scholarly journals Different post-mortem brain regions from three Chinese FFI patients induce different reactive profiles both in the first and second generation RT-QuIC assays

Prion ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 163-169
Author(s):  
Kang Xiao ◽  
Qi Shi ◽  
Wei Zhou ◽  
Xiao-Ping Dong
Keyword(s):  
Second Generation ◽  
Brain Regions ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
First And Second Generation

scholarly journals Platelet phosphorylated TDP-43: An exploratory study for a peripheral surrogate biomarker development for Alzheimer’s disease

2017 ◽  
Author(s):  
Rodger Wilhite ◽  
Jessica Sage ◽  
Abdurrahman Bouzid ◽  
Tyler Primavera ◽  
Abdulbaki Agbas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Signs ◽  
Brain Regions ◽  
Post Mortem ◽  
Disease Prognosis ◽  
Post Mortem Brain ◽  
And Control ◽  
Lateral Sclerosis

AbstractAim: Alzheimer’s disease (AD) and other forms of dementia create a non-curable disease population in World’s societies. To develop a blood-based biomarker is important so that the remedial or disease-altering therapeutic intervention for AD patients would be available at the early stage. Materials & Methods: TDP-43 levels were analyzed in post-mortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in post-mortem AD brain regions and similar trends were also observed in patient’s platelets. Conclusion: Platelet TDP-43 could be used as a surrogate biomarker that is measurable, reproducible, and sensitive for screening the patients with some early clinical signs of AD and can be used to monitor disease prognosis.Lay abstractIn this study, we explore to identify an Alzheimer’s disease-selective phospho-specific antibody that recognizes the diseased form of TDP-43 protein in patient’s blood-derived platelets. Our results suggest that selective anti-phosphorylated TDP-43 antibody discriminates Alzheimer’s disease from non-demented controls and patients with amyotrophic lateral sclerosis. Therefore, platelet screening with a selective antibody could potentially be a useful tool for diagnostic purposes for Alzheimer’s disease.

scholarly journals Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides

2021 ◽  
Vol 12 ◽  
Author(s):  
Liam Anuj O'Leary ◽  
Claudia Belliveau ◽  
Maria Antonietta Davoli ◽  
Jie Christopher Ma ◽  
Arnaud Tanti ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Vessels ◽  
Close Association ◽  
Brain Regions ◽  
Quantitative Comparison ◽  
Post Mortem ◽  
Dorsomedial Prefrontal Cortex ◽  
Post Mortem Brain ◽  
Morphometric Features ◽  
Fine Morphology

Post-mortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in post-mortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

scholarly journals Single-cell deconvolution of 3,000 post-mortem brain samples for eQTL and GWAS dissection in mental disorders

2021 ◽  
Author(s):  
Yongjin Park ◽  
Liang He ◽  
Jose Davila-Velderrain ◽  
Lei Hou ◽  
Shahin Mohammadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Genetic Variants ◽  
Cell Types ◽  
Brain Regions ◽  
Post Mortem ◽  
Rna Seq ◽  
Cell Type ◽  
Post Mortem Brain ◽  
Cell Type Specific

AbstractThousands of genetic variants acting in multiple cell types underlie complex disorders, yet most gene expression studies profile only bulk tissues, making it hard to resolve where genetic and non-genetic contributors act. This is particularly important for psychiatric and neurodegenerative disorders that impact multiple brain cell types with highly-distinct gene expression patterns and proportions. To address this challenge, we develop a new framework, SPLITR, that integrates single-nucleus and bulk RNA-seq data, enabling phenotype-aware deconvolution and correcting for systematic discrepancies between bulk and single-cell data. We deconvolved 3,387 post-mortem brain samples across 1,127 individuals and in multiple brain regions. We find that cell proportion varies across brain regions, individuals, disease status, and genotype, including genetic variants in TMEM106B that impact inhibitory neuron fraction and 4,757 cell-type-specific eQTLs. Our results demonstrate the power of jointly analyzing bulk and single-cell RNA-seq to provide insights into cell-type-specific mechanisms for complex brain disorders.

Neurochemical differences in two rat strains exposed to social isolation rearing

2012 ◽  
Vol 24 (5) ◽  
pp. 286-295 ◽  
Author(s):  
Luigia Trabace ◽  
Margherita Zotti ◽  
Marilena Colaianna ◽  
Maria G. Morgese ◽  
Stefania Schiavone ◽  
...  
Keyword(s):  
High Performance ◽  
Tissue Concentration ◽  
Brain Area ◽  
Brain Regions ◽  
Post Mortem ◽  
Isolation Rearing ◽  
Post Mortem Brain ◽  
Rat Strain ◽  
Neurochemical Changes

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation.Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography.Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions.Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.

BDNF and NT3 concentrations in post-mortem brain tissue of individuals with recurrent depressive disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 689-689
Author(s):  
A.J. Sheldrick ◽  
S. Camara ◽  
P. Riederer ◽  
T.M. Michel
Keyword(s):  
Depressive Disorder ◽  
Brain Tissue ◽  
Antidepressant Treatment ◽  
Brain Regions ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
Neurotrophin 3 ◽  
Therapeutic Mechanism ◽  
Icd 10 ◽  
History Of

IntroductionNeurotrophines such as brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) have been implicated in the pathogenesis of depression and the therapeutic mechanism of antidepressants. Several clinical studies on depressive disorder (DD) have shown that levels of blood BDNF are diminished in depression and increase during antidepressant treatment. So far, only few studies have examined concentrations of neurotrophic factors in post-mortem brain tissue of individuals who suffered from DD.Objectives/aimsThe objective of the study was to show whether BDNF and NT3 levels in post-mortem brain tissue of individuals who suffered from recurrent DD and who had been treated with antidepressants differed compared to controls.MethodsSpecimens from cortical and limbic areas of post-mortem brain tissue of 7 individuals with an ante-mortem diagnosis of recurrent depressive disorder based on ICD-10 criteria (F33.0–F33.8) who received no psychotropic medication other than selective serotonin re-uptake inhibitors 6 months preceding death were selected. We compared the concentrations of BDNF and NT3 with 14 matched controls without any history of psychiatric disorder or treatment with psychotropic drugs.ResultsWe detected no significant differences of either NT 3 or BDNF concentrations in any of the brain regions examined in patients who had suffered from DD and had been treated with antidepressants compared to controls.ConclusionsThese findings could be interpreted as a neurotrophic effect of antidepressant treatment in patients with recurrent DD, supporting the notion that depression improvement is associated with neuroplastic changes. However, more research using post-mortem brain tissue is needed.

scholarly journals Integrated miRNA-Seq and mRNA-Seq Study to Identify miRNAs Associated With Alzheimer’s Disease Using Post-mortem Brain Tissue Samples

2021 ◽  
Vol 15 ◽  
Author(s):  
Qingqin S. Li ◽  
Diana Cai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Inferior Frontal Gyrus ◽  
Wnt Signaling Pathway ◽  
Amyloid Β ◽  
Brain Regions ◽  
Differentially Expressed ◽  
Post Mortem ◽  
Post Mortem Brain

Alzheimer’s disease (AD), the leading form of dementia, is associated with abnormal tau and β-amyloid accumulation in the brain. We conducted a miRNA-seq study to identify miRNAs associated with AD in the post-mortem brain from the inferior frontal gyrus (IFG, n = 69) and superior temporal gyrus (STG, n = 81). Four and 64 miRNAs were differentially expressed (adjusted p-value &lt; 0.05) in AD compared to cognitively normal controls in the IFG and STG, respectively. We observed down-regulation of several miRNAs that have previously been implicated in AD, including hsa-miR-212-5p and hsa-miR-132-5p, in AD samples across both brain regions, and up-regulation of hsa-miR-146a-5p, hsa-miR-501-3p, hsa-miR-34a-5p, and hsa-miR-454-3p in the STG. The differentially expressed miRNAs were previously implicated in the formation of amyloid-β plaques, the dysregulation of tau, and inflammation. We have also observed differential expressions for dozens of other miRNAs in the STG, including hsa-miR-4446-3p, that have not been described previously. Putative targets of these miRNAs (adjusted p-value &lt; 0.1) were found to be involved in Wnt signaling pathway, MAPK family signaling cascades, sphingosine 1-phosphate (S1P) pathway, adaptive immune system, innate immune system, and neurogenesis. Our results support the finding of dysregulated miRNAs previously implicated in AD and propose additional miRNAs that appear to be dysregulated in AD for experimental follow-up.

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