Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 551.275
Filtrar
1.
Nat Commun ; 15(1): 5587, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961076

RESUMO

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.


Assuntos
Alelos , Metilação de DNA , Animais , Suínos/genética , Feminino , Cromatina/genética , Cromatina/metabolismo , Especificidade de Órgãos/genética , Fígado/metabolismo , Placenta/metabolismo , Masculino , Encéfalo/metabolismo , Sus scrofa/genética , Sequenciamento Completo do Genoma , Gravidez , Multiômica
2.
Sci Rep ; 14(1): 15270, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961114

RESUMO

Alzheimer's disease (AD), the predominant form of dementia, is a growing global challenge, emphasizing the urgent need for accurate and early diagnosis. Current clinical diagnoses rely on radiologist expert interpretation, which is prone to human error. Deep learning has thus far shown promise for early AD diagnosis. However, existing methods often overlook focal structural atrophy critical for enhanced understanding of the cerebral cortex neurodegeneration. This paper proposes a deep learning framework that includes a novel structure-focused neurodegeneration CNN architecture named SNeurodCNN and an image brightness enhancement preprocessor using gamma correction. The SNeurodCNN architecture takes as input the focal structural atrophy features resulting from segmentation of brain structures captured through magnetic resonance imaging (MRI). As a result, the architecture considers only necessary CNN components, which comprises of two downsampling convolutional blocks and two fully connected layers, for achieving the desired classification task, and utilises regularisation techniques to regularise learnable parameters. Leveraging mid-sagittal and para-sagittal brain image viewpoints from the Alzheimer's disease neuroimaging initiative (ADNI) dataset, our framework demonstrated exceptional performance. The para-sagittal viewpoint achieved 97.8% accuracy, 97.0% specificity, and 98.5% sensitivity, while the mid-sagittal viewpoint offered deeper insights with 98.1% accuracy, 97.2% specificity, and 99.0% sensitivity. Model analysis revealed the ability of SNeurodCNN to capture the structural dynamics of mild cognitive impairment (MCI) and AD in the frontal lobe, occipital lobe, cerebellum, temporal, and parietal lobe, suggesting its potential as a brain structural change digi-biomarker for early AD diagnosis. This work can be reproduced using code we made available on GitHub.


Assuntos
Doença de Alzheimer , Aprendizado Profundo , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/classificação , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
3.
Commun Biol ; 7(1): 810, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961130

RESUMO

The associative theory of creativity proposes that creative ideas result from connecting remotely related concepts in memory. Previous research found that higher creative individuals exhibit a more flexible organization of semantic memory, generate more uncommon word associations, and judge remote concepts as more related. In this study (N = 93), we used fMRI to investigate brain regions involved in judging the relatedness of concepts that vary in their semantic distance, and how such neural involvement relates to individual differences in creativity. Brain regions where activity increased with semantic relatedness mainly overlapped with default, control, salience, semantic control, and multiple demand networks. The default and semantic control networks exhibited increased involvement when evaluating more remote associations. Finally, higher creative people, who provided higher relatedness judgements on average, exhibited lower activity in those regions, possibly reflecting higher neural efficiency. We discuss these findings in the context of the neurocognitive processing underlying creativity. Overall, our findings indicate that judging remote concepts as related reflects a cognitive mechanism underlying creativity and shed light on the neural correlates of this mechanism.


Assuntos
Encéfalo , Criatividade , Imageamento por Ressonância Magnética , Semântica , Humanos , Masculino , Feminino , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Adulto Jovem , Adulto , Mapeamento Encefálico/métodos , Memória/fisiologia
4.
Sci Rep ; 14(1): 15338, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961135

RESUMO

Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( v p ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and v p from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (ß = - 2.9; p = 0.006), basal ganglia (ß = - 2.3; p = 0.04), white matter (ß = - 2.6; p = 0.04), whole-brain (ß = - 2.7; p = 0.04) and borderline-related for cortex (ß = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.


Assuntos
Barreira Hematoencefálica , Cognição , Imageamento por Ressonância Magnética , Humanos , Barreira Hematoencefálica/diagnóstico por imagem , Idoso , Masculino , Feminino , Cognição/fisiologia , Idoso de 80 Anos ou mais , Fluxo Pulsátil , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiologia , Estudos Prospectivos , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/irrigação sanguínea , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem
5.
J Neurodev Disord ; 16(1): 36, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961335

RESUMO

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Síndrome de Rett , Humanos , Síndrome de Rett/diagnóstico por imagem , Síndrome de Rett/fisiopatologia , Síndrome de Rett/patologia , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/crescimento & desenvolvimento , Adulto , Criança , Adulto Jovem , Pré-Escolar , Adolescente , Taiwan , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Masculino , Tamanho do Órgão , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
6.
J Neuroinflammation ; 21(1): 169, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961424

RESUMO

BACKGROUND: Understanding the mechanism behind sepsis-associated encephalopathy (SAE) remains a formidable task. This study endeavors to shed light on the complex cellular and molecular alterations that occur in the brains of a mouse model with SAE, ultimately unraveling the underlying mechanisms of this condition. METHODS: We established a murine model using intraperitoneal injection of lipopolysaccharide (LPS) in wild type and Anxa1-/- mice and collected brain tissues for analysis at 0-hour, 12-hour, 24-hour, and 72-hour post-injection. Utilizing advanced techniques such as single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq, we conducted a comprehensive characterization of the cellular responses and molecular patterns within the brain. RESULTS: Our study uncovered notable temporal differences in the response to LPS challenge between Anxa1-/- (annexin A1 knockout) and wild type mice, specifically at the 12-hour and 24-hour time points following injection. We observed a significant increase in the proportion of Astro-2 and Micro-2 cells in these mice. These cells exhibited a colocalization pattern with the vascular subtype Vas-1, forming a distinct region known as V1A2M2, where Astro-2 and Micro-2 cells surrounded Vas-1. Moreover, through further analysis, we discovered significant upregulation of ligands and receptors such as Timp1-Cd63, Timp1-Itgb1, Timp1-Lrp1, as well as Ccl2-Ackr1 and Cxcl2-Ackr1 within this region. In addition, we observed a notable increase in the expression of Cd14-Itgb1, Cd14-Tlr2, and Cd14-C3ar1 in regions enriched with Micro-2 cells. Additionally, Cxcl10-Sdc4 showed broad upregulation in brain regions containing both Micro-2 and Astro-2 cells. Notably, upon LPS challenge, there was an observed increase in Anxa1 expression in the mouse brain. Furthermore, our study revealed a noteworthy increase in mortality rates following Anxa1 knockdown. However, we did not observe substantial differences in the types, numbers, or distribution of other brain cells between Anxa1-/- and wildtype mice over time. Nevertheless, when comparing the 24-hour post LPS injection time point, we observed a significant decrease in the proportion and distribution of Micro-2 and Astro-2 cells in the vicinity of blood vessels in Anxa1-/- mice. Additionally, we noted reduced expression levels of several ligand-receptor pairs including Cd14-Tlr2, Cd14-C3ar1, Cd14-Itgb1, Cxcl10-Sdc4, Ccl2-Ackr1, and Cxcl2-Ackr1. CONCLUSIONS: By combining snRNA-seq and Stereo-seq techniques, our study successfully identified a distinctive cellular colocalization, referred to as a special pathological niche, comprising Astro-2, Micro-2, and Vas-1 cells. Furthermore, we observed an upregulation of ligand-receptor pairs within this niche. These findings suggest a potential association between this cellular arrangement and the underlying mechanisms contributing to SAE or the increased mortality observed in Anxa1 knockdown mice.


Assuntos
Astrócitos , Encéfalo , Modelos Animais de Doenças , Lipopolissacarídeos , Camundongos Knockout , Microglia , Encefalopatia Associada a Sepse , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Encefalopatia Associada a Sepse/patologia , Encefalopatia Associada a Sepse/genética , Encefalopatia Associada a Sepse/metabolismo , Microglia/metabolismo , Microglia/patologia , Encéfalo/patologia , Encéfalo/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Análise de Sequência de RNA/métodos , Camundongos Endogâmicos C57BL , Transcriptoma , Masculino
7.
Genome Biol ; 25(1): 175, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961490

RESUMO

BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.


Assuntos
Cromatina , Histona-Lisina N-Metiltransferase , Células-Tronco Neurais , Elementos Nucleotídeos Curtos e Dispersos , Animais , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Camundongos , Cromatina/metabolismo , Metilação de DNA , Fator de Ligação a CCCTC/metabolismo , Fator de Ligação a CCCTC/genética , Epigênese Genética , Histonas/metabolismo , Encéfalo/metabolismo , Encéfalo/citologia
9.
F1000Res ; 13: 691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962692

RESUMO

Background: Non-contrast Computed Tomography (NCCT) plays a pivotal role in assessing central nervous system disorders and is a crucial diagnostic method. Iterative reconstruction (IR) methods have enhanced image quality (IQ) but may result in a blotchy appearance and decreased resolution for subtle contrasts. The deep-learning image reconstruction (DLIR) algorithm, which integrates a convolutional neural network (CNN) into the reconstruction process, generates high-quality images with minimal noise. Hence, the objective of this study was to assess the IQ of the Precise Image (DLIR) and the IR technique (iDose 4) for the NCCT brain. Methods: This is a prospective study. Thirty patients who underwent NCCT brain were included. The images were reconstructed using DLIR-standard and iDose 4. Qualitative IQ analysis parameters, such as overall image quality (OQ), subjective image noise (SIN), and artifacts, were measured. Quantitative IQ analysis parameters such as Computed Tomography (CT) attenuation (HU), image noise (IN), posterior fossa index (PFI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the basal ganglia (BG) and centrum-semiovale (CSO) were measured. Paired t-tests were performed for qualitative and quantitative IQ analyses between the iDose 4 and DLIR-standard. Kappa statistics were used to assess inter-observer agreement for qualitative analysis. Results: Quantitative IQ analysis showed significant differences (p<0.05) in IN, SNR, and CNR between the iDose 4 and DLIR-standard at the BG and CSO levels. IN was reduced (41.8-47.6%), SNR (65-82%), and CNR (68-78.8%) were increased with DLIR-standard. PFI was reduced (27.08%) the DLIR-standard. Qualitative IQ analysis showed significant differences (p<0.05) in OQ, SIN, and artifacts between the DLIR standard and iDose 4. The DLIR standard showed higher qualitative IQ scores than the iDose 4. Conclusion: DLIR standard yielded superior quantitative and qualitative IQ compared to the IR technique (iDose4). The DLIR-standard significantly reduced the IN and artifacts compared to iDose 4 in the NCCT brain.


Assuntos
Encéfalo , Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Projetos Piloto , Feminino , Tomografia Computadorizada por Raios X/métodos , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Adulto , Processamento de Imagem Assistida por Computador/métodos , Idoso , Razão Sinal-Ruído , Algoritmos
10.
Neuron ; 112(13): 2081-2083, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964282

RESUMO

Preterm infants can face lasting neurodevelopmental challenges due to hypoxia-induced injury of the cerebral white matter. In this issue of Neuron, Ren et al.1 identify microvascular pericytes as unexpected targets for growth hormone signaling, which enhances angiogenesis and remyelination after hypoxic injury in the developing mouse brain.


Assuntos
Hipóxia Encefálica , Bainha de Mielina , Pericitos , Pericitos/metabolismo , Bainha de Mielina/metabolismo , Animais , Hipóxia Encefálica/metabolismo , Camundongos , Humanos , Animais Recém-Nascidos , Encéfalo/metabolismo
11.
J Psycholinguist Res ; 53(4): 59, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967726

RESUMO

This study was conducted with the aim of exploring the general parsing mechanisms involved in processing different kinds of dependency relations, namely verb agreement with subjects versus objects in Punjabi, an SOV Indo-Aryan language. Event related brain potentials (ERPs) were recorded as twenty-five native Punjabi speakers read transitive sentences. Critical stimuli were either fully acceptable as regards verb agreement, or alternatively violated gender agreement with the subject or object. A linear mixed-models analysis confirmed a P600 effect at the position of the verb for all violations, regardless of whether subject or object agreement was violated. These results thus suggest that an identical mechanism is involved in gender agreement computation in Punjabi regardless of whether the agreement is with the subject or the object argument.


Assuntos
Eletroencefalografia , Potenciais Evocados , Idioma , Psicolinguística , Humanos , Potenciais Evocados/fisiologia , Feminino , Masculino , Adulto , Adulto Jovem , Leitura , Encéfalo/fisiologia
12.
Brain Behav ; 14(7): e3619, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38970221

RESUMO

OBJECTIVE: Normal aging is associated with brain volume change, and brain segmentation can be performed within an acceptable scan time using synthetic magnetic resonance imaging (MRI). This study aimed to investigate the brain volume changes in healthy adult according to age and gender, and provide age- and gender-specific reference values using synthetic MRI. METHODS: A total of 300 healthy adults (141 males, median age 48; 159 females, median age 50) were underwent synthetic MRI on 3.0 T. Brain parenchymal volume (BPV), gray matter volume (GMV), white matter volume (WMV), myelin volume (MYV), and cerebrospinal fluid volume (CSFV) were calculated using synthetic MRI software. These volumes were normalized by intracranial volume to normalized GMV (nGMV), normalized WMV (nWMV), normalized MYV (nMYV), normalized BPV (nBPV), and normalized CSFV (nCSFV). The normalized brain volumes were plotted against age in both males and females, and a curve fitting model that best explained the age dependence of brain volume was identified. The normalized brain volumes were compared between different age and gender groups. RESULTS: The approximate curves of nGMV, nWMV, nCSFV, nBPV, and nMYV were best fitted by quadratic curves. The nBPV decreased monotonously through all ages in both males and females, while the changes of nCSFV showed the opposite trend. The nWMV and nMYV in both males and females increased gradually and then decrease with age. In early adulthood (20s), nWMV and nMYV in males were lower and peaked later than that in females (p < .005). The nGMV in both males and females decreased in the early adulthood until the 30s and then remains stable. A significant decline in nWMV, nBPV, and nMYV was noted in the 60s (Turkey test, p < .05). CONCLUSIONS: Our study provides age- and gender-specific reference values of brain volumes using synthetic MRI, which could be objective tools for discriminating brain disorders from healthy brains.


Assuntos
Envelhecimento , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Adulto , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Envelhecimento/fisiologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/anatomia & histologia , Tamanho do Órgão/fisiologia , Fatores Sexuais , Substância Branca/diagnóstico por imagem , Valores de Referência , Caracteres Sexuais , Fatores Etários
13.
Hum Brain Mapp ; 45(10): e26770, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38970217

RESUMO

Alpha oscillations are known to play a central role in several higher-order cognitive functions, especially selective attention, working memory, semantic memory, and creative thinking. Nonetheless, we still know very little about the role of alpha in the generation of more remote semantic associations, which is key to creative and semantic cognition. Furthermore, it remains unclear how these oscillations are shaped by the intention to "be creative," which is the case in most creativity tasks. We aimed to address these gaps in two experiments. In Experiment 1, we compared alpha oscillatory activity (using a method which distinguishes genuine oscillatory activity from transient events) during the generation of free associations which were more vs. less distant from a given concept. In Experiment 2, we replicated these findings and also compared alpha oscillatory activity when people were generating free associations versus associations with the instruction to be creative (i.e. goal-directed). We found that alpha was consistently higher during the generation of more distant semantic associations, in both experiments. This effect was widespread, involving areas in both left and right hemispheres. Importantly, the instruction to be creative seems to increase alpha phase synchronisation from left to right temporal brain areas, suggesting that intention to be creative changed the flux of information in the brain, likely reflecting an increase in top-down control of semantic search processes. We conclude that goal-directed generation of remote associations relies on top-down mechanisms compared to when associations are freely generated.


Assuntos
Ritmo alfa , Criatividade , Objetivos , Semântica , Humanos , Ritmo alfa/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Associação , Eletroencefalografia , Adolescente
14.
Brain Behav ; 14(7): e3621, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38970239

RESUMO

INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.


Assuntos
Encefalopatia Hepática , Lactulose , Ratos Sprague-Dawley , Rifaximina , Animais , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/metabolismo , Rifaximina/farmacologia , Ratos , Masculino , Lactulose/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Modelos Animais de Doenças , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/diagnóstico por imagem , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/administração & dosagem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Radioisótopos de Flúor , Proteínas de Transporte , Receptores de GABA-A
15.
Wiley Interdiscip Rev RNA ; 15(4): e1865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972934

RESUMO

The brain is a complex computing system composed of a multitude of interacting neurons. The computational outputs of this system determine the behavior and perception of every individual. Each brain cell expresses thousands of genes that dictate the cell's function and physiological properties. Therefore, deciphering the molecular expression of each cell is of great significance for understanding its characteristics and role in brain function. Additionally, the positional information of each cell can provide crucial insights into their involvement in local brain circuits. In this review, we briefly overview the principles of single-cell RNA sequencing and spatial transcriptomics, the potential issues and challenges in their data processing, and their applications in brain research. We further outline several promising directions in neuroscience that could be integrated with single-cell RNA sequencing, including neurodevelopment, the identification of novel brain microstructures, cognition and behavior, neuronal cell positioning, molecules and cells related to advanced brain functions, sleep-wake cycles/circadian rhythms, and computational modeling of brain function. We believe that the deep integration of these directions with single-cell and spatial RNA sequencing can contribute significantly to understanding the roles of individual cells or cell types in these specific functions, thereby making important contributions to addressing critical questions in those fields. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Development RNA in Disease and Development > RNA in Disease.


Assuntos
Encéfalo , Análise de Sequência de RNA , Análise de Célula Única , Análise de Célula Única/métodos , Encéfalo/metabolismo , Humanos , Animais , Análise de Sequência de RNA/métodos
16.
J Biosci ; 492024.
Artigo em Inglês | MEDLINE | ID: mdl-38973668

RESUMO

Itch is a unique sensory experience that is responded to by scratching. How pruritogens, which are mechanical and chemical stimuli with the potential to cause itch, engage specific pathways in the peripheral and central nervous system has been a topic of intense investigation over the last few years. Studies employing recently developed molecular, physiological, and behavioral techniques have delineated the dedicated mechanisms that transmit itch information to the brain. This review outlines the genetically defined and evolutionary conserved circuits for itch ranging from the skin-innervating peripheral neurons to the cortical neurons that drive scratching. Moreover, scratch suppression of itch is attributed to the concurrent activation of pain and itch pathways. Hence, we discuss the similarities between circuits driving pain and itch.


Assuntos
Vias Neurais , Prurido , Prurido/fisiopatologia , Prurido/patologia , Prurido/genética , Humanos , Animais , Neurônios/metabolismo , Pele/patologia , Dor/patologia , Dor/fisiopatologia , Dor/genética , Encéfalo/fisiopatologia
17.
Dialogues Clin Neurosci ; 26(1): 38-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38963341

RESUMO

INTRODUCTION: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. METHODS: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. RESULTS: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. CONCLUSION: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Masculino , Feminino , Idoso , Encéfalo/patologia , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Resultado do Tratamento , Transtornos Cognitivos/terapia , Depressão/terapia , Fatores Etários , Valor Preditivo dos Testes
18.
Transl Psychiatry ; 14(1): 276, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965206

RESUMO

Suicide is a growing public health problem around the world. The most important risk factor for suicide is underlying psychiatric illness, especially depression. Detailed classification of suicide in patients with depression can greatly enhance personalized suicide control efforts. This study used unstructured psychiatric charts and brain magnetic resonance imaging (MRI) records from a psychiatric outpatient clinic to develop a machine learning-based suicidal thought classification model. The study included 152 patients with new depressive episodes for development and 58 patients from a geographically different hospital for validation. We developed an eXtreme Gradient Boosting (XGBoost)-based classification models according to the combined types of data: independent components-map weightings from brain T1-weighted MRI and topic probabilities from clinical notes. Specifically, we used 5 psychiatric symptom topics and 5 brain networks for models. Anxiety and somatic symptoms topics were significantly more common in the suicidal group, and there were group differences in the default mode and cortical midline networks. The clinical symptoms plus structural brain patterns model had the highest area under the receiver operating characteristic curve (0.794) versus the clinical notes only and brain MRI only models (0.748 and 0.738, respectively). The results were consistent across performance metrics and external validation. Our findings suggest that focusing on personalized neuroimaging and natural language processing variables improves evaluation of suicidal thoughts.


Assuntos
Transtorno Depressivo Maior , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Processamento de Linguagem Natural , Neuroimagem , Ideação Suicida , Humanos , Feminino , Transtorno Depressivo Maior/diagnóstico por imagem , Masculino , Adulto , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Adulto Jovem , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia
19.
Sci Rep ; 14(1): 15432, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965248

RESUMO

Previous research has primarily employed deep learning models such as Convolutional Neural Networks (CNNs), and Recurrent Neural Networks (RNNs) for decoding imagined character signals. These approaches have treated the temporal and spatial features of the signals in a sequential, parallel, or single-feature manner. However, there has been limited research on the cross-relationships between temporal and spatial features, despite the inherent association between channels and sampling points in Brain-Computer Interface (BCI) signal acquisition, which holds significant information about brain activity. To address the limited research on the relationships between temporal and spatial features, we proposed a Temporal-Spatial Cross-Attention Network model, named TSCA-Net. The TSCA-Net is comprised of four modules: the Temporal Feature (TF), the Spatial Feature (SF), the Temporal-Spatial Cross (TSCross), and the Classifier. The TF combines LSTM and Transformer to extract temporal features from BCI signals, while the SF captures spatial features. The TSCross is introduced to learn the correlations between the temporal and spatial features. The Classifier predicts the label of BCI data based on its characteristics. We validated the TSCA-Net model using publicly available datasets of handwritten characters, which recorded the spiking activity from two micro-electrode arrays (MEAs). The results showed that our proposed TSCA-Net outperformed other comparison models (EEG-Net, EEG-TCNet, S3T, GRU, LSTM, R-Transformer, and ViT) in terms of accuracy, precision, recall, and F1 score, achieving 92.66 % , 92.77 % , 92.70 % , and 92.58 % , respectively. The TSCA-Net model demonstrated a 3.65 % to 7.49 % improvement in accuracy over the comparison models.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Redes Neurais de Computação , Humanos , Eletroencefalografia/métodos , Imaginação/fisiologia , Encéfalo/fisiologia , Atenção/fisiologia , Aprendizado Profundo , Processamento de Sinais Assistido por Computador
20.
Nat Commun ; 15(1): 5627, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965283

RESUMO

Glycosphingolipids (GSLs) are essential components of cell membranes, particularly enriched in the nervous system. Altered molecular distributions of GSLs are increasingly associated with human diseases, emphasizing the significance of lipidomic profiling. Traditional GSL analysis methods are hampered by matrix effect from phospholipids and the difficulty in distinguishing structural isomers. Herein, we introduce a highly sensitive workflow that harnesses magnetic TiO2 nanoparticle-based selective enrichment, charge-tagging Paternò-Büchi reaction, and liquid chromatography-tandem mass spectrometry. This approach enables mapping over 300 distinct GSLs in brain tissues by defining sugar types, long chain bases, N-acyl chains, and the locations of desaturation and hydroxylation. Relative quantitation of GSLs across multiple structural levels provides evidence of dysregulated gene and protein expressions of FA2H and CerS2 in human glioma tissue. Based on the structural features of GSLs, our method accurately differentiates human glioma with/without isocitrate dehydrogenase genetic mutation, and normal brain tissue.


Assuntos
Encéfalo , Glioma , Glicoesfingolipídeos , Humanos , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/química , Glioma/metabolismo , Glioma/genética , Glioma/patologia , Encéfalo/metabolismo , Lipidômica/métodos , Espectrometria de Massas em Tandem/métodos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Cromatografia Líquida/métodos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Animais , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...