Neurodegenerative Diseases最新文献

{"title":"Prefrontal Cortex Transcriptomic Deconvolution Implicates Monocyte Infiltration in Parkinson's Disease.","authors":"Sai Batchu","doi":"10.1159/000510218","DOIUrl":"https://doi.org/10.1159/000510218","url":null,"abstract":"<p><strong>Introduction: </strong>Although not considered a primary cause, neuroinflammation is associated with many neurodegenerative disorders, including Parkinson's disease (PD).</p><p><strong>Methods: </strong>To elucidate potential immune involvement in PD, the present study imputed immune cell abundances from bulk RNA-sequencing transcriptomic data of PD postmortem prefrontal cortices. CIBERSORTx, an RNA deconvolution algorithm that implements support vector regression, was used to measure the relative abundances of immune cells from a previously published gene expression dataset. Through this machine-learning approach, relative proportions of 22 immune cell subtypes present in the original brain tissue were estimated.</p><p><strong>Results: </strong>Prefrontal cortices from PD patients exhibited significantly higher relative abundances of monocytes compared to neuropathologically normal controls (p value = 0.0005). The relative proportions of the other 21 immune subtypes showed no significant differences between control and PD samples.</p><p><strong>Conclusion and discussion: </strong>The findings corroborate previous reports and suggest monocytes may be involved in PD pathogenesis.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"110-112"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38426969","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}

{"title":"Sleep-Disordered Breathing in Patients with Motor Neurone Disease: One Size Does Not Fit all.","authors":"Vinod Aiyappan,&nbsp;Peter Catcheside,&nbsp;Nick Antic,&nbsp;Graham Keighley-James,&nbsp;Jeremy Mercer,&nbsp;R Doug McEvoy","doi":"10.1159/000513887","DOIUrl":"https://doi.org/10.1159/000513887","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep-disordered breathing (SDB) in patients with motor neurone disease (MND) is normally attributed to hypoventilation due to muscle weakness. However, we have observed different patterns of SDB among MND patients referred for non-invasive ventilation, which do not appear to be explained by respiratory muscle weakness alone.</p><p><strong>Aim: </strong>The aim of this study was to examine the characteristics of SDB in MND.</p><p><strong>Methods: </strong>This is a retrospective analysis of sleep studies (using polysomnography [PSG]), pulmonary function tests, and arterial blood gases in MND patients referred to a tertiary sleep medicine service for clinical review. Sleep apnoeas were characterised as obstructive or central, and to further characterise the nature of SDB, hypopnoeas were classified as obstructive versus central.</p><p><strong>Results: </strong>Among 13 MND patients who had a diagnostic PSG, the mean ± SD age was 68.9 ± 9.8 years, BMI 23.0 ± 4.3 kg/m2, forced vital capacity 55.7 ± 20.9% predicted, and partial pressure of CO2 (arterial blood) 52.7 ± 12.1 mm Hg. A total of 38% of patients (5/13) showed evidence of sleep hypoventilation. The total apnoea/hypopnoea index (AHI) was (median [interquartile range]) 44.4(36.2-56.4)/h, with 92% (12/13) showing an AHI >10/h, predominantly due to obstructive events, although 8% (1/13) also showed frequent central apnoea/hypopnoeas.</p><p><strong>Conclusions: </strong>Patients with MND exhibit a wide variety of SDB. The prevalence of obstructive sleep apnoea (OSA) is surprising considering the normal BMI in most patients. A dystonic tongue and increased upper-airway collapsibility might predispose these patients to OSA. The wide variety of SDB demonstrated might have implications for ventilator settings and patients' outcomes.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 4","pages":"131-138"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25491800","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}

{"title":"Postoperative Cognitive Dysfunction and the Protective Effects of Enriched Environment: A Systematic Review.","authors":"Momin Hua,&nbsp;Jia Min","doi":"10.1159/000513196","DOIUrl":"https://doi.org/10.1159/000513196","url":null,"abstract":"<p><strong>Background: </strong>Currently, the number of individuals who undergo surgery is greatly increased. As a consequence, postoperative cognitive dysfunction (POCD) has gradually gained more attention.</p><p><strong>Summary: </strong>POCD is a perioperative complication requiring sensitive preoperative and postoperative neuropsychiatric tests, and its incidence in both cardiac and noncardiac surgery is high, especially in elderly individuals. Surgical, patient, and anesthetic factors may all lead to the occurrence and development of POCD. The key mechanism of POCD may be the inflammatory response of the central nervous system during surgery, which is similar to that of Alzheimer's disease (AD). Enriched environment (EE), a factor that can significantly improve and prevent neurodegenerative diseases, may have a beneficial effect on POCD. Key Messages: This review aims to elucidate the mechanism of the occurrence and development of POCD, analyze the possible influence of EE on POCD at the molecular level, and provide a direction for its treatment.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 4","pages":"113-122"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25380848","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}

{"title":"Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy.","authors":"Aidana Massalimova,&nbsp;Ruiqing Ni,&nbsp;Roger M Nitsch,&nbsp;Marco Reisert,&nbsp;Dominik von Elverfeldt,&nbsp;Jan Klohs","doi":"10.1159/000515754","DOIUrl":"https://doi.org/10.1159/000515754","url":null,"abstract":"<p><strong>Introduction: </strong>Increased expression of hyperphosphorylated tau and the formation of neurofibrillary tangles are associated with neuronal loss and white matter damage. Using high-resolution ex vivo diffusion tensor imaging (DTI), we investigated microstructural changes in the white and grey matter in the P301L mouse model of human tauopathy at 8.5 months of age. For unbiased computational analysis, we implemented a pipeline for voxel-based analysis (VBA) and atlas-based analysis (ABA) of DTI mouse brain data.</p><p><strong>Methods: </strong>Hemizygous and homozygous transgenic P301L mice and non-transgenic littermates were used. DTI data were acquired for generation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) maps. VBA on the entire brain was performed using SPM8 and the SPM Mouse toolbox. Initially, all DTI maps were coregistered with the Allen mouse brain atlas to bring them to one common coordinate space. In VBA, coregistered DTI maps were normalized and smoothed in order to perform two-sample and unpaired t tests with false discovery rate correction to compare hemizygotes with non-transgenic littermates, homozygotes with non-transgenic littermates, and hemizygotes with homozygotes on each DTI parameter map. In ABA, the average values for selected regions of interests were computed with coregistered DTI maps and labels in Allen mouse brain atlas. Afterwards, a Kruskal-Wallis one-way ANOVA on ranks with a Tukey post hoc test was executed on the estimated average values.</p><p><strong>Results: </strong>With VBA, we found pronounced and brain-wide spread changes when comparing homozygous, P301L mice with non-transgenic littermates, which were not seen when comparing hemizygous P301L with non-transgenic animals. Statistical comparison of DTI metrics in selected brain regions by ABA corroborated findings from VBA. FA was found to be decreased in most brain regions, while MD, RD, and AD were increased in homozygotes compared to hemizygotes and non-transgenic littermates.</p><p><strong>Discussion/conclusion: </strong>High-resolution ex vivo DTI demonstrated brain-wide microstructural and gene-dose-dependent changes in the P301L mouse model of human tauopathy. The DTI analysis pipeline may serve for the phenotyping of models of tauopathy and other brain diseases.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"173-184"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000515754","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38901345","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}

{"title":"The Effects of 8-Week Combined Exercise Training on Inflammatory Markers in Women with Multiple Sclerosis.","authors":"Fahime Tadayon Zadeh,&nbsp;Hamid Amini,&nbsp;Saeed Habibi,&nbsp;Valiallah Shahedi,&nbsp;Amin Isanejad,&nbsp;Mohsen Akbarpour","doi":"10.1159/000518580","DOIUrl":"https://doi.org/10.1159/000518580","url":null,"abstract":"<p><strong>Purpose: </strong>The present study was designed to investigate the effects of 8-week combined endurance, resistance, and balance exercise training on IL-6, CRP, and IL-10 concentrations in women with multiple sclerosis.</p><p><strong>Methods: </strong>Thirty participants with multiple sclerosis (Expanded Disability Status Scale ≤6) were randomized into either an exercise and control groups. The exercise group performed 8-weeks of endurance, resistance, and balance exercise training. Serum concentrations of IL-6, CRP, and IL-10 were measured before and after the 8-week intervention. Moreover, anthropometric measures were determined at the onset of and after the intervention. For within- and between groups comparisons of all variables, t test (independent and dependent) was used (p < 0.05).</p><p><strong>Results: </strong>The results revealed that IL-6 and CRP levels significantly decreased after exercise training (from 6.8 ± 1.52 to 3.2 ± 0.96, p < 0.001 and from 2.76 ± 0.98 to 1.55 ± 0.44, p = <0.001; respectively). Also, exercise training significantly increased IL-10 in the exercise group (from 16.4 ± 2.74 to 23.2 ± 2.11, p < 0.001). There was a significant difference between the 2 groups in all markers in the after 8-week exercise (p < 0.05).</p><p><strong>Conclusions: </strong>One of the characteristics of MS disease is inflammation. Exercise training through physiological mechanisms and without aggravating the inflammatory pathology can be effective in functional and symptom reduction of patients with MS. In confirmation of this, the present study showed that 8 weeks of combined exercise training decreased pro-inflammatory markers (IL-6 and CRP) and increased anti-inflammatory cytokine (IL-10). Our findings suggested that an exercise training program can be an effective strategy for managing the immune system of women with MS at least by its significant effect on inflammatory markers.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"212-216"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000518580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39274498","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}

{"title":"Contents Vol. 20, 2020","authors":"","doi":"10.1159/000519819","DOIUrl":"https://doi.org/10.1159/000519819","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"1 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65298483","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}

{"title":"Elevated Levels of Homocysteinesulfinic Acid in the Plasma of Patients with Amyotrophic Lateral Sclerosis: A Potential Source of Excitotoxicity?","authors":"Aven Lee,&nbsp;Buddhika Jayakody Arachchige,&nbsp;Robert Henderson,&nbsp;James Aylward,&nbsp;Pamela Ann McCombe","doi":"10.1159/000517964","DOIUrl":"https://doi.org/10.1159/000517964","url":null,"abstract":"<p><strong>Objectives: </strong>Excitotoxicity is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). One possible source of excitotoxicity is the presence of sulphur amino acids (SAAs). In the brain of subjects with ALS, there are increased levels of taurine. In the metabolism of methionine to taurine, excitatory sulphur amino acids (SAAs) are formed. These could potentially contribute to excitotoxicity in ALS. The present study has examined whether plasma levels of SAAs in 38 ALS patients differ from those of 30 healthy controls.</p><p><strong>Methods: </strong>Plasma levels of SAAs were measured by liquid chromatography mass spectrometry.</p><p><strong>Results: </strong>There were no significant changes in plasma cysteic acid, cysteine sulfinic acid, and homocysteic acid in ALS patients compared to healthy subjects. Significant elevations in plasma homocysteinesulfinic acid (HCSA) levels (p < 0.0001) were observed in the ALS patients (75.91 ± 15.38 nM) compared to healthy controls (54.06 ± 8.503 nM); 50% of the ALS patients had HCSA levels that were 1.5-2-folds higher than those of controls. Plasma levels of HCSA differed significantly (p = 0.0440) between patients with bulbar onset and spinal onset (68.57 ± 14.20 vs. 79.30 ± 14.95 nM, respectively).</p><p><strong>Conclusion: </strong>HCSA is elevated in the blood of subjects with ALS. Since HCSA can be transported from the blood to the CNS by active transport, has neurotransmitter properties, and can activate synaptic receptors including NMDAR and metabotropic glutamate receptor, it is possible that increases in HCSA could influence glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"200-206"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275602","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}

{"title":"Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington's Disease: A Pilot Study.","authors":"Beatrice Heim,&nbsp;Dora Valent,&nbsp;Federico Carbone,&nbsp;Sabine Spielberger,&nbsp;Florian Krismer,&nbsp;Atbin Djamshidian-Tehrani,&nbsp;Klaus Seppi","doi":"10.1159/000518136","DOIUrl":"https://doi.org/10.1159/000518136","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this pilot study was to investigate change of olfactory functions in Huntington's disease (HD).</p><p><strong>Background: </strong>HD is a neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities. There are several studies reporting olfactory dysfunction in manifest and some studies in premanifest HD carriers, and a recent neuropathological study demonstrated HD-specific protein aggregation in the anterior olfactory nucleus in HD patients. In this study, we wanted to assess olfactory functions as a possible early nonmotor symptom of HD mutation carriers without disease-specific motor symptoms and HD patients.</p><p><strong>Methods: </strong>All participants had genetic confirmed HD and were prospectively recruited during their routine control in a specialized outpatient clinic of the Medical University of Innsbruck, Department of Neurology, Austria. Healthy controls (HCs) were caregivers from patients. They were only included if they were younger than 70 years, scored more than 24/30 points on the Mini Mental State Examination, and had no other disease compromising olfactory function. Furthermore, all participants were tested on the Sniffin' sticks 16-items identification test.</p><p><strong>Results: </strong>We included 23 patients with manifest HD, 13 HD mutation carriers, and 19 HCs. Mutation carriers showed significant impaired odor identification compared to HCs (p < 0.001), as well as Huntington's patients compared with both mutation carriers (p = 0.003) and HCs (p < 0.001).</p><p><strong>Conclusions: </strong>The results of this pilot study suggest that olfactory dysfunction may be an early nonmotor symptom of HD and could be a potential marker to assess disease progression.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"207-211"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000518136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275192","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}

{"title":"Alpha-Synuclein: The Interplay of Pathology, Neuroinflammation, and Environmental Factors in Parkinson's Disease.","authors":"Songzhe He,&nbsp;Shan Zhong,&nbsp;Gang Liu,&nbsp;Jun Yang","doi":"10.1159/000511083","DOIUrl":"https://doi.org/10.1159/000511083","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disease. α-Synuclein (α-syn), which is the main protein component of Lewy bodies, plays an important role in the pathological hallmarks of PD. However, the pathological function of α-syn and the molecular mechanisms responsible for the degeneration of dopaminergic neurons are still elusive.</p><p><strong>Summary: </strong>Cumulative evidence implicates that abnormal processing of α-syn will be predicted to lead to pathological changes in PD. Key Messages: In this review, we summarize the structure and physiological function of α-syn, and further discuss the interplay of pathology, neuroinflammation, and environmental factors in PD. Additionally, we suggest future directions for understanding the toxicity of α-syn to neurons, which may ultimately encourage us to better design disease-modifying therapeutic strategies for PD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"55-64"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38835181","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}

{"title":"Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases.","authors":"Juepu Zhou,&nbsp;Yao Jin,&nbsp;Yuhong Lei,&nbsp;Tianyi Liu,&nbsp;Zheng Wan,&nbsp;Hao Meng,&nbsp;Honglei Wang","doi":"10.1159/000510083","DOIUrl":"https://doi.org/10.1159/000510083","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases.</p><p><strong>Summary: </strong>In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 1","pages":"20-34"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38278668","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}