Pub Date : 2024-11-15DOI: 10.1016/j.neuint.2024.105904
K M Bhargavi, Niya Gowthami, G K Chetan, M M Srinivas Bharath
Traumatic Brain Injury (TBI) is a global healthcare concern with considerable mortality and morbidity. Early diagnosis and timely treatment are critical for optimal clinical prognosis in TBI patients. Injury to the brain tissue following TBI is categorized into primary and secondary injury events, with the former being acute, while the latter evolves over a long period. Although surgical intervention is effective to treat primary injury, secondary injury events that could contribute to long term neurological deterioration, cognitive impairment and neurodegeneration do not have appropriate pharmacotherapy. To address this lacuna, studies based on modern medicine to explore novel drugs in TBI have met with limited success. This has led to focussed efforts to assess natural products capable of targeting multiple pathways in TBI. Complex natural mixtures and isolated phytochemicals capable of targeting redox mechanisms, neuroinflammation, mitochondrial dysfunction, cell death pathways and other specific targets etc. have been characterized. However, the field has met with certain limitations and challenges with inadequate clinical studies and trials being the most important concern. The current review provides an overview of the dietary factors, nutraceuticals, natural extracts, and phytochemicals that could be potentially applied in neuroprotection, TBI therapy and long-term management of cognitive symptoms and other neurological deficits.
{"title":"Neuroprotective effects of nutraceuticals and natural products in Traumatic Brain Injury.","authors":"K M Bhargavi, Niya Gowthami, G K Chetan, M M Srinivas Bharath","doi":"10.1016/j.neuint.2024.105904","DOIUrl":"https://doi.org/10.1016/j.neuint.2024.105904","url":null,"abstract":"<p><p>Traumatic Brain Injury (TBI) is a global healthcare concern with considerable mortality and morbidity. Early diagnosis and timely treatment are critical for optimal clinical prognosis in TBI patients. Injury to the brain tissue following TBI is categorized into primary and secondary injury events, with the former being acute, while the latter evolves over a long period. Although surgical intervention is effective to treat primary injury, secondary injury events that could contribute to long term neurological deterioration, cognitive impairment and neurodegeneration do not have appropriate pharmacotherapy. To address this lacuna, studies based on modern medicine to explore novel drugs in TBI have met with limited success. This has led to focussed efforts to assess natural products capable of targeting multiple pathways in TBI. Complex natural mixtures and isolated phytochemicals capable of targeting redox mechanisms, neuroinflammation, mitochondrial dysfunction, cell death pathways and other specific targets etc. have been characterized. However, the field has met with certain limitations and challenges with inadequate clinical studies and trials being the most important concern. The current review provides an overview of the dietary factors, nutraceuticals, natural extracts, and phytochemicals that could be potentially applied in neuroprotection, TBI therapy and long-term management of cognitive symptoms and other neurological deficits.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105904"},"PeriodicalIF":4.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646555","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}
Pub Date : 2024-11-13DOI: 10.1016/j.neuint.2024.105902
Xue Jiang , Yumei Wang , Zhaochen Lin , Chao Li , Qian Wang , Junyan Zhang , Xiuhua Liu , Ziye Li , Chao Cui
Neurodegenerative diseases (NDDs), as a neurological disorder characterised by neuronal degeneration and death, are a serious threat to human health and have long attracted attention due to their complex pathogenesis and the ineffectiveness of therapeutic drugs. Existing studies have shown that Polygonatum Sibiricum polysaccharides (PSP) have immunoregulatory, antioxidant, anti-inflammatory and other pharmacological effects, and their neuroprotective effects have been demonstrated in several scientific studies. This paper reviews the main pharmacological effects and mechanisms of PSP in the protection and treatment of NDDs, to provide a reference for the clinical application and basic research of PSP in NDDs.
{"title":"Polygonatum sibiricum polysaccharides: A promising strategy in the treatment of neurodegenerative disease","authors":"Xue Jiang , Yumei Wang , Zhaochen Lin , Chao Li , Qian Wang , Junyan Zhang , Xiuhua Liu , Ziye Li , Chao Cui","doi":"10.1016/j.neuint.2024.105902","DOIUrl":"10.1016/j.neuint.2024.105902","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs), as a neurological disorder characterised by neuronal degeneration and death, are a serious threat to human health and have long attracted attention due to their complex pathogenesis and the ineffectiveness of therapeutic drugs. Existing studies have shown that <em>Polygonatum Sibiricum</em> polysaccharides (PSP) have immunoregulatory, antioxidant, anti-inflammatory and other pharmacological effects, and their neuroprotective effects have been demonstrated in several scientific studies. This paper reviews the main pharmacological effects and mechanisms of PSP in the protection and treatment of NDDs, to provide a reference for the clinical application and basic research of PSP in NDDs.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105902"},"PeriodicalIF":4.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611479","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}
Pub Date : 2024-11-13DOI: 10.1016/j.neuint.2024.105901
Cheng Lei , Jiaqi Wang , Xiaoyu Zhang , Xuemin Ge , Wei Zhao , Xinrong Li , Wei Jiang , Mingyu Ma , Zhenhai Wang , Shanshan Sun , Qingfei Kong , Hulun Li , Lili Mu , Jinghua Wang
Neuronal differentiation and neurite growth are essential processes in nervous system development and are regulated by several factors. Although all-trans retinoic acid (ATRA) has been shown to mediate the differentiation of mouse neuroblastoma cells via the activation of several pathways, including Wnt/β-catenin signaling, the mechanism remains unclear. The pyruvate kinase, muscle (PKM) plays an important role in the glycolysis of neuroblastoma cells and regulates the Wnt signaling pathway in various cancer cells. In this study, we hypothesized that the Wnt/PKM axis regulates the differentiation of neuroblastoma cells (Neuro-2a and N1E-115). To test this hypothesis, we used inhibitors and activators of the Wnt/β-catenin and glycolytic pathways in ATRA-induced differentiated Neuro-2a and N1E-115 cells and established cell lines with silenced or a mutant replacement of Pkm. Western blot and qPCR showed that ATRA treatment activated the Wnt signaling pathway and inhibited PKM-mediated glycolysis. The oxygen consumption rate (indicating oxidative phosphorylation) significantly increased, whereas the extracellular acidification rate (indicating glycolysis) significantly decreased during differentiation; these effects were reversed upon PKM inhibition. The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression. Treatment with the Wnt activator kenpaullone promoted Neuro-2a and N1E-115 differentiation, which was reversed by ML-265 administration. These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation.
{"title":"The wnt/pyruvate kinase, muscle axis plays an essential role in the differentiation of mouse neuroblastoma cells","authors":"Cheng Lei , Jiaqi Wang , Xiaoyu Zhang , Xuemin Ge , Wei Zhao , Xinrong Li , Wei Jiang , Mingyu Ma , Zhenhai Wang , Shanshan Sun , Qingfei Kong , Hulun Li , Lili Mu , Jinghua Wang","doi":"10.1016/j.neuint.2024.105901","DOIUrl":"10.1016/j.neuint.2024.105901","url":null,"abstract":"<div><div>Neuronal differentiation and neurite growth are essential processes in nervous system development and are regulated by several factors. Although all-trans retinoic acid (ATRA) has been shown to mediate the differentiation of mouse neuroblastoma cells via the activation of several pathways, including Wnt/β-catenin signaling, the mechanism remains unclear. The pyruvate kinase, muscle (PKM) plays an important role in the glycolysis of neuroblastoma cells and regulates the Wnt signaling pathway in various cancer cells. In this study, we hypothesized that the Wnt/PKM axis regulates the differentiation of neuroblastoma cells (Neuro-2a and N1E-115). To test this hypothesis, we used inhibitors and activators of the Wnt/β-catenin and glycolytic pathways in ATRA-induced differentiated Neuro-2a and N1E-115 cells and established cell lines with silenced or a mutant replacement of Pkm. Western blot and qPCR showed that ATRA treatment activated the Wnt signaling pathway and inhibited PKM-mediated glycolysis. The oxygen consumption rate (indicating oxidative phosphorylation) significantly increased, whereas the extracellular acidification rate (indicating glycolysis) significantly decreased during differentiation; these effects were reversed upon PKM inhibition. The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression. Treatment with the Wnt activator kenpaullone promoted Neuro-2a and N1E-115 differentiation, which was reversed by ML-265 administration. These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105901"},"PeriodicalIF":4.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611483","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}
Pub Date : 2024-11-11DOI: 10.1016/j.neuint.2024.105899
Ingvild E Bjerke, Harry Carey, Jan G Bjaalie, Trygve B Leergaard, Jee Hyun Kim
The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages using validated transgenic mice expressing green fluorescent protein in cells producing D1 or D2 mRNA. After analyzing >4,500 coronal brain images, a cortico-subcortical shift in D1/D2 balance was discovered, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.
{"title":"The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation.","authors":"Ingvild E Bjerke, Harry Carey, Jan G Bjaalie, Trygve B Leergaard, Jee Hyun Kim","doi":"10.1016/j.neuint.2024.105899","DOIUrl":"https://doi.org/10.1016/j.neuint.2024.105899","url":null,"abstract":"<p><p>The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages using validated transgenic mice expressing green fluorescent protein in cells producing D1 or D2 mRNA. After analyzing >4,500 coronal brain images, a cortico-subcortical shift in D1/D2 balance was discovered, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"105899"},"PeriodicalIF":4.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611482","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}
Pub Date : 2024-11-08DOI: 10.1016/j.neuint.2024.105900
Chusana Mekhora , Daniel J. Lamport , Jeremy P.E. Spencer
Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.
{"title":"An overview of the relationship between inflammation and cognitive function in humans, molecular pathways and the impact of nutraceuticals","authors":"Chusana Mekhora , Daniel J. Lamport , Jeremy P.E. Spencer","doi":"10.1016/j.neuint.2024.105900","DOIUrl":"10.1016/j.neuint.2024.105900","url":null,"abstract":"<div><div>Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105900"},"PeriodicalIF":4.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611486","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}
Pub Date : 2024-11-08DOI: 10.1016/j.neuint.2024.105898
Ediandra Tissot Castro , Rafael Teixeira Ribeiro , Andrey Vinicios Soares Carvalho , Diorlon Nunes Machado , Ângela Beatris Zemniaçak , Rafael Palavro , Sâmela de Azevedo Cunha , Tailine Quevedo Tavares , Diogo Onofre Gomes de Souza , Carlos Alexandre Netto , Guilhian Leipnitz , Alexandre Umpierrez Amaral , Moacir Wajner
Patients with glutaric acidemia type I (GA I) manifest motor and intellectual disabilities whose pathogenesis has been so far poorly explored. Therefore, we evaluated neuromotor and cognitive abilities, as well as histopathological and immunohistochemical features in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase (GCDH) deficient knockout mice (Gcdh−/−), a well-recognized model of GA I. The effects of a single intracerebroventricular glutaric acid (GA) injection in one-day-old pups on the same neurobehavioral and histopathological/immunohistochemical endpoints were also investigated. Seven-day-old Gcdh−/− mice presented altered gait, whereas those receiving a GA neonatal administration manifested other sensorimotor deficits, including an abnormal response to negative geotaxis, cliff aversion and righting reflex, and muscle tone impairment. Compared to the WT mice, adult Gcdh−/− mice exhibited motor impairment, evidenced by poor performance in the Rota-rod test. Furthermore, neonatal GA administration provoked long-standing short- and long-term memory impairment in adult Gcdh−/− mice. Regarding the histopathological features, a significant increase in vacuoles and neurodegenerative cells was observed in both the cerebral cortex and striatum of 15- and 60-day-old Gcdh−/− mice and was more pronounced in mice injected with GA. Neuronal loss (decrease of NeuN staining) was also significantly increased in the cerebral cortex and striatum of Gcdh−/− mice, particularly in those neonatally injected with GA. In contrast, immunohistochemistry of MBP, astrocytic proteins GFAP and S100B, and the microglial marker Iba1 was not changed in 60-day-old Gcdh−/− mice, suggesting no myelination disturbance, reactive astrogliosis, and microglia activation, respectively. These data highlight the neurotoxicity of GA and the importance of early treatment aiming to decrease GA accumulation at early stages of development to prevent brain damage and learning/memory disabilities in GA I patients.
戊二酸血症 I 型（GA I）患者表现为运动和智力障碍，其发病机制迄今为止尚未得到深入研究。因此，我们评估了谷草酰-CoA脱氢酶（GCDH）缺陷基因敲除小鼠（Gcdh-/-）的神经运动和认知能力以及大脑皮层和纹状体的组织病理学和免疫组化特征。我们还研究了对出生一天的幼鼠脑室内注射一次戊二酸（GA）对相同的神经行为和组织病理学/免疫组化终点的影响。七日龄的 Gcdh-/- 小鼠步态发生改变，而那些接受 GA 新生儿给药的小鼠则表现出其他感觉运动缺陷，包括对负向地轴、悬崖厌恶和向右转反射的异常反应，以及肌张力损伤。与 WT 小鼠相比，成年 Gcdh-/- 小鼠表现出运动障碍，这体现在罗盘杆试验中的不良表现。此外，新生儿给予GA会引起成年Gcdh-/-小鼠长期的短期和长期记忆障碍。在组织病理学特征方面，在15天和60天大的Gcdh-/-小鼠的大脑皮层和纹状体中都观察到空泡和神经退行性细胞显著增加，在注射GA的小鼠中更为明显。在 Gcdh-/- 小鼠的大脑皮层和纹状体中，神经元丢失（NeuN 染色减少）也显著增加，尤其是在新生儿注射 GA 的小鼠中。与此相反，在 60 天大的 Gcdh-/- 小鼠中，MBP、星形胶质细胞蛋白 GFAP 和 S100B 以及小胶质细胞标记物 Iba1 的免疫组化结果没有变化，这分别表明没有髓鞘化紊乱、反应性星形胶质细胞增生和小胶质细胞活化。这些数据突显了GA的神经毒性以及早期治疗的重要性，早期治疗旨在减少GA在发育早期的积累，以防止GA I患者的脑损伤和学习/记忆障碍。
{"title":"Impairment of neuromotor development and cognition associated with histopathological and neurochemical abnormalities in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase deficient mice","authors":"Ediandra Tissot Castro , Rafael Teixeira Ribeiro , Andrey Vinicios Soares Carvalho , Diorlon Nunes Machado , Ângela Beatris Zemniaçak , Rafael Palavro , Sâmela de Azevedo Cunha , Tailine Quevedo Tavares , Diogo Onofre Gomes de Souza , Carlos Alexandre Netto , Guilhian Leipnitz , Alexandre Umpierrez Amaral , Moacir Wajner","doi":"10.1016/j.neuint.2024.105898","DOIUrl":"10.1016/j.neuint.2024.105898","url":null,"abstract":"<div><div>Patients with glutaric acidemia type I (GA I) manifest motor and intellectual disabilities whose pathogenesis has been so far poorly explored. Therefore, we evaluated neuromotor and cognitive abilities, as well as histopathological and immunohistochemical features in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase (GCDH) deficient knockout mice (<em>Gcdh</em><sup><em>−/−</em></sup>), a well-recognized model of GA I. The effects of a single intracerebroventricular glutaric acid (GA) injection in one-day-old pups on the same neurobehavioral and histopathological/immunohistochemical endpoints were also investigated. Seven-day-old <em>Gcdh</em><sup><em>−/−</em></sup> mice presented altered gait, whereas those receiving a GA neonatal administration manifested other sensorimotor deficits, including an abnormal response to negative geotaxis, cliff aversion and righting reflex, and muscle tone impairment. Compared to the WT mice, adult <em>Gcdh−/−</em> mice exhibited motor impairment, evidenced by poor performance in the Rota-rod test. Furthermore, neonatal GA administration provoked long-standing short- and long-term memory impairment in adult <em>Gcdh</em><sup><em>−/−</em></sup> mice. Regarding the histopathological features, a significant increase in vacuoles and neurodegenerative cells was observed in both the cerebral cortex and striatum of 15- and 60-day-old Gcd<em>h−/−</em> mice and was more pronounced in mice injected with GA. Neuronal loss (decrease of NeuN staining) was also significantly increased in the cerebral cortex and striatum of <em>Gcdh</em><sup><em>−/−</em></sup> mice, particularly in those neonatally injected with GA. In contrast, immunohistochemistry of MBP, astrocytic proteins GFAP and S100B, and the microglial marker Iba1 was not changed in 60-day-old Gcdh−/− mice, suggesting no myelination disturbance, reactive astrogliosis, and microglia activation, respectively. These data highlight the neurotoxicity of GA and the importance of early treatment aiming to decrease GA accumulation at early stages of development to prevent brain damage and learning/memory disabilities in GA I patients.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105898"},"PeriodicalIF":4.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611499","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}
Pub Date : 2024-11-06DOI: 10.1016/j.neuint.2024.105897
Ashmita Das , Vikas Rajput , Durlav Chowdhury , Rajesh Choudhary , Surendra H. Bodakhe
Alzheimer's disease (AD) is a neurodegenerative disorder that is the fifth most common cause of mortality worldwide and the second most common cause of death in developed countries. The etiology of AD remains poorly understood; however, it is correlated with the accumulation of proteins in the brain, ultimately leading to cellular damage. Multiple factors, including genetic and environmental factors such as chemicals or food, have been linked to protein aggregation and cell death in AD. Boron is a vital micronutrient that is necessary for plant growth and is abundantly present in various fruits and nuts. Prior research has emphasized the importance of boron as a neuroprotective agent and necessary component for the preservation of brain health and function. However, the precise function of boron in the brain remains poorly understood. This review elucidates the molecular role of boron in the brain by examining existing information about its impact on neurodegenerative diseases and may provide a deeper understanding of the etiology of AD and, ultimately, lead to the development of novel approaches for its treatment.
{"title":"Boron: An intriguing factor in retarding Alzheimer's progression","authors":"Ashmita Das , Vikas Rajput , Durlav Chowdhury , Rajesh Choudhary , Surendra H. Bodakhe","doi":"10.1016/j.neuint.2024.105897","DOIUrl":"10.1016/j.neuint.2024.105897","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder that is the fifth most common cause of mortality worldwide and the second most common cause of death in developed countries. The etiology of AD remains poorly understood; however, it is correlated with the accumulation of proteins in the brain, ultimately leading to cellular damage. Multiple factors, including genetic and environmental factors such as chemicals or food, have been linked to protein aggregation and cell death in AD. Boron is a vital micronutrient that is necessary for plant growth and is abundantly present in various fruits and nuts. Prior research has emphasized the importance of boron as a neuroprotective agent and necessary component for the preservation of brain health and function. However, the precise function of boron in the brain remains poorly understood. This review elucidates the molecular role of boron in the brain by examining existing information about its impact on neurodegenerative diseases and may provide a deeper understanding of the etiology of AD and, ultimately, lead to the development of novel approaches for its treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105897"},"PeriodicalIF":4.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611497","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}
Pub Date : 2024-11-02DOI: 10.1016/j.neuint.2024.105896
Jin-Sun Park , Yea-Hyun Leem , Do-Yeon Kim , Jae-Min Park , Seong-Eun Kim , Hee-Sun Kim
Parkinson's disease (PD) is a neurodegenerative disorder triggered by the loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have demonstrated that necroptosis is involved in dopaminergic neuronal cell death and the resulting neuroinflammation. During the process of necroptosis, a necrosome complex is formed consisting of the proteins receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Although the neuroprotective effects of the RIPK1-specific inhibitor necrostatin-1, as well as RIPK3 and MLKL knockout in mice, have been described, the effects of RIPK3 pharmacological inhibitors have not yet been reported in animal models of PD. In the present study, we investigated the neuroprotective effects of GSK872, a specific RIPK3 inhibitor, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. GSK872 rescued MPTP-induced motor impairment and inhibited tyrosine hydroxylase-positive dopaminergic cell death in the SN and striatum. Additionally, GSK872 inhibited the MPTP-induced increase in the expression of p-RIPK3 and p-MLKL in both the dopaminergic neurons and microglia, as assessed by biochemical and histological analyses. GSK872 further inhibited microglial activation and the expression of inflammatory mediators including NLRP3, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in the SN region of MPTP mice. Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.
{"title":"Neuroprotective and anti-inflammatory effects of the RIPK3 inhibitor GSK872 in an MPTP-induced mouse model of Parkinson's disease","authors":"Jin-Sun Park , Yea-Hyun Leem , Do-Yeon Kim , Jae-Min Park , Seong-Eun Kim , Hee-Sun Kim","doi":"10.1016/j.neuint.2024.105896","DOIUrl":"10.1016/j.neuint.2024.105896","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder triggered by the loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have demonstrated that necroptosis is involved in dopaminergic neuronal cell death and the resulting neuroinflammation. During the process of necroptosis, a necrosome complex is formed consisting of the proteins receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Although the neuroprotective effects of the RIPK1-specific inhibitor necrostatin-1, as well as RIPK3 and MLKL knockout in mice, have been described, the effects of RIPK3 pharmacological inhibitors have not yet been reported in animal models of PD. In the present study, we investigated the neuroprotective effects of GSK872, a specific RIPK3 inhibitor, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. GSK872 rescued MPTP-induced motor impairment and inhibited tyrosine hydroxylase-positive dopaminergic cell death in the SN and striatum. Additionally, GSK872 inhibited the MPTP-induced increase in the expression of <em>p</em>-RIPK3 and <em>p</em>-MLKL in both the dopaminergic neurons and microglia, as assessed by biochemical and histological analyses. GSK872 further inhibited microglial activation and the expression of inflammatory mediators including NLRP3, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in the SN region of MPTP mice. Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105896"},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566765","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}
Pub Date : 2024-10-24DOI: 10.1016/j.neuint.2024.105895
Zdenko Pirník , Ivan Szadvári , Veronika Borbélyová , Aleksandra Tomova
Autism spectrum disorder (ASD) is a neurodevelopmental disorder accompanied by narrow interests, difficulties in communication and social interaction, and repetitive behavior. In addition, ASD is frequently associated with eating and feeding problems. Although the symptoms of ASD are more likely to be observed in boys, the prevalence of eating disorders is more common in females. The ingestive behavior is regulated by the integrative system of the brain, which involves both homeostatic and hedonic neural circuits. Sex differences in the physiology of food intake depend on sex hormones regulating the expression of the ASD-associated Shank genes. Shank3 mutation leads to ASD-like traits and Shank3B −/− mice have been established as an animal model to study the neurobiology of ASD. Therefore, the long-lasting neuronal activity in the central neural circuit related to the homeostatic and hedonic regulation of food intake was evaluated in both sexes of Shank3B mice, followed by the evaluation of the food intake and preference. In the Shank3B +/+ genotype, well-preserved relationships in the tonic activity within the homeostatic neural network together with the relationships between ingestion and hedonic preference were observed in males but were reduced in females. These interrelations were partially or completely lost in the mice with the Shank3B −/− genotype. A decreased hedonic preference for the sweet taste but increased total food intake was found in the Shank3B −/− mice. In the Shank3B −/− group, there were altered sex differences related to the amount of tonic cell activity in the hedonic and homeostatic neural networks, together with altered sex differences in sweet and sweet-fat solution intake. Furthermore, the Shank3B −/− females exhibited an increased intake and preference for cheese compared to the Shank3B +/+ ones. The obtained data indicate altered functional crosstalk between the central homeostatic and hedonic neural circuits involved in the regulation of food intake in ASD.
{"title":"Altered sex differences related to food intake, hedonic preference, and FosB/deltaFosB expression within central neural circuit involved in homeostatic and hedonic food intake regulation in Shank3B mouse model of autism spectrum disorder","authors":"Zdenko Pirník , Ivan Szadvári , Veronika Borbélyová , Aleksandra Tomova","doi":"10.1016/j.neuint.2024.105895","DOIUrl":"10.1016/j.neuint.2024.105895","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder accompanied by narrow interests, difficulties in communication and social interaction, and repetitive behavior. In addition, ASD is frequently associated with eating and feeding problems. Although the symptoms of ASD are more likely to be observed in boys, the prevalence of eating disorders is more common in females. The ingestive behavior is regulated by the integrative system of the brain, which involves both homeostatic and hedonic neural circuits. Sex differences in the physiology of food intake depend on sex hormones regulating the expression of the ASD-associated Shank genes. Shank3 mutation leads to ASD-like traits and Shank3B −/− mice have been established as an animal model to study the neurobiology of ASD. Therefore, the long-lasting neuronal activity in the central neural circuit related to the homeostatic and hedonic regulation of food intake was evaluated in both sexes of Shank3B mice, followed by the evaluation of the food intake and preference. In the Shank3B +/+ genotype, well-preserved relationships in the tonic activity within the homeostatic neural network together with the relationships between ingestion and hedonic preference were observed in males but were reduced in females. These interrelations were partially or completely lost in the mice with the Shank3B −/− genotype. A decreased hedonic preference for the sweet taste but increased total food intake was found in the Shank3B −/− mice. In the Shank3B −/− group, there were altered sex differences related to the amount of tonic cell activity in the hedonic and homeostatic neural networks, together with altered sex differences in sweet and sweet-fat solution intake. Furthermore, the Shank3B −/− females exhibited an increased intake and preference for cheese compared to the Shank3B +/+ ones. The obtained data indicate altered functional crosstalk between the central homeostatic and hedonic neural circuits involved in the regulation of food intake in ASD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105895"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492290","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}
Pub Date : 2024-10-23DOI: 10.1016/j.neuint.2024.105890
Meritxell Deulofeu , Eladia M. Peña-Méndez , Petr Vaňhara , Josef Havel , Lukáš Moráň , Lukáš Pečinka , Anna Bagó-Mas , Enrique Verdú , Victoria Salvadó , Pere Boadas-Vaello
Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.
{"title":"Discriminating fingerprints of chronic neuropathic pain following spinal cord injury using artificial neural networks and mass spectrometry analysis of female mice serum","authors":"Meritxell Deulofeu , Eladia M. Peña-Méndez , Petr Vaňhara , Josef Havel , Lukáš Moráň , Lukáš Pečinka , Anna Bagó-Mas , Enrique Verdú , Victoria Salvadó , Pere Boadas-Vaello","doi":"10.1016/j.neuint.2024.105890","DOIUrl":"10.1016/j.neuint.2024.105890","url":null,"abstract":"<div><div>Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105890"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492291","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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