Pub Date : 2024-04-24DOI: 10.1016/j.jchemneu.2024.102424
Lili Ma , Na Mi , Zhi Wang , Rui Bao , Jing Fang , Yajing Ren , Xiuzhi Xu , Hongjia Zhang , Ying Tang
Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells in vitro. IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway in vivo and in vitro, respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models in vivo and in vitro by the AMPK/mTOR signaling pathway.
{"title":"Knockdown of IRF8 alleviates neuroinflammation through regulating microglial activation in Parkinson’s disease","authors":"Lili Ma , Na Mi , Zhi Wang , Rui Bao , Jing Fang , Yajing Ren , Xiuzhi Xu , Hongjia Zhang , Ying Tang","doi":"10.1016/j.jchemneu.2024.102424","DOIUrl":"10.1016/j.jchemneu.2024.102424","url":null,"abstract":"<div><p>Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells <em>in vitro</em>. IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway <em>in vivo</em> and <em>in vitro</em>, respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models <em>in vivo</em> and <em>in vitro</em> by the AMPK/mTOR signaling pathway.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102424"},"PeriodicalIF":2.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1016/j.jchemneu.2024.102422
Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot
L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu2/3 activation, we performed autoradiographic binding with [3H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [3H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, P<0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (49 % vs sham-lesioned rats, P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, P<0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05), GP (34 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [3H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all P<0.05). These results suggest that alterations in mGlu2/3 receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.
L-3,4-二羟基苯丙氨酸(L-DOPA)是治疗帕金森病(PD)运动症状的首选药物,但其长期使用受到运动障碍等并发症的阻碍。临床前研究发现,激活代谢型谷氨酸 2 型和 3 型(mGlu2/3)受体可减轻 L-DOPA 引起的运动障碍。为了深入了解激活 mGlu2/3 受体抗运动障碍的机理,我们在经 L-DOPA 治疗的 6-羟基多巴胺(6-OHDA)缺失大鼠出现轻度或重度运动障碍的脑切片中,以及未经 L-DOPA 治疗的 6-OHDA 缺失动物和假缺失动物的脑切片中,用[3H]-LY-341,495 进行了自显影结合。在同侧大脑半球,轻度运动障碍的 6-OHDA 失神经节大鼠显示,在内侧脑核(EPN,30% vs 假失神经节大鼠,P<0.05)、苍白球(GP,28% vs 假失神经节大鼠,P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001)和初级运动皮层(49 % vs 假缺损大鼠,P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001)。严重运动障碍的 6-OHDA 失神经节大鼠表现出初级运动皮层结合力增加(43% vs 轻度运动障碍的 6-OHDA 失神经节大鼠,P<0.05)。在对侧半球,轻度运动障碍的 6-OHDA 病变大鼠在 EPN(30 % vs 假缺损大鼠;24 % vs L-DOPA 未处理的 6-OHDA 病变大鼠,均为 P<0.05)、GP(34 % vs L-DOPA 未处理的 6-OHDA 病变大鼠,均为 P<0.0505)、GP(34 % vs 假缺失大鼠,P<0.05;23 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠,P<0.001)和初级运动皮层(50 % vs 假缺失大鼠;44 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠,均为 P<0.05)。严重运动障碍的 6-OHDA 病变大鼠 GP 结合力下降(30% vs 假缺失大鼠;19% vs L-DOPA 未治疗的 6-OHDA 病变大鼠,均为 P<0.05)。6-OHDA缺失动物的异常不自主运动评分与同侧纹状体、同侧EPN、同侧初级运动皮层和对侧初级运动皮层中的[3H]-LY-341,495结合呈正相关(均为P<0.05)。这些结果表明,mGlu2/3 受体水平的改变可能是缓解运动障碍的内源性代偿机制的一部分。
{"title":"Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain","authors":"Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot","doi":"10.1016/j.jchemneu.2024.102422","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102422","url":null,"abstract":"<div><p>L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu<sub>2/3</sub>) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu<sub>2/3</sub> activation, we performed autoradiographic binding with [<sup>3</sup>H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [<sup>3</sup>H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, <em>P</em><0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (49 % vs sham-lesioned rats, <em>P</em><0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, <em>P</em><0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05), GP (34 % vs sham-lesioned rats, <em>P</em><0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em><0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em><0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [<sup>3</sup>H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all <em>P</em><0.05). These results suggest that alterations in mGlu<sub>2/3</sub> receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102422"},"PeriodicalIF":2.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061824000358/pdfft?md5=ec2ef69433d73816b2c7b2d6f385eb7d&pid=1-s2.0-S0891061824000358-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20DOI: 10.1016/j.jchemneu.2024.102421
Mujittapha U. Sirajo , Yahya K. Maigari , Abdulrashid Sunusi , Adam N. Jibril , Isa Usman Lawal , Badamasi M. Ibrahim
Background
Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear.
Methods
Twenty-four adult mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize reactive astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections.
Results
The EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D&A resulted in significant reductions in IL-6 levels. Only the Vitamin D&A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D&A groups. IL-4 was notably increased in the Vitamin D&A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, and vitamin D&A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other groups.
Conclusions
EPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to suppres pro-inflammatory cytokines and repress anti-inflammatory cytokines associated with astrocyte activation.
背景锥体外系综合征(EPS)是抗精神病药物对神经系统的副作用,以运动障碍为特征。方法将 24 只成年小鼠分为四组:阳性对照组和阴性对照组,一组接受多巴胺拮抗剂治疗,另一组同时接受多巴胺拮抗剂和维生素 D 和 A 治疗。制备皮质基底环的切片,特别是运动皮层(M1)和基底核(CPu),用于免疫组织化学(IHC),并用胶质纤维酸性蛋白(GFAP)染色以观察反应性星形胶质细胞。结果 EPS组M1和CPu中的TNF-α和IL-6水平显著升高。使用多巴胺激动剂和维生素 D&A 治疗后,IL-6 水平显著降低。只有维生素D&A组的TNF-α水平明显下降。EPS组的IL-4和IL-13显著下降,多巴胺激动剂组和维生素D&A组的IL-13显著升高。IL-4 在维生素 D&A 组明显升高。EPS 组的多巴胺浓度明显下降,而接受多巴胺激动剂和维生素 D&A 治疗的各组情况有所改善。结论EPS与星形胶质细胞的活化、促炎细胞因子的激增、抗炎细胞因子的减少以及皮质基底环路中的多巴胺有关。服用维生素 D3 和维生素 A 可抑制促炎细胞因子,抑制与星形胶质细胞活化相关的抗炎细胞因子。
{"title":"Synergistic action of vitamin D3 and A on motor activity regulation in mice model of extrapyramidal syndrome: Correlational insights into astrocyte regulation, cytokine modulation, and dopaminergic activity","authors":"Mujittapha U. Sirajo , Yahya K. Maigari , Abdulrashid Sunusi , Adam N. Jibril , Isa Usman Lawal , Badamasi M. Ibrahim","doi":"10.1016/j.jchemneu.2024.102421","DOIUrl":"10.1016/j.jchemneu.2024.102421","url":null,"abstract":"<div><h3>Background</h3><p>Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear.</p></div><div><h3>Methods</h3><p>Twenty-four adult mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize reactive astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections.</p></div><div><h3>Results</h3><p>The EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D&A resulted in significant reductions in IL-6 levels. Only the Vitamin D&A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D&A groups. IL-4 was notably increased in the Vitamin D&A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, and vitamin D&A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other groups.</p></div><div><h3>Conclusions</h3><p>EPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to suppres pro-inflammatory cytokines and repress anti-inflammatory cytokines associated with astrocyte activation.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102421"},"PeriodicalIF":2.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1016/j.jchemneu.2024.102420
Jing-Yi Li , Cheng-Mei Zhou , Rui-Lin Jin , Jia-Hui Song , Ke-Chao Yang , Shu-Lei Li , Bai-Hong Tan , Yan-Chao Li
Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.
{"title":"The detection methods currently available for protein aggregation in neurological diseases","authors":"Jing-Yi Li , Cheng-Mei Zhou , Rui-Lin Jin , Jia-Hui Song , Ke-Chao Yang , Shu-Lei Li , Bai-Hong Tan , Yan-Chao Li","doi":"10.1016/j.jchemneu.2024.102420","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102420","url":null,"abstract":"<div><p>Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation <em>in situ</em> under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102420"},"PeriodicalIF":2.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-15DOI: 10.1016/j.jchemneu.2024.102418
Adam Talwalkar , Gage Haden , Kelli A. Duncan
Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. From minutes to months following damage, injury can result in a complex pathophysiology that can lead to temporary or permanent deficits including an array of neurodegenerative symptoms. These changes can include behavioral dysregulation, memory dysfunctions, and mood changes including depression. The nature and severity of impairments resulting from TBIs vary widely given the range of injury type, location, and extent of brain tissue involved. In response to the injury, the brain induces structural and functional changes to promote repair and minimize injury size. Despite its high prevalence, effective treatment strategies for TBI are limited. PNNs are part of the neuronal extracellular matrix (ECM) that mediate synaptic stabilization in the adult brain and thus neuroplasticity. They are associated mostly with inhibitory GABAergic interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance of the brain. The major structural components of PNNs include multiple chondroitin sulfate proteoglycans (CSPGs) as well as other structural proteins. Here we examine the effects of injury on CSPG expression, specifically around the changes in the side change moieties. To investigate CSPG expression following injury, adult male and female zebra finches received either a bilateral penetrating, or no injury and qPCR analysis and immunohistochemistry for components of the CSPGs were examined at 1- or 7-days post-injury. Next, to determine if CSPGs and thus PNNs should be a target for therapeutic intervention, CSPG side chains were degraded at the time of injury with chondroitinase ABC (ChABC) CSPGs moieties were examined. Additionally, GABA receptor mRNA and aromatase mRNA expression was quantified following CSPG degradation as they have been implicated in neuronal survival and neurogenesis. Our data indicate the CSPG moieties change following injury, potentially allowing for a brief period of synaptic reorganization, and that treatments that target CSPG side chains are successful in further targeting this brief critical period by decreasing GABA mRNA receptor expression, but also decreasing aromatase expression.
{"title":"Chondroitin sulfate proteoglycans mRNA expression and degradation in the zebra finch following traumatic brain injury","authors":"Adam Talwalkar , Gage Haden , Kelli A. Duncan","doi":"10.1016/j.jchemneu.2024.102418","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102418","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. From minutes to months following damage, injury can result in a complex pathophysiology that can lead to temporary or permanent deficits including an array of neurodegenerative symptoms. These changes can include behavioral dysregulation, memory dysfunctions, and mood changes including depression. The nature and severity of impairments resulting from TBIs vary widely given the range of injury type, location, and extent of brain tissue involved. In response to the injury, the brain induces structural and functional changes to promote repair and minimize injury size. Despite its high prevalence, effective treatment strategies for TBI are limited. PNNs are part of the neuronal extracellular matrix (ECM) that mediate synaptic stabilization in the adult brain and thus neuroplasticity. They are associated mostly with inhibitory GABAergic interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance of the brain. The major structural components of PNNs include multiple chondroitin sulfate proteoglycans (CSPGs) as well as other structural proteins. Here we examine the effects of injury on CSPG expression, specifically around the changes in the side change moieties. To investigate CSPG expression following injury, adult male and female zebra finches received either a bilateral penetrating, or no injury and qPCR analysis and immunohistochemistry for components of the CSPGs were examined at 1- or 7-days post-injury. Next, to determine if CSPGs and thus PNNs should be a target for therapeutic intervention, CSPG side chains were degraded at the time of injury with chondroitinase ABC (ChABC) CSPGs moieties were examined. Additionally, GABA receptor mRNA and aromatase mRNA expression was quantified following CSPG degradation as they have been implicated in neuronal survival and neurogenesis. Our data indicate the CSPG moieties change following injury, potentially allowing for a brief period of synaptic reorganization, and that treatments that target CSPG side chains are successful in further targeting this brief critical period by decreasing GABA mRNA receptor expression, but also decreasing aromatase expression.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102418"},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.
亨廷顿氏病(Huntington's disease,HD)是一种遗传性疾病,其特征是纹状体中的神经细胞逐渐退化。最近的科学调查显示,细胞外囊泡(EVs)具有缓解炎症和增强运动功能的治疗潜力。本研究的目的是研究在HD大鼠模型中施用从人脐带血(HUCB)中提取的EVs对其运动能力和炎症水平的影响。通过超速离心从人脐带血中制备EVs以确定所获内容物的性质,然后用DLS和透射电子显微镜(TEM)研究了CD标志物81和9的表达、平均大小及其颗粒的形态。然后,为了诱导 HD 模型,向大鼠腹腔注射 3-硝基丙酸(3-NP)神经毒素,经 HUCB-EVs 处理后,对大鼠进行转体、肌电图(EMG)和空场试验。最后,大鼠被处死并取出纹状体后,进行了苏木精和伊红染色(H&E)、体视学、免疫组化、抗氧化测试和免疫印迹。结果表明,HUCB-EVs 的内容物表达 CD9 和 CD81 标记,并呈球形。此外,注射 HUCB-EVs 还能改善运动和神经肌肉功能,减少神经胶质增生,增加抗氧化活性和炎症因子,并能部分防止神经元的减少。研究结果总体表明,HUCB-EVs 具有神经保护作用,并能减轻 3-NP 毒性作用对神经的炎症反应,有利于 HD 的康复。
{"title":"Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease","authors":"Reza Bahar , Shahram Darabi , Mohsen Norouzian , Susan Roustaei , Shayesteh Torkamani-dordshaikh , Maral Hasanzadeh , Kimia Vakili , Mobina Fathi , Fariba Khodagholi , Neda Kaveh , Shima Jahanbaz , Meysam Hassani Moghaddam , Hojjat-Allah Abbaszadeh , Abbas Aliaghaei","doi":"10.1016/j.jchemneu.2024.102419","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102419","url":null,"abstract":"<div><p>Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"138 ","pages":"Article 102419"},"PeriodicalIF":2.8,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1016/j.jchemneu.2024.102417
Juan Hong , Peidong Dai , Huazheng Liang , Guangbin Sun , Weidong Qi , Yong Bi
Objective
The distribution and role of NMDA receptors is unclear in the afferent signaling complex of the cochlea. The present study aimed to examine the distribution of NMDA receptors in cochlear afferent signaling complex of the adult mouse, and their relationship with ribbon synapses of inner hair cells (IHCs) and GABAergic efferent terminals of the lateral olivocochlear (LOC).
Methods
Immunofluorescence staining in combination with confocal microscopy was used to investigate the distribution of glutamatergic NMDA and AMPA receptors in afferent terminals of SGNs, and their relationship with ribbon synapses of IHCs and GABAergic efferent terminals of LOC.
Results
Terminals with AMPA receptors along with Ribbons of IHC formed afferent synapses in the basal pole of IHCs, and those with NMDA receptors were mainly distributed longitudinally in the IHCs nuclei region. Significant difference was found in the distribution of NMDA and AMPA receptors in IHC afferent signaling complex (P<0.05). Some GABAergic terminals colocalized with NMDA receptors at the IHC nucleus region (P>0.05).
Conclusion
There is significant difference in the distribution of NMDA and AMPA receptors in cochlear afferent signaling complex. NMDA receptors are present in the extra-synaptic region of ribbon synapses of IHCs, and they are related to GABA efferent terminals of the afferent signaling complex.
{"title":"Extrasynaptic distribution of NMDA receptors in cochlear inner hair cell afferent signaling complex","authors":"Juan Hong , Peidong Dai , Huazheng Liang , Guangbin Sun , Weidong Qi , Yong Bi","doi":"10.1016/j.jchemneu.2024.102417","DOIUrl":"10.1016/j.jchemneu.2024.102417","url":null,"abstract":"<div><h3>Objective</h3><p>The distribution and role of NMDA receptors is unclear in the afferent signaling complex of the cochlea. The present study aimed to examine the distribution of NMDA receptors in cochlear afferent signaling complex of the adult mouse, and their relationship with ribbon synapses of inner hair cells (IHCs) and GABAergic efferent terminals of the lateral olivocochlear (LOC).</p></div><div><h3>Methods</h3><p>Immunofluorescence staining in combination with confocal microscopy was used to investigate the distribution of glutamatergic NMDA and AMPA receptors in afferent terminals of SGNs, and their relationship with ribbon synapses of IHCs and GABAergic efferent terminals of LOC.</p></div><div><h3>Results</h3><p>Terminals with AMPA receptors along with Ribbons of IHC formed afferent synapses in the basal pole of IHCs, and those with NMDA receptors were mainly distributed longitudinally in the IHCs nuclei region. Significant difference was found in the distribution of NMDA and AMPA receptors in IHC afferent signaling complex (P<0.05). Some GABAergic terminals colocalized with NMDA receptors at the IHC nucleus region (P>0.05).</p></div><div><h3>Conclusion</h3><p>There is significant difference in the distribution of NMDA and AMPA receptors in cochlear afferent signaling complex. NMDA receptors are present in the extra-synaptic region of ribbon synapses of IHCs, and they are related to GABA efferent terminals of the afferent signaling complex.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102417"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140356764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1016/j.jchemneu.2024.102394
Goran Šimić , Gail M. Rodney
{"title":"Celebrating 37 years of dedication: Reflections on the past and looking toward the future","authors":"Goran Šimić , Gail M. Rodney","doi":"10.1016/j.jchemneu.2024.102394","DOIUrl":"10.1016/j.jchemneu.2024.102394","url":null,"abstract":"","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102394"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061824000073/pdfft?md5=c6f295d27ab40f5218d996a246fdcbd4&pid=1-s2.0-S0891061824000073-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139523282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1016/j.jchemneu.2024.102415
Gabriel S. Rocha , Marco Aurelio M. Freire , Karina M. Paiva , Rodrigo F. Oliveira , Paulo Leonardo A.G. Morais , José Ronaldo Santos , José Rodolfo L.P. Cavalcanti
Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.
{"title":"The neurobiological effects of senescence on dopaminergic system: A comprehensive review","authors":"Gabriel S. Rocha , Marco Aurelio M. Freire , Karina M. Paiva , Rodrigo F. Oliveira , Paulo Leonardo A.G. Morais , José Ronaldo Santos , José Rodolfo L.P. Cavalcanti","doi":"10.1016/j.jchemneu.2024.102415","DOIUrl":"10.1016/j.jchemneu.2024.102415","url":null,"abstract":"<div><p>Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102415"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14DOI: 10.1016/j.jchemneu.2024.102413
Mei-chen Liu , Qing-fa Guo , Wei-wei Zhang , Hong-liang Luo , Wen-jun Zhang , Hai-jun Hu
Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients’ quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.
{"title":"Olfactory ensheathing cells as candidate cells for chronic pain treatment","authors":"Mei-chen Liu , Qing-fa Guo , Wei-wei Zhang , Hong-liang Luo , Wen-jun Zhang , Hai-jun Hu","doi":"10.1016/j.jchemneu.2024.102413","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102413","url":null,"abstract":"<div><p>Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients’ quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102413"},"PeriodicalIF":2.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}