA, UB, UC, UD, UE, UM5, and UM6) against α-synuclein aggregation using an <em>in-silico</em> and <em>in-vitro</em> approach. For <em>in-silico</em> analysis, several potential targets were selected like 1XQ8 (α-synuclein monomer), 1H1D (catechol-o-methyltransferase), 2BK3 (monoamine oxidase-B), 3IAM (NADH dehydrogenase), 4I5I (Sirtuin-1), and 5WVO [DNA methyltransferase-1], which play key role in α-synuclein aggregation, levodopa degradation, and mitochondrial dysfunction. In protein-protein docking analysis, 5HF9 (acetylcholinesterase, AChE) was found to interact with 1XQ8 dimer, forming a more stable complex with two additional H-bonds and one salt bridge, which indicates AChE's role as a nucleator in α-synuclein aggregation. In ligand docking and molecular dynamic studies, urolithin-A (UA) formed a more stable complex with 1XQ8, 4I5I, and 5WVO compared to specific inhibitor 1XQ8-ZPD2 and specific activator 4I5I-resveratrol. While other urolithins (UE, UM5, UC, and UD) displayed a more stable complex with 5HF9, 2BK3, 1H1D, and 3IAM compared to specific inhibitor 5HF9-physostigmine, 2BK3-selegiline, 1H1D-BIA, and specific activator 3IAM-resveratrol complexes, respectively. The blood-brain barrier permeability of UA (QPlogBB: −0.97) was predicted to be more than levodopa (QPlogBB: −1.44) and less than rotenone (QPlogBB: 0.08). DNMT1 inhibitor (5-Aza-dC) and rotenone robustly decreased the DNMT1 and α-synuclein expression in Neuro 2 A cells which was significantly reversed by UA treatment at 31.25 µM concentration. These findings indicate the potential of urolithins, specifically UA, UC, UD, UE, and UM5 against α-synuclein aggregation.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 246-262"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of oral gestational particulate matter 10 exposure: Insights into neurodevelopmental milestones, inhibitory control, adult sociability, and object recognition 口服妊娠期颗粒物10暴露的影响：对神经发育里程碑、抑制控制、成人社交能力和物体识别的见解

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-04-17 DOI: 10.1016/j.neuro.2025.04.007

Diego Ruiz-Sobremazas , Mario Coca , Miguel Morales-Navas , Rocío Rodulfo-Cardenas , Caridad Lopez-Granero , Maria-Teresa Colomina , Cristian Perez-Fernandez , Fernando Sanchez-Santed

{"title":"The effects of oral gestational particulate matter 10 exposure: Insights into neurodevelopmental milestones, inhibitory control, adult sociability, and object recognition","authors":"Diego Ruiz-Sobremazas , Mario Coca , Miguel Morales-Navas , Rocío Rodulfo-Cardenas , Caridad Lopez-Granero , Maria-Teresa Colomina , Cristian Perez-Fernandez , Fernando Sanchez-Santed","doi":"10.1016/j.neuro.2025.04.007","DOIUrl":"10.1016/j.neuro.2025.04.007","url":null,"abstract":"<div><div>Air pollutants have been associated with various neurodevelopmental disorders, with several studies specifically linking Particulate Matter (PM) exposure to attentional and social deficits. This link is even more pronounced when exposure occurs during the prenatal period, as it can disrupt normal brain development. However, while social deficits have been extensively studied during adolescence, their impact on adult social behaviors remains largely unexplored. To investigate these effects, pregnant Wistar rats were exposed throughout gestation (GD1-GD21) to PM<sub>10</sub> at a dosage of 200 μg/Kg/day diluted in PBS that was freely drunk. After birth, the pups were evaluated on developmental milestones such as weight progression, ocular opening, and muscular strength. In adulthood, inhibitory control was assessed using the Five Choice Serial Reaction Time Task (5-CSRTT), social behavior using the Three-Chambered Crawley’s Test (3-CT), and object recognition using the Novelty Object Recognition test (NOR). The results indicated that prenatal PM10 exposure is associated with higher birth weight and poorer performance in neuromuscular tests. However, no significant differences were observed in inhibitory control (5-CSRTT) or social behavior (3-CT). Interestingly, prenatally exposed rodents showed heightened novelty responses in the NOR test. In conclusion, gestational exposure to PM<sub>10</sub> is related to differences in neurodevelopmental milestones, including weight and muscular strength. While it does not impact adult inhibitory control or social behavior, it influences novelty recognition in later life.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 231-245"},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β-Caryophyllene attenuates cadmium induced neurotoxicity in rats by modulating different cellular signaling pathways β-石竹烯通过调节不同的细胞信号通路减轻镉诱导的大鼠神经毒性

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-04-14 DOI: 10.1016/j.neuro.2025.04.006

Ismail Bolat , Serkan Yildirim , Yavuz Selim Saglam , Selim Comakli , Samet Teki̇n , Merve Bolat , Tuba Dogan , Metin Ki̇li̇cli̇oglu , Berrah Gozegi̇r

{"title":"β-Caryophyllene attenuates cadmium induced neurotoxicity in rats by modulating different cellular signaling pathways","authors":"Ismail Bolat , Serkan Yildirim , Yavuz Selim Saglam , Selim Comakli , Samet Teki̇n , Merve Bolat , Tuba Dogan , Metin Ki̇li̇cli̇oglu , Berrah Gozegi̇r","doi":"10.1016/j.neuro.2025.04.006","DOIUrl":"10.1016/j.neuro.2025.04.006","url":null,"abstract":"<div><div>Cadmium (Cd) is a naturally occurring harmful metal that can cause damage to many different tissues and organs in the body. Antioxidant agents are frequently utilized to counteract the harmful impact of this heavy metal on the body. This research explores the neuroprotective role of β-caryophyllene (BCP) in Cd-induced toxicity. Male Wistar rats were categorized into five groups: control, BCP400, Cd, BCP200 +Cd, and BCP400 +Cd. BCP suppressed Cd-induced oxidative damage in brain tissue by regulating the Nrf2/HO-1/SIRT1 signaling pathway. Moreover, BCP alleviates Cd-induced behavioral alterations through SIRT1 activation<del>.</del> Cd increased TNF-α and IL-1β levels and decreased IL-10 levels in brain tissue, whereas BCP suppressed TLR-4/NF-κB/JNK signaling pathway and restored these cytokines to normal levels. In addition, Cd exposure led to increased BAX and Caspase 3 and decreased Bcl-2 levels in neurons, but these proteins approached normal levels thanks to BCP's anti-apoptotic properties. Furthermore, while Beclin-1 and LC3A/B expression levels were increased in neurons of Cd-exposed animals, BCP suppressed these expressions by activating the PI3K/Akt/mTOR signaling pathway. Histopathological, biochemical, and molecular analyses confirmed BCP reduces oxidative stress, inflammation, apoptosis, and autophagy caused by Cd-induced neurotoxicity by regulating various signaling pathways and strengthening the antioxidant defense system. Therefore, we believe that BCP has a high potential as a therapeutic agent against Cd-induced neurotoxicity.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 206-217"},"PeriodicalIF":3.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thymoquinone-loaded solid lipid nanoparticles mitigate 3-Nitropropionic acid-induced mitochondrial dysfunction and oxidative damage via regulating PGC-1α/Nrf2 pathway 载胸腺醌的固体脂质纳米颗粒通过调节PGC-1α/Nrf2通路减轻3-硝基丙酸诱导的线粒体功能障碍和氧化损伤

IF 3.4 3区医学

Neurotoxicology Pub Date : 2025-04-12 DOI: 10.1016/j.neuro.2025.04.005

Surekha Ramachandran , Sumathi Thangarajan

{"title":"Thymoquinone-loaded solid lipid nanoparticles mitigate 3-Nitropropionic acid-induced mitochondrial dysfunction and oxidative damage via regulating PGC-1α/Nrf2 pathway","authors":"Surekha Ramachandran , Sumathi Thangarajan","doi":"10.1016/j.neuro.2025.04.005","DOIUrl":"10.1016/j.neuro.2025.04.005","url":null,"abstract":"<div><div>3-Nitropropionic acid (3-NP) is a mitochondrial toxin which causes bilateral striatal lesions in experimental animals, mimicking Huntington’s disease (HD) pathology. The molecular mechanisms underlying 3-NP-induced neuronal death involve mitochondrial dysfunction, transcriptional dysregulation, and impaired antioxidant defense systems. This study investigated the effects of thymoquinone (TQ) encapsulated in solid lipid nanoparticles (NanoTQ), on mitochondrial biogenesis in 3-NP-induced neurotoxicity in the striatum of male Wistar rats. Systemic administration of 3-NP (10 mg/kg) for 14 days inhibited mitochondrial complex enzymes and increased mitochondrial membrane permeability in the striatum. 3-NP exposure significantly altered the translational level of PGC-1α by modifying the expression of p-CREB/TORC1/SIRT1/PPARγ. Additionally, 3-NP exposure significantly reduced striatal levels of BDNF, GDNF, and their downstream effectors. Treatment with NanoTQ (10 and 20 mg/kg) and TQ (80 mg/kg) significantly (<em>P</em> < 0.01) increased mitochondrial complex enzyme activity compared to TQ (40 mg/kg). NanoTQ also significantly (<em>P</em> < 0.01) regulated the expression of regulatory proteins, promoting PGC-1α mediated mitochondrial biogenesis. Furthermore, NanoTQ restored BDNF and GDNF signaling and enhanced the antioxidant defense mechanism by increasing Nrf-2 and HO-1 expression while reducing Keap1 levels in the striatum. In conclusion, NanoTQ effectively mitigated 3-NP-induced neurotoxicity by regulating the mitochondrial biogenesis, neurotrophic factors, and antioxidant defense system, thereby preventing HD-like symptoms in rats.</div></div>","PeriodicalId":19189,"journal":{"name":"Neurotoxicology","volume":"108 ","pages":"Pages 191-205"},"PeriodicalIF":3.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0