Pub Date : 2025-02-06DOI: 10.1016/j.neuroscience.2024.12.021
Inga Kristaponyte , Nichole L Beebe , Nikhil Harish, Brett R Schofield, Alex V Galazyuk
Metabotropic glutamate receptors (mGluRs) are widely expressed throughout the central nervous system. They are linked to G-protein coupled receptors and are known to modulate synaptic transmission. The data regarding their expression in auditory structures are not systematic and mainly originate from physiological studies where expression was used to support physiological findings. MGluRs are classified into three groups based on their sequence homology, G protein-coupling, and ligand selectivity. Our recent physiological findings made us focus on the group II mGluRs. The objective of this study was to characterize group II mGluR expression, and whether it changes in aged brains, in three central auditory structures: inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). We performed immunostaining experiments followed by optical density quantification in young and old mice. We found group II mGluR staining in the IC, MG, and AC. However, the intensity of this staining was not uniform within these auditory structures. In the IC expression was more intense in the dorsal compared to ventral part. Contrarily, the staining was more pronounced in the ventral part of the MG. In the AC, the staining was more intense near the surface and diminished toward white matter. We also found that the overall expression level of mGluR2/3 was increased significantly in aged animals in all auditory structures tested. Collectively, our detailed immunostaining findings suggest that the group II mGluRs are widely expressed throughout the central auditory system and their contribution to auditory processing increases with age.
{"title":"Expression of group II mGluRs in the inferior colliculus, medial geniculate body, and auditory cortex increases with age","authors":"Inga Kristaponyte , Nichole L Beebe , Nikhil Harish, Brett R Schofield, Alex V Galazyuk","doi":"10.1016/j.neuroscience.2024.12.021","DOIUrl":"10.1016/j.neuroscience.2024.12.021","url":null,"abstract":"<div><div>Metabotropic glutamate receptors (mGluRs) are widely expressed throughout the central nervous system. They are linked to G-protein coupled receptors and are known to modulate synaptic transmission. The data regarding their expression in auditory structures are not systematic and mainly originate from physiological studies where expression was used to support physiological findings. MGluRs are classified into three groups based on their sequence homology, G protein-coupling, and ligand selectivity. Our recent physiological findings made us focus on the group II mGluRs. The objective of this study was to characterize group II mGluR expression, and whether it changes in aged brains, in three central auditory structures: inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). We performed immunostaining experiments followed by optical density quantification in young and old mice. We found group II mGluR staining in the IC, MG, and AC. However, the intensity of this staining was not uniform within these auditory structures. In the IC expression was more intense in the dorsal compared to ventral part. Contrarily, the staining was more pronounced in the ventral part of the MG. In the AC, the staining was more intense near the surface and diminished toward white matter. We also found that the overall expression level of mGluR2/3 was increased significantly in aged animals in all auditory structures tested. Collectively, our detailed immunostaining findings suggest that the group II mGluRs are widely expressed throughout the central auditory system and their contribution to auditory processing increases with age.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 227-238"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854730","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}
The optimal stimulation frequency for inducing neuromodulatory effects remains unclear. The purpose of our study was to investigate the effect of neuromuscular electrical stimulation (NMES) with different frequencies on cortical and spinal excitability. Thirteen able-bodied individuals participated in the experiment involving NMES: (i) low-frequency at 25 Hz, (ii) high-frequency at 100 Hz, and (iii) mixed-frequency at 25 and 100 Hz switched every one second. All interventions were applied on the tibialis anterior muscle using a 10 sec ON / 10 sec OFF duty cycle for 10 min, using motor-level NMES at 120 % of the individual motor threshold for each stimulating frequency. Assessments were performed at baseline, immediately after, and 30 min after the interventions. Corticospinal excitability and intracortical inhibition were examined using transcranial magnetic stimulation by assessing the motor evoked potentials and cortical silent period, respectively. Spinal motoneuron excitability and neuromuscular propagation were assessed using peripheral nerve stimulation by evaluating F-wave and maximum motor (Mmax) responses, respectively. Maximal voluntary contraction (MVC) was evaluated during isometric dorsiflexion force exertion. Motor performance was also evaluated during the ankle dorsiflexion force-matching task. Our results showed that mixed frequency was most effective in modulating corticospinal excitability, although motor performance was not affected by any intervention. The cortical silent period was prolonged and Mmax was inhibited by all frequencies, while the F-wave and MVC were unaffected. Mixed-frequency stimulation could recruit a more diverse range of motor units, which are recruited in a stimulus frequency-specific manner, than single-frequency stimulation, and thus may have affected corticospinal facilitation.
{"title":"Frequency-dependent corticospinal facilitation following tibialis anterior neuromuscular electrical stimulation","authors":"Shota Tsugaya , Atsushi Sasaki , Suzufumi Arai , Taishin Nomura , Matija Milosevic","doi":"10.1016/j.neuroscience.2024.12.030","DOIUrl":"10.1016/j.neuroscience.2024.12.030","url":null,"abstract":"<div><div>The optimal stimulation frequency for inducing neuromodulatory effects remains unclear. The purpose of our study was to investigate the effect of neuromuscular electrical stimulation (NMES) with different frequencies on cortical and spinal excitability. Thirteen able-bodied individuals participated in the experiment involving NMES: (i) low-frequency at 25 Hz, (ii) high-frequency at 100 Hz, and (iii) mixed-frequency at 25 and 100 Hz switched every one second. All interventions were applied on the tibialis anterior muscle using a 10 sec ON / 10 sec OFF duty cycle for 10 min, using motor-level NMES at 120 % of the individual motor threshold for each stimulating frequency. Assessments were performed at baseline, immediately after, and 30 min after the interventions. Corticospinal excitability and intracortical inhibition were examined using transcranial magnetic stimulation by assessing the motor evoked potentials and cortical silent period, respectively. Spinal motoneuron excitability and neuromuscular propagation were assessed using peripheral nerve stimulation by evaluating F-wave and maximum motor (M<sub>max</sub>) responses, respectively. Maximal voluntary contraction (MVC) was evaluated during isometric dorsiflexion force exertion. Motor performance was also evaluated during the ankle dorsiflexion force-matching task. Our results showed that mixed frequency was most effective in modulating corticospinal excitability, although motor performance was not affected by any intervention. The cortical silent period was prolonged and M<sub>max</sub> was inhibited by all frequencies, while the F-wave and MVC were unaffected. Mixed-frequency stimulation could recruit a more diverse range of motor units, which are recruited in a stimulus frequency-specific manner, than single-frequency stimulation, and thus may have affected corticospinal facilitation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 60-71"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864061","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}
The aim of this study was to assess the potential causal relationship between lifestyle factors and intracranial aneurysms (IAs) using a two-sample Mendelian randomization (MR) approach. The study used a pooled dataset from a genome-wide association study that covered information on 24 lifestyle factors, intracranial aneurysm cases, subarachnoid hemorrhage, and unruptured aneurysms. Five MR methods were applied for analysis by selecting single nucleotide polymorphisms as instrumental variables, with the inverse variance weighting method as the main method. To ensure the stability of the results, horizontal multiple validity tests, sensitivity analyses, and inverse MR were performed, and genetically determined exposure factors were adjusted by multivariate MR. Several lifestyle factors were found to have a significant genetic causal effect on the occurrence and development of intracranial aneurysms. For example, lamb intake, smoking initiation, number of cigarettes smoked per day, length of television viewing, and fatigue were identified as genetic risk factors and strongly associated with aneurysm rupture, whereas red wine intake showed some genetic protection against intracranial aneurysms and similarly affected aneurysm rupture. Sensitivity analyses and inverse MR verified the robustness of these results. After adjusting for exposure factors, multivariate MR confirmed daily smoking and smoking initiation as risk factors for intracranial aneurysms, unruptured aneurysms, and subarachnoid hemorrhage, whereas red wine intake was a genetically protective factor against intracranial aneurysms and subarachnoid hemorrhage. This MR analysis revealed a genetic causal link between specific lifestyle factors and intracranial aneurysms, emphasizing the need for further studies to confirm these findings and explore their mechanisms.
{"title":"Modifiable lifestyle factors and risk of intracranial aneurysm: A univariate and multivariate Mendelian randomisation study","authors":"Jiacong Tan, Huaxin Zhu, Yanyang Zeng, Jiawei Li, Yeyu Zhao, Meihua Li","doi":"10.1016/j.neuroscience.2024.12.034","DOIUrl":"10.1016/j.neuroscience.2024.12.034","url":null,"abstract":"<div><div>The aim of this study was to assess the potential causal relationship between lifestyle factors and intracranial aneurysms (IAs) using a two-sample Mendelian randomization (MR) approach. The study used a pooled dataset from a genome-wide association study that covered information on 24 lifestyle factors, intracranial aneurysm cases, subarachnoid hemorrhage, and unruptured aneurysms. Five MR methods were applied for analysis by selecting single nucleotide polymorphisms as instrumental variables, with the inverse variance weighting method as the main method. To ensure the stability of the results, horizontal multiple validity tests, sensitivity analyses, and inverse MR were performed, and genetically determined exposure factors were adjusted by multivariate MR. Several lifestyle factors were found to have a significant genetic causal effect on the occurrence and development of intracranial aneurysms. For example, lamb intake, smoking initiation, number of cigarettes smoked per day, length of television viewing, and fatigue were identified as genetic risk factors and strongly associated with aneurysm rupture, whereas red wine intake showed some genetic protection against intracranial aneurysms and similarly affected aneurysm rupture. Sensitivity analyses and inverse MR verified the robustness of these results. After adjusting for exposure factors, multivariate MR confirmed daily smoking and smoking initiation as risk factors for intracranial aneurysms, unruptured aneurysms, and subarachnoid hemorrhage, whereas red wine intake was a genetically protective factor against intracranial aneurysms and subarachnoid hemorrhage. This MR analysis revealed a genetic causal link between specific lifestyle factors and intracranial aneurysms, emphasizing the need for further studies to confirm these findings and explore their mechanisms.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 9-16"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872362","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2024.11.019
Xinru Yan, Chunxue Jiang, Ziyao Han, Dishu Huang, Li Cheng, Wei Han, Li Jiang
Myelination is the process by which oligodendrocytes ensheathe axons to form myelin sheaths. Myelination is a crucial aspect of brain development and is closely associated with central nervous system abnormalities. However, previous studies have found that advanced maternal age might affect the myelination of offspring, potentially through the pathway of disrupting DNA methylation levels in the offspring’s hippocampus. Current research has demonstrated that ascorbic acid can promote hydroxymethylation to reduce methylation levels in vivo. This study aims to verify the relationship between ascorbic acid and myelination, as well as the specific mechanism involved. Initially, oligodendrocyte differentiation was observed using immunofluorescence and Western blot. Myelination was assessed through Luxol Fast Blue staining, Glycine silver staining, immunofluorescence, and transmission electron microscopy. The demethylation level of oligodendrocyte progenitor cells was detected by immunofluorescence co-expression of OLIG2 and DNA hydroxylase ten-eleven translocation 1 (TET1), TET2, and TET3. Our study found that advanced maternal age could impair myelination in the hippocampus and corpus callosum of offspring. Ascorbic acid intervention may induce TET1 and TET2-mediated hydroxymethylation to ameliorate myelination disorders, promote myelination and maturation, and reverse the effects of advanced maternal age on offspring.
髓鞘化是少突胶质细胞包裹轴突形成髓鞘的过程。髓鞘化是大脑发育的关键环节,与中枢神经系统异常密切相关。然而,以往的研究发现,高龄产妇可能会影响后代的髓鞘化,其途径可能是破坏后代海马中的 DNA 甲基化水平。目前的研究表明,抗坏血酸可促进羟甲基化,从而降低体内的甲基化水平。本研究旨在验证抗坏血酸与髓鞘化之间的关系及其具体机制。首先,使用免疫荧光和 Western 印迹法观察少突胶质细胞的分化。髓鞘化是通过鲁索快蓝染色、甘氨酸银染色、免疫荧光和透射电子显微镜进行评估的。通过免疫荧光共同表达 OLIG2 和 DNA 羟化酶十-十一转位 1(TET1)、TET2 和 TET3,检测少突胶质祖细胞的去甲基化水平。我们的研究发现,高龄产妇会损害后代海马和胼胝体的髓鞘化。抗坏血酸干预可诱导 TET1 和 TET2 介导的羟甲基化,从而改善髓鞘化障碍,促进髓鞘化和成熟,并逆转高龄产妇对后代的影响。
{"title":"Effects of ascorbic acid on myelination in offspring of advanced maternal age","authors":"Xinru Yan, Chunxue Jiang, Ziyao Han, Dishu Huang, Li Cheng, Wei Han, Li Jiang","doi":"10.1016/j.neuroscience.2024.11.019","DOIUrl":"10.1016/j.neuroscience.2024.11.019","url":null,"abstract":"<div><div>Myelination is the process by which oligodendrocytes ensheathe axons to form myelin sheaths. Myelination is a crucial aspect of brain development and is closely associated with central nervous system abnormalities. However, previous studies have found that advanced maternal age might affect the myelination of offspring, potentially through the pathway of disrupting DNA methylation levels in the offspring’s hippocampus. Current research has demonstrated that ascorbic acid can promote hydroxymethylation to reduce methylation levels in vivo. This study aims to verify the relationship between ascorbic acid and myelination, as well as the specific mechanism involved. Initially, oligodendrocyte differentiation was observed using immunofluorescence and Western blot. Myelination was assessed through Luxol Fast Blue staining, Glycine silver staining, immunofluorescence, and transmission electron microscopy. The demethylation level of oligodendrocyte progenitor cells was detected by immunofluorescence co-expression of OLIG2 and DNA hydroxylase ten-eleven translocation 1 (TET1), TET2, and TET3. Our study found that advanced maternal age could impair myelination in the hippocampus and corpus callosum of offspring. Ascorbic acid intervention may induce TET1 and TET2-mediated hydroxymethylation to ameliorate myelination disorders, promote myelination and maturation, and reverse the effects of advanced maternal age on offspring.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 218-226"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687724","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2024.12.020
Weiping Chen , Zhiping Wu , Zhijuan Cheng , Yangbo Zhang , Qinghua Luo , Min Yin
Background
Microglia polarization plays a crucial role in inflammatory injury of brain following intracerebral hemorrhage (ICH). Heme oxygenase-1 (HO-1) has demonstrated protective properties against inflammation and promote hematoma clearance after ICH. The objective of this study was to explore impacts of HO-1 on microglia polarization and phagocytosis after ICH, along with the underlying mechanism.
Methods
ICH model was constructed in C57BL/6 mice. Neurological deficit of ICH mice was evaluated. HE detected pathological changes of mouse brain tissue. Immunofluorescence staining tested co-localization between HO-1 or NF-κB p65 and IBA1. The expressions of gene and proteins were detected by RT-qPCR and Western blot, respectively. Flow cytometry determined microglial polarization phenotype and neuron apoptosis. Cell viability of neuron was assessed by CCK-8. Red blood cells labeled by PKH-26 and co-cultured with microglia for examining microglial erythrophagocytosis.
Results
Both HO-1 and NF-κB p65 phosphorylation were elevated in brain tissues of ICH mice. ZnPP, a HO-1 inhibitor, could exacerbate microglial M1 polarization and nerve injury, as well as repress microglial erythrophagocytosis in vitro and hematoma clearance in vivo. On the contrary, Tat-NBD, a NF-κB inhibitor, greatly suppressed microglial M1 polarization, and induced M2 polarization and microglial erythrophagocytosis, thus improving nerve injury and hematoma clearance after ICH. Notably, it was observed that NF-κB p65 could be activated by ZnPP treatment, and the regulatory roles of ZnPP on microglial polarization and erythrophagocytosis after ICH in vivo and in vitro were all diminished by Tat-NBD.
Conclusion
Therefore, our data demonstrated that HO-1 alleviated nerve injury and induced M2 polarization and phagocytosis of microglia after ICH via inhibiting NF-κB signaling pathway, which could provide deepen the pathological understanding of ICH and provide potential intervention targets and drug candidate for ICH.
{"title":"HO-1 represses NF-κB signaling pathway to mediate microglia polarization and phagocytosis in intracerebral hemorrhage","authors":"Weiping Chen , Zhiping Wu , Zhijuan Cheng , Yangbo Zhang , Qinghua Luo , Min Yin","doi":"10.1016/j.neuroscience.2024.12.020","DOIUrl":"10.1016/j.neuroscience.2024.12.020","url":null,"abstract":"<div><h3>Background</h3><div>Microglia polarization plays a crucial role in inflammatory injury of brain following intracerebral hemorrhage (ICH). Heme oxygenase-1 (HO-1) has demonstrated protective properties against inflammation and promote hematoma clearance after ICH. The objective of this study was to explore impacts of HO-1 on microglia polarization and phagocytosis after ICH, along with the underlying mechanism.</div></div><div><h3>Methods</h3><div>ICH model was constructed in C57BL/6 mice. Neurological deficit of ICH mice was evaluated. HE detected pathological changes of mouse brain tissue. Immunofluorescence staining tested co-localization between HO-1 or NF-κB p65 and IBA1. The expressions of gene and proteins were detected by RT-qPCR and Western blot, respectively. Flow cytometry determined microglial polarization phenotype and neuron apoptosis. Cell viability of neuron was assessed by CCK-8. Red blood cells labeled by PKH-26 and co-cultured with microglia for examining microglial erythrophagocytosis.</div></div><div><h3>Results</h3><div>Both HO-1 and NF-κB p65 phosphorylation were elevated in brain tissues of ICH mice. ZnPP, a HO-1 inhibitor, could exacerbate microglial M1 polarization and nerve injury, as well as repress microglial erythrophagocytosis in vitro and hematoma clearance in vivo. On the contrary, Tat-NBD, a NF-κB inhibitor, greatly suppressed microglial M1 polarization, and induced M2 polarization and microglial erythrophagocytosis, thus improving nerve injury and hematoma clearance after ICH. Notably, it was observed that NF-κB p65 could be activated by ZnPP treatment, and the regulatory roles of ZnPP on microglial polarization and erythrophagocytosis after ICH in vivo and in vitro were all diminished by Tat-NBD.</div></div><div><h3>Conclusion</h3><div>Therefore, our data demonstrated that HO-1 alleviated nerve injury and induced M2 polarization and phagocytosis of microglia after ICH via inhibiting NF-κB signaling pathway, which could provide deepen the pathological understanding of ICH and provide potential intervention targets and drug candidate for ICH.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 17-27"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822319","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2024.12.032
Vandreza Cardoso Bortolotto , Mustafa Munir Mustafa Dahleh , Luiza Souza Marques , Stífani Machado Araujo Borstmann , Cristini Escobar Viana , Franciane Cabral Pinheiro , Franciéle Romero Machado Balok , Luana Barreto Meichtry , Silvana Peterini Boeira , Gustavo Petri Guerra , Cristina Wayne Nogueira , Marina Prigol
Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex. To induce hypothyroidism, mice were exposed to 0.1 % methimazole (MTZ) in the drinking water for 31 days. After confirming low thyroid hormones levels, the mice received either vehicle or chrysin (20 mg/kg) intragastrically once a day for 28 consecutive days. Memory tests were conducted in two separate experiments (experiment 1: Y-maze and reverse Morris water maze; experiment 2: object recognition task and step-down latency), ensuring no memories overlap. Following the tests, the brain samples were collected to analyses ex vivo. Hypothyroid mice exhibited deficits in cognitive flexibility and various memory types, along with altered protein expression related to the BDNF/TrkB/Creb signaling pathway and increased AKT levels in hippocampus and prefrontal cortex. Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels. Our findings suggest that hypothyroidism impairs cognitive flexibility and memory through the BDNF/TrkB/AKT/Creb pathway, which chrysin modulates, operating as a neuroprotector in hypothyroidism. This research sheds light on the potential therapeutic benefits of chrysin for memory-related issues in hypothyroidism.
{"title":"Chrysin modulates the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway: Acting in the improvement of cognitive flexibility and declarative, working and aversive memory deficits caused by hypothyroidism in C57BL/6 female mice","authors":"Vandreza Cardoso Bortolotto , Mustafa Munir Mustafa Dahleh , Luiza Souza Marques , Stífani Machado Araujo Borstmann , Cristini Escobar Viana , Franciane Cabral Pinheiro , Franciéle Romero Machado Balok , Luana Barreto Meichtry , Silvana Peterini Boeira , Gustavo Petri Guerra , Cristina Wayne Nogueira , Marina Prigol","doi":"10.1016/j.neuroscience.2024.12.032","DOIUrl":"10.1016/j.neuroscience.2024.12.032","url":null,"abstract":"<div><div>Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex. To induce hypothyroidism, mice were exposed to 0.1 % methimazole (MTZ) in the drinking water for 31 days. After confirming low thyroid hormones levels, the mice received either vehicle or chrysin (20 mg/kg) intragastrically once a day for 28 consecutive days. Memory tests were conducted in two separate experiments (experiment 1: Y-maze and reverse Morris water maze; experiment 2: object recognition task and step-down latency), ensuring no memories overlap. Following the tests, the brain samples were collected to analyses <em>ex vivo</em>. Hypothyroid mice exhibited deficits in cognitive flexibility and various memory types, along with altered protein expression related to the BDNF/TrkB/Creb signaling pathway and increased AKT levels in hippocampus and prefrontal cortex. Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels. Our findings suggest that hypothyroidism impairs cognitive flexibility and memory through the BDNF/TrkB/AKT/Creb pathway, which chrysin modulates, operating as a neuroprotector in hypothyroidism. This research sheds light on the potential therapeutic benefits of chrysin for memory-related issues in hypothyroidism.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 28-38"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872169","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2024.12.049
Chen-Lin Gu , Lu Zhang , Yan Zhu , Ting-Yu Bao , Yu-Ting Zhu , Yu-Tong Chen , Han-Qing Pang
Vascular obstruction often causes inadequate oxygen and nutrient supply to the brain. This deficiency results in cerebral ischemic injury, which significantly impairs neurological function. This review aimed to explore the neuroprotective and regenerative effects of nerve growth factor (NGF) in cerebral ischemic injury. NGF, a crucial neurotrophic factor, could inhibit neuronal apoptosis, reduce inflammatory responses, and promote axon regeneration and angiogenesis through its interaction with TrkA, a high-affinity receptor. These functions were closely related to the activation of Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) and Mitogen-Activated Protein Kinase (MAPK) pathways. Moreover, the mechanisms of NGF in the acute and recovery phases, along with the strategies to enhance its therapeutic effects using delivery systems (such as intranasal administration, nanovesicles, and gene therapy) were also summarized. Although NGF shows great potential for clinical application, its delivery efficiency and long-term safety still need more research and improvements. Future research should focus on exploring the specific action mechanism of NGF, optimizing the delivery strategy, and evaluating its long-term efficacy and safety to facilitate its clinical transformation in cerebral ischemic stroke.
{"title":"Exploring the cellular and molecular basis of nerve growth factor in cerebral ischemia recovery","authors":"Chen-Lin Gu , Lu Zhang , Yan Zhu , Ting-Yu Bao , Yu-Ting Zhu , Yu-Tong Chen , Han-Qing Pang","doi":"10.1016/j.neuroscience.2024.12.049","DOIUrl":"10.1016/j.neuroscience.2024.12.049","url":null,"abstract":"<div><div>Vascular obstruction often causes inadequate oxygen and nutrient supply to the brain. This deficiency results in cerebral ischemic injury, which significantly impairs neurological function. This review aimed to explore the neuroprotective and regenerative effects of nerve growth factor (NGF) in cerebral ischemic injury. NGF, a crucial neurotrophic factor, could inhibit neuronal apoptosis, reduce inflammatory responses, and promote axon regeneration and angiogenesis through its interaction with TrkA, a high-affinity receptor. These functions were closely related to the activation of Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) and Mitogen-Activated Protein Kinase (MAPK) pathways. Moreover, the mechanisms of NGF in the acute and recovery phases, along with the strategies to enhance its therapeutic effects using delivery systems (such as intranasal administration, nanovesicles, and gene therapy) were also summarized. Although NGF shows great potential for clinical application, its delivery efficiency and long-term safety still need more research and improvements. Future research should focus on exploring the specific action mechanism of NGF, optimizing the delivery strategy, and evaluating its long-term efficacy and safety to facilitate its clinical transformation in cerebral ischemic stroke.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 190-197"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915061","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2024.12.027
Oliver W.G. Wood , Jason H.Y. Yeung , Thulani H. Palpagama , Clinton Turner , Henry J. Waldvogel , Richard L.M. Faull , Andrea Kwakowsky
Alzheimer’s disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation.
{"title":"Upregulated excitatory amino acid transporter 1 (EAAT1) expression in the human medial temporal lobe in Alzheimer’s disease","authors":"Oliver W.G. Wood , Jason H.Y. Yeung , Thulani H. Palpagama , Clinton Turner , Henry J. Waldvogel , Richard L.M. Faull , Andrea Kwakowsky","doi":"10.1016/j.neuroscience.2024.12.027","DOIUrl":"10.1016/j.neuroscience.2024.12.027","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"566 ","pages":"Pages 87-96"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854776","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2025.02.009
Valters Abolins , Edgars Bernans , Mark L. Latash
We used the framework of the uncontrolled manifold (UCM) hypothesis to explore the origin of inter-trial variance within the UCM, which by definition does not affect the salient performance variable, during accurate two-finger force production. Specifically, we tested several hypotheses on two main sources of variance within the UCM, variability in the sharing patterns between the fingers across trials and covaried variability in finger forces within individual trials. We also explored effects on unintentional changes in the structure of variance during preparation for a quick force change and during force drift without visual feedback. Fourteen young healthy participants performed two-finger force production trials with feedback on total force only or individual finger forces. In one part, they were instructed to produce a quick force pulse in a self-paced manner. In the other, they tried to keep finger forces unchanged without visual feedback. All manipulations led to significant changes in variance along the UCM, but not the ORT, space orthogonal to the UCM. Namely, the relative variance along the UCM dropped prior to quick force production and was not different from the ORT after the force drift. Changing the initial magnitude of variance along the UCM was reflected in its magnitude during anticipatory synergy adjustments prior to the force pulse and following the unintentional force drift. We interpret the results assuming a hierarchical control with two commands, reciprocal and coactivation. The results support the scheme with two contributing factors to variance along the UCM, likely associated with feed-forward and feedback mechanisms.
{"title":"On the origin of variance along the uncontrolled manifold: Its effects on anticipatory and spontaneous changes in performance-stabilizing synergies in force production tasks","authors":"Valters Abolins , Edgars Bernans , Mark L. Latash","doi":"10.1016/j.neuroscience.2025.02.009","DOIUrl":"10.1016/j.neuroscience.2025.02.009","url":null,"abstract":"<div><div>We used the framework of the uncontrolled manifold (UCM) hypothesis to explore the origin of inter-trial variance within the UCM, which by definition does not affect the salient performance variable, during accurate two-finger force production. Specifically, we tested several hypotheses on two main sources of variance within the UCM, variability in the sharing patterns between the fingers across trials and covaried variability in finger forces within individual trials. We also explored effects on unintentional changes in the structure of variance during preparation for a quick force change and during force drift without visual feedback. Fourteen young healthy participants performed two-finger force production trials with feedback on total force only or individual finger forces. In one part, they were instructed to produce a quick force pulse in a self-paced manner. In the other, they tried to keep finger forces unchanged without visual feedback. All manipulations led to significant changes in variance along the UCM, but not the ORT, space orthogonal to the UCM. Namely, the relative variance along the UCM dropped prior to quick force production and was not different from the ORT after the force drift. Changing the initial magnitude of variance along the UCM was reflected in its magnitude during anticipatory synergy adjustments prior to the force pulse and following the unintentional force drift. We interpret the results assuming a hierarchical control with two commands, reciprocal and coactivation. The results support the scheme with two contributing factors to variance along the UCM, likely associated with feed-forward and feedback mechanisms.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 92-102"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372958","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 : 2025-02-06DOI: 10.1016/j.neuroscience.2025.02.012
Zhiqiang Yan , Wenjia Zhang , Qiufeng Dong , Jie Dong , Yingying Huang , Xiaofan Jiang , Hao Yan
Determining the neural bases of basic linguistic composition is central to research on the cognitive neuroscience of language. The left anterior temporal lobe (LATL) is widely reported during linguistic composition of visual stimuli in magnetoencephalography (MEG) studies. However, this effect is less reported during the linguistic composition of auditory stimuli in intracranial electroencephalography (iEEG) studies. To further test this discrepancy, we directly examined the composition effect in LATL by combining the iEEG technique with visual stimuli. Participants were asked to read minimal two-word phrases in the composition condition and read words preceded by pound signs in the noncomposition condition. The results showed that high-gamma power in the LATL was higher in the composition condition compared to the noncomposition condition. These results provide more substantial evidence for the role of LATL in basic linguistic composition (at least in visual modality) and highlight the potential role of stimuli modality (visual vs. auditory) in the phrasal composition effect in LATL.
{"title":"The role of left anterior temporal lobe in basic linguistic composition: Evidence from stereo-electroencephalography","authors":"Zhiqiang Yan , Wenjia Zhang , Qiufeng Dong , Jie Dong , Yingying Huang , Xiaofan Jiang , Hao Yan","doi":"10.1016/j.neuroscience.2025.02.012","DOIUrl":"10.1016/j.neuroscience.2025.02.012","url":null,"abstract":"<div><div>Determining the neural bases of basic linguistic composition is central to research on the cognitive neuroscience of language. The left anterior temporal lobe (LATL) is widely reported during linguistic composition of visual stimuli in magnetoencephalography (MEG) studies. However, this effect is less reported during the linguistic composition of auditory stimuli in intracranial electroencephalography (iEEG) studies. To further test this discrepancy, we directly examined the composition effect in LATL by combining the iEEG technique with visual stimuli. Participants were asked to read minimal two-word phrases in the composition condition and read words preceded by pound signs in the noncomposition condition. The results showed that high-gamma power in the LATL was higher in the composition condition compared to the noncomposition condition. These results provide more substantial evidence for the role of LATL in basic linguistic composition (at least in visual modality) and highlight the potential role of stimuli modality (visual vs. auditory) in the phrasal composition effect in LATL.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 155-160"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373938","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}