scholarly journals Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing

2021 ◽  
Vol 7 (4) ◽  
pp. e608
Author(s):  
Charles Jourdan Reyes ◽  
Björn-Hergen Laabs ◽  
Susen Schaake ◽  
Theresa Lüth ◽  
Raphaela Ardicoglu ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Regional Differences ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Nanopore Sequencing ◽  
Disease Manifestation ◽  
Repeat Instability ◽  
Hexanucleotide Repeat ◽  
Oxford Nanopore ◽  
Small Pool

ObjectiveOur study investigated the presence of regional differences in hexanucleotide repeat number in postmortem brain tissues of 2 patients with X-linked dystonia-parkinsonism (XDP), a combined dystonia-parkinsonism syndrome modified by a (CCCTCT)n repeat within the causal SINE-VNTR-Alu retrotransposon insertion in the TAF1 gene.MethodsGenomic DNA was extracted from blood and postmortem brain samples, including the basal ganglia and cortex from both patients and from the cerebellum, midbrain, and pituitary gland from 1 patient. Repeat sizing was performed using fragment analysis, small-pool PCR-based Southern blotting, and Oxford nanopore sequencing.ResultsThe basal ganglia (p < 0.001) and cerebellum (p < 0.001) showed higher median repeat numbers and higher degrees of repeat instability compared with blood.ConclusionsSomatic repeat instability may predominate in brain regions selectively affected in XDP, thereby hinting at its potential role in disease manifestation and modification.

scholarly journals Mesolimbic microglia display regionally distinct developmental trajectories

2019 ◽  
Author(s):  
KT Hope ◽  
IA Hawes ◽  
A Bonci ◽  
LM De Biase
Keyword(s):  
Basal Ganglia ◽  
Regional Differences ◽  
Time Course ◽  
Developmental Trajectories ◽  
Tissue Expansion ◽  
Brain Regions ◽  
The Third ◽  
Density Peaks ◽  
Microglial Phenotype ◽  
Developmental Window

ABSTRACTMicroglia play critical roles during CNS development and undergo dramatic changes in tissue distribution, morphology, and gene expression as they transition from embryonic to neonatal to adult microglial phenotypes. Despite the magnitude of these phenotypic shifts, little is known about the time course and dynamics of these transitions and whether they vary across brain regions. Here we define the time course of microglial maturation in key regions of the basal ganglia in mice where significant regional differences in microglial phenotype are present in adults. We found that microglial density peaks in the ventral tegmental area (VTA) and nucleus accumbens (NAc) during the third postnatal week, driven by a burst of microglial proliferation. Microglial abundance is then refined to adult levels through a combination of tissue expansion and microglial programmed cell death. This overproduction and refinement of microglia was significantly more pronounced in the NAc and was accompanied by a sharp peak in NAc microglial lysosome abundance in the third postnatal week. Collectively, these data identify a key developmental window when elevated microglial density in discrete basal ganglia nuclei may support circuit refinement and could increase susceptibility to inflammatory insults.

scholarly journals Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cody L. Call ◽  
Dwight E. Bergles
Keyword(s):  
Cortical Neurons ◽  
Regional Differences ◽  
Brain Regions ◽  
Axon Diameter ◽  
Neuronal Identity ◽  
Cortical Areas ◽  
Myelin Sheaths ◽  
Parvalbumin Interneurons ◽  
Selection Of

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

scholarly journals In vivo synaptic density relates to glucose metabolism at rest in healthy subjects, but is strongly modulated by regional differences

2021 ◽  
pp. 0271678X2098150
Author(s):  
June van Aalst ◽  
Jenny Ceccarini ◽  
Stefan Sunaert ◽  
Patrick Dupont ◽  
Michel Koole ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Medial Temporal Lobe ◽  
Regional Differences ◽  
Specific Binding ◽  
Aerobic Glycolysis ◽  
Glucose Consumption ◽  
Brain Regions ◽  
Synaptic Density ◽  
Energy Demands

Preclinical and postmortem studies have suggested that regional synaptic density and glucose consumption (CMRGlc) are strongly related. However, the relation between synaptic density and cerebral glucose metabolism in the human brain has not directly been assessed in vivo. Using [11C]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A) as indicator for synaptic density and [18F]FDG for measuring cerebral glucose consumption, we studied twenty healthy female subjects (age 29.6 ± 9.9 yrs) who underwent a single-day dual-tracer protocol (GE Signa PET-MR). Global measures of absolute and relative CMRGlc and specific binding of [11C]UCB-J were indeed highly significantly correlated ( r > 0.47, p < 0.001). However, regional differences in relative [18F]FDG and [11C]UCB-J uptake were observed, with up to 19% higher [11C]UCB-J uptake in the medial temporal lobe (MTL) and up to 17% higher glucose metabolism in frontal and motor-related areas and thalamus. This pattern has a considerable overlap with the brain regions showing different levels of aerobic glycolysis. Regionally varying energy demands of inhibitory and excitatory synapses at rest may also contribute to this difference. Being unaffected by astroglial and/or microglial energy demands, changes in synaptic density in the MTL may therefore be more sensitive to early detection of pathological conditions compared to changes in glucose metabolism.

scholarly journals Heritability and interindividual variability of regional structure-function coupling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zijin Gu ◽  
Keith Wakefield Jamison ◽  
Mert Rory Sabuncu ◽  
Amy Kuceyeski
Keyword(s):  
Functional Connectivity ◽  
Structure Function ◽  
Regional Differences ◽  
Regional Scale ◽  
Brain Regions ◽  
Diffusion Weighted Mri ◽  
Regional Structure ◽  
Human Connectome Project ◽  
Structural Connections ◽  
The Relationship

AbstractWhite matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.

scholarly journals Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  
Keyword(s):  
Neural Development ◽  
Protein Level ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Pathophysiological Mechanism ◽  
Brain Disorders ◽  
Spine Density ◽  
Genes Encoding ◽  
High Level ◽  
And Function

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.

scholarly journals Genome and transcriptome of a pathogenic yeast, Candida nivariensis

2021 ◽  
Author(s):  
Yunfan Fan ◽  
Andrew N Gale ◽  
Anna Bailey ◽  
Kali Barnes ◽  
Kiersten Colotti ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Glabrata ◽  
Nanopore Sequencing ◽  
Cdna Sequencing ◽  
Pathogenic Yeast ◽  
Mitochondrial Sequence ◽  
Dna And Rna ◽  
Oxford Nanopore ◽  
Candida Nivariensis ◽  
Oxford Nanopore Technologies

Abstract We present a highly contiguous genome and transcriptome of the pathogenic yeast, Candida nivariensis. We sequenced both the DNA and RNA of this species using both the Oxford Nanopore Technologies (ONT) and Illumina platforms. We assembled the genome into an 11.8 Mb draft composed of 16 contigs with an N50 of 886 Kb, including a circular mitochondrial sequence of 28 Kb. Using direct RNA nanopore sequencing and Illumina cDNA sequencing, we constructed an annotation of our new assembly, supplemented by lifting over genes from Saccharomyces cerevisiae and Candida glabrata.

scholarly journals High resolution species detection: accurate long read eDNA metabarcoding of North Sea fish using Oxford Nanopore sequencing

2021 ◽  
Author(s):  
Karlijn Doorenspleet ◽  
Lara Jansen ◽  
Saskia Oosterbroek ◽  
Oscar Bos ◽  
Pauline Kamermans ◽  
...  
Keyword(s):  
High Resolution ◽  
North Sea ◽  
Fish Species ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
Nanopore Sequencing ◽  
Nature Restoration ◽  
Oxford Nanopore ◽  
Field Samples ◽  
Long Read

To monitor the effect of nature restoration projects in North Sea ecosystems, accurate and intensive biodiversity assessments are vital. DNA based techniques and especially environmental DNA (eDNA) metabarcoding from seawater is becoming a powerful monitoring tool. However, current approaches are based on genetic target regions of <500 nucleotides, which offer limited taxonomic resolution. This study aims to develop and validate a long read nanopore sequencing method for eDNA that enables improved identification of fish species. We designed a universal primer pair targeting a 2kb region covering the 12S and 16S rRNA genes of fish mitochondria. eDNA was amplified and sequenced using the Oxford Nanopore MiniON. Sequence data was processed using the new pipeline Decona, and accurate consensus identities of above 99.9% were retrieved. The primer set efficiency was tested with eDNA from a 3.000.000 L zoo aquarium with 31 species of bony fish and elasmobranchs. Over 55% of the species present were identified on species level and over 75% on genus level. Next, our long read eDNA metabarcoding approach was applied to North Sea eDNA field samples collected at ship wreck sites, the Gemini Offshore Wind Farm, the Borkum Reef Grounds and a bare sand bottom. Here, location specific fish and vertebrate communities were obtained. Incomplete reference databases still form a major bottleneck in further developing high resolution long read metabarcoding. Yet, the method has great potential for rapid and accurate fish species monitoring in marine field studies.

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