Neurotoxicity Research最新文献_第8页

BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology. BIN1在推翻阿尔茨海默氏症统治中的作用：对淀粉样蛋白和Tau神经病理学的影响。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-10-17 DOI: 10.1007/s12640-023-00670-3

Ishnoor Kaur, Tapan Behl, G Sundararajan, P Panneerselvam, A R Vijayakumar, G P Senthilkumar, T Venkatachalam, Dharmender Jaglan, Shivam Yadav, Khalid Anwer, Neeraj Kumar Fuloria, Aayush Sehgal, Monica Gulati, Sridevi Chigurupati

{"title":"BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.","authors":"Ishnoor Kaur, Tapan Behl, G Sundararajan, P Panneerselvam, A R Vijayakumar, G P Senthilkumar, T Venkatachalam, Dharmender Jaglan, Shivam Yadav, Khalid Anwer, Neeraj Kumar Fuloria, Aayush Sehgal, Monica Gulati, Sridevi Chigurupati","doi":"10.1007/s12640-023-00670-3","DOIUrl":"10.1007/s12640-023-00670-3","url":null,"abstract":"Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"698-707"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237148","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

Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel. 橙皮苷对stz诱导的糖尿病神经病变坐骨神经损伤的影响:TRPM2通道的调节。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-07-13 DOI: 10.1007/s12640-023-00657-0

Mehmet Hafit Bayir, Kenan Yıldızhan, Fikret Altındağ

{"title":"Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel.","authors":"Mehmet Hafit Bayir, Kenan Yıldızhan, Fikret Altındağ","doi":"10.1007/s12640-023-00657-0","DOIUrl":"10.1007/s12640-023-00657-0","url":null,"abstract":"Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"638-647"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764331","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: 2

Effect of Quinolinic Acid on Behavior, Morphology, and Expression of Inflammatory/oxidative Status in Rats' Striatum: Is Coenzyme Q₁₀ a Good Protector? 喹啉酸对大鼠纹状体行为、形态和炎症/氧化状态表达的影响:辅酶Q10是一个很好的保护剂吗?

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-07-29 DOI: 10.1007/s12640-023-00656-1

Fernanda Silva Ferreira, Osmar Vieira Ramires Junior, Tiago Marcon Dos Santos, Josiane Silva Silveira, Bruna Ferrary Deniz, Vinícius Santos Alves, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio, Angela T S Wyse

{"title":"Effect of Quinolinic Acid on Behavior, Morphology, and Expression of Inflammatory/oxidative Status in Rats' Striatum: Is Coenzyme Q10 a Good Protector?","authors":"Fernanda Silva Ferreira, Osmar Vieira Ramires Junior, Tiago Marcon Dos Santos, Josiane Silva Silveira, Bruna Ferrary Deniz, Vinícius Santos Alves, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio, Angela T S Wyse","doi":"10.1007/s12640-023-00656-1","DOIUrl":"10.1007/s12640-023-00656-1","url":null,"abstract":"Quinolinic acid (QUIN) is a toxic compound with pro-oxidant, pro-inflammatory, and pro-apoptotic actions found at high levels in the central nervous system (CNS) in several pathological conditions. Due to the toxicity of QUIN, it is important to evaluate strategies to protect against the damage caused by this metabolite in the brain. In this context, coenzyme Q10 (CoQ10) is a provitamin present in the mitochondria with a protective role in cells through several mechanisms of action. Based on these, the present study was aimed at evaluating the possible neuroprotective role of CoQ10 against damage caused by QUIN in the striatum of young Wistar rats. Twenty-one-day-old rats underwent a 10-day pretreatment with CoQ10 or saline (control) intraperitoneal injections and on the 30th day of life received QUIN intrastriatal or saline (control) administration. The animals were submitted to behavior tests or euthanized, and the striatum was dissected to neurochemical studies. Results showed that CoQ10 was able to prevent behavioral changes (the open field, object recognition, and pole test tasks) and neurochemical parameters (alteration in the gene expression of IL-1β, IL-6, SOD, and GPx, as well as in the immunocontent of cytoplasmic Nrf2 and nuclear p-Nf-κβ) caused by QUIN. These findings demonstrate the promising therapeutic effects of CoQ10 against QUIN toxicity.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"559-570"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889530","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

Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease. 线粒体功能障碍作为主要神经退行性疾病治疗干预的信号靶点。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-05-10 DOI: 10.1007/s12640-023-00647-2

Shubhada V Mangrulkar, Nitu L Wankhede, Mayur B Kale, Aman B Upaganlawar, Brijesh G Taksande, Milind J Umekar, Md Khalid Anwer, Hamad Ghaleb Dailah, Syam Mohan, Tapan Behl

{"title":"Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.","authors":"Shubhada V Mangrulkar, Nitu L Wankhede, Mayur B Kale, Aman B Upaganlawar, Brijesh G Taksande, Milind J Umekar, Md Khalid Anwer, Hamad Ghaleb Dailah, Syam Mohan, Tapan Behl","doi":"10.1007/s12640-023-00647-2","DOIUrl":"10.1007/s12640-023-00647-2","url":null,"abstract":"Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"708-729"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494013","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: 6

Biological Pathways Associated with Vitamins in Autism Spectrum Disorder. 自闭症谱系障碍中与维生素相关的生物学途径。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-10-21 DOI: 10.1007/s12640-023-00674-z

Darlan Gusso, Gustavo Ricardo Krupp Prauchner, Alessandra Schmitt Rieder, Angela T S Wyse

{"title":"Biological Pathways Associated with Vitamins in Autism Spectrum Disorder.","authors":"Darlan Gusso, Gustavo Ricardo Krupp Prauchner, Alessandra Schmitt Rieder, Angela T S Wyse","doi":"10.1007/s12640-023-00674-z","DOIUrl":"10.1007/s12640-023-00674-z","url":null,"abstract":"Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca2+ levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"730-740"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680332","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

Metergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen. Metergoline与通过基因表达特征筛选鉴定的非典型抗精神病药物具有相同的性质。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-11-03 DOI: 10.1007/s12640-023-00673-0

Chiara C Bortolasci, Emily J Jaehne, Damián Hernández, Briana Spolding, Timothy Connor, Bruna Panizzutti, Olivia M Dean, Tamsyn M Crowley, Alison R Yung, Laura Gray, Jee Hyun Kim, Maarten van den Buuse, Michael Berk, Ken Walder

{"title":"Metergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen.","authors":"Chiara C Bortolasci, Emily J Jaehne, Damián Hernández, Briana Spolding, Timothy Connor, Bruna Panizzutti, Olivia M Dean, Tamsyn M Crowley, Alison R Yung, Laura Gray, Jee Hyun Kim, Maarten van den Buuse, Michael Berk, Ken Walder","doi":"10.1007/s12640-023-00673-0","DOIUrl":"10.1007/s12640-023-00673-0","url":null,"abstract":"Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"502-513"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glial Activation, Mitochondrial Imbalance, and Akt/mTOR Signaling May Be Potential Mechanisms of Cognitive Impairment in Heart Failure Mice. 神经胶质激活、线粒体失衡和Akt/mTOR信号传导可能是心力衰竭小鼠认知功能障碍的潜在机制。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-09-05 DOI: 10.1007/s12640-023-00655-2

Yanan Wu, Kaiyi Zhou, Baiyang Liu, Jindong Xu, Liming Lei, Jiaqi Hu, Xiao Cheng, Feng Zhong, Sheng Wang

{"title":"Glial Activation, Mitochondrial Imbalance, and Akt/mTOR Signaling May Be Potential Mechanisms of Cognitive Impairment in Heart Failure Mice.","authors":"Yanan Wu, Kaiyi Zhou, Baiyang Liu, Jindong Xu, Liming Lei, Jiaqi Hu, Xiao Cheng, Feng Zhong, Sheng Wang","doi":"10.1007/s12640-023-00655-2","DOIUrl":"10.1007/s12640-023-00655-2","url":null,"abstract":"Heart failure (HF) is a major health burden worldwide, with approximately half of HF patients having a comorbid cognitive impairment (CI). However, it is still unclear how CI develops in patients with HF. In the present study, a mice model of heart failure was established by ligating the left anterior descending coronary artery. Echocardiography 1 month later confirmed the decline in ejection fraction and ventricular remodeling. Cognitive function was examined by the Pavlovian fear conditioning and the Morris water maze. HF group cued fear memory, spatial memory, and learning impairment, accompanied by activation of glial cells (astrocytes, microglia, and oligodendrocytes) in the hippocampus. In addition, the mitochondrial biogenesis genes TFAM and SIRT1 decreased, and the fission gene DRP1 increased in the hippocampus. Damaged mitochondria release excessive ROS, and the ability to produce ATP decreases. Damaged swollen mitochondria with altered morphology and aberrant inner-membrane crista were observed under a transmission electron microscope. Finally, Akt/mTOR signaling was upregulated in the hippocampus of heart failure mice. These findings suggest that activation of Akt/mTOR signaling, glial activation, and mitochondrial dynamics imbalance could trigger cognitive impairment in the pathological process of heart failure mice.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"589-603"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154499","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

Bumetanide Attenuates Cognitive Deficits and Brain Damage in Rats Subjected to Hypoxia-Ischemia at Two Time Points of the Early Postnatal Period. 布美他尼减轻产后早期两个时间点缺氧缺血大鼠的认知缺陷和脑损伤。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-06-28 DOI: 10.1007/s12640-023-00654-3

Diorlon Nunes Machado, Luz Elena Durán-Carabali, Felipe Kawa Odorcyk, Andrey Vinicios Soares Carvalho, Ana Paula Rodrigues Martini, Livia Machado Schlemmer, Marcel de Medeiros de Mattos, Gabriel Pereira Bernd, Carla Dalmaz, Carlos Alexandre Netto

{"title":"Bumetanide Attenuates Cognitive Deficits and Brain Damage in Rats Subjected to Hypoxia-Ischemia at Two Time Points of the Early Postnatal Period.","authors":"Diorlon Nunes Machado, Luz Elena Durán-Carabali, Felipe Kawa Odorcyk, Andrey Vinicios Soares Carvalho, Ana Paula Rodrigues Martini, Livia Machado Schlemmer, Marcel de Medeiros de Mattos, Gabriel Pereira Bernd, Carla Dalmaz, Carlos Alexandre Netto","doi":"10.1007/s12640-023-00654-3","DOIUrl":"10.1007/s12640-023-00654-3","url":null,"abstract":"Neonatal hypoxia-ischemia (HI) is one of the main causes of tissue damage, cell death, and imbalance between neuronal excitation and inhibition and synaptic loss in newborns. GABA, the major inhibitory neurotransmitter of the central nervous system (CNS) in adults, is excitatory at the onset of neurodevelopment and its action depends on the chloride (Cl-) cotransporters NKCC1 (imports Cl-) and KCC2 (exports Cl-) expression. Under basal conditions, the NKCC1/KCC2 ratio decreases over neurodevelopment. Thus, changes in this ratio caused by HI may be related to neurological disorders. The present study evaluated the effects of bumetanide (NKCC cotransporters inhibitor) on HI impairments in two neurodevelopmental periods. Male Wistar rat pups, 3 (PND3) and 11 (PND11) days old, were submitted to the Rice-Vannucci model. Animals were divided into 3 groups: SHAM, HI-SAL, and HI-BUM, considering each age. Bumetanide was administered intraperitoneally at 1, 24, 48, and 72 h after HI. NKCC1, KCC2, PSD-95, and synaptophysin proteins were analyzed after the last injection by western blot. Negative geotaxis, righting reflex, open field, object recognition test, and Morris water maze task were performed to assess neurological reflexes, locomotion, and memory function. Tissue atrophy and cell death were evaluated by histology. Bumetanide prevented neurodevelopmental delay, hyperactivity, and declarative and spatial memory deficits. Furthermore, bumetanide reversed HI-induced brain tissue damage, reduced neuronal death and controlled GABAergic tone, maintained the NKCC1/KCC2 ratio, and synaptogenesis close to normality. Thereby, bumetanide appears to play an important therapeutic role in the CNS, protecting the animals against HI damage and improving functional performance.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"526-545"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696426","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

Physical Exercise Promotes Beneficial Changes on Neurotrophic Factors in Mesolimbic Brain Areas After AMPH Relapse: Involvement of the Endogenous Opioid System. 体育锻炼促进AMPH复发后大脑中边缘区神经营养因子的有益变化：内源性阿片系统的参与。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1007/s12640-023-00675-y

Rosa H Z, Segat H J, Barcelos R C S, Roversi Kr, Rossato D R, Burger M E

{"title":"Physical Exercise Promotes Beneficial Changes on Neurotrophic Factors in Mesolimbic Brain Areas After AMPH Relapse: Involvement of the Endogenous Opioid System.","authors":"Rosa H Z, Segat H J, Barcelos R C S, Roversi Kr, Rossato D R, Burger M E","doi":"10.1007/s12640-023-00675-y","DOIUrl":"10.1007/s12640-023-00675-y","url":null,"abstract":"Addiction is a serious public health problem, and the current pharmacotherapy is unable to prevent drug use reinstatement. Studies have focused on physical exercise as a promising coadjuvant treatment. Our research group recently showed beneficial neuroadaptations in the dopaminergic system related to amphetamine-relapse prevention involving physical exercise-induced endogenous opioid system activation (EXE-OS activation). In this context, additional mechanisms were explored to understand the exercise benefits on drug addiction. Male rats previously exposed to amphetamine (AMPH, 4.0 mg/kg) for 8 days were submitted to physical exercise for 5 weeks. EXE-OS activation was blocked by naloxone administration (0.3 mg/kg) 5 min before each physical exercise session. After the exercise protocol, the rats were re-exposed to AMPH for 3 days, and in sequence, euthanasia was performed and the VTA and NAc were dissected. In the VTA, our findings showed increased immunocontent of proBDNF, BDNF, and GDNF and decreased levels of AMPH-induced TrkB; therefore, EXE-OS activation increased all these markers and naloxone administration prevented this exercise-induced effect. In the NAc, the same molecular markers were also increased by AMPH and decreased by EXE-OS activation. In this study, we propose a close relation between EXE-OS activation beneficial influence and a consequent neuroadaptation on neurotrophins and dopaminergic system levels in the mesolimbic brain area, preventing the observed AMPH-relapse behavior. Our outcomes bring additional knowledge concerning addiction neurobiology understanding and show that EXE-OS activation may be a potential adjuvant tool in drug addiction therapy.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"741-751"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413296","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 Carvacrol on Transient Receptor Potential (TRP) Channels in an Animal Model of Parkinson's Disease. 香芹酚对帕金森病动物模型瞬时受体电位通道的影响

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-07-15 DOI: 10.1007/s12640-023-00660-5

Tülay Akan, Yasemin Aydın, Orhan Tansel Korkmaz, Emel Ulupınar, Faruk Saydam

{"title":"The Effects of Carvacrol on Transient Receptor Potential (TRP) Channels in an Animal Model of Parkinson's Disease.","authors":"Tülay Akan, Yasemin Aydın, Orhan Tansel Korkmaz, Emel Ulupınar, Faruk Saydam","doi":"10.1007/s12640-023-00660-5","DOIUrl":"10.1007/s12640-023-00660-5","url":null,"abstract":"In this study, we aimed to investigate the effects of carvacrol (CA), a widely used phytochemical having anti-oxidant and neuroprotective effects, on transient receptor potential (TRP) channels in an animal model of Parkinson's disease (PD). A total of 64 adult male Spraque-Dawley rats were divided into four groups: sham-operated, PD animal model (unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA), 6 µg/µl), PD + vehicle (dimethyl sulfoxide (DMSO)) treatment, and PD + CA treatment (10 mg/kg, every other day, for 14 days). Half of the brain samples of substantia nigra pars compacta (SNpc) and striatum (CPu) were collected for immunohistochemistry and the remaining half were used for molecular analyses. CA treatment significantly increased the density of dopaminergic neurons immunolabeled with tyrosine hydroxylase and transient receptor potential canonical 1 (TRPC1) channel in the SNpc of PD animals. In contrast, the density of astrocytes immunolabeled with glial fibrillary acetic acid and transient receptor potential ankyrin 1 (TRPA1) channel significantly decreased following CA treatment in the CPu of PD animals. RT-PCR and western blot analyses showed that 6-OHDA administration significantly reduced TRPA1 and TPRPC1 mRNA expression and protein levels in both SNpc and CPu. CA treatment significantly upregulated TRPA1 expression in PD group, while TRPC1 levels did not display an alteration. Based on this data it was concluded that CA treatment might protect the number of dopaminergic neurons by reducing the reactive astrogliosis and modulating the expression of TRP channels in both neurons and astrocytes in an animal model of PD.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":" ","pages":"660-669"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9776658","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}

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