Genetic and Molecular Correlates of Cortical Thickness Alterations in Adults with Obsessive-Compulsive Disorder: A Transcription-Neuroimaging Association Analysis DOI Creative Commons
Xiao Hu, Da Zhang,

Chang Teng

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 3, 2024

Abstract Although numerous neuroimaging studies have shown neural alterations in individuals with obsessive-compulsive disorder (OCD), a psychiatric characterised by intrusive cognitions and repetitive behaviours, the molecular mechanisms linking brain structural changes gene expression remain poorly understood. By combining Allen Human Brain Atlas dataset data from Meta-Analysis (ENIGMA) consortium independent cohorts, this study performed partial least squares regression enrichment analysis to probe correlation between transcription cortical thickness variation adults OCD. The map of case–control differences was spatially correlated weighted combination genes enriched for neurobiologically relevant ontology terms, preferentially expressed across different cell types layers. These were specifically tissue, spanning nearly all developmental stages. Protein-protein interaction revealed that these coded network proteins encompassing several highly interactive hubs. findings bridge gap structure transcriptome OCD, fostering an integrative understanding potential biological mechanisms.

Language: Английский

Rare copy number variants reveal critical cell types and periods of brain development in neurodevelopmental disorders DOI Creative Commons
Susmita Malwade, Carl M. Sellgren, Navneet A. Vasistha

et al.

Biological Psychiatry Global Open Science, Journal Year: 2025, Volume and Issue: unknown, P. 100495 - 100495

Published: April 1, 2025

Language: Английский

Citations

0
High-throughput machine learning framework for predicting neurite deterioration using MetaFormer attention DOI Creative Commons
Kuanren Qian,

Genesis Omana Suarez,

Toshihiko Nambara

et al.

Computer Methods in Applied Mechanics and Engineering, Journal Year: 2025, Volume and Issue: 442, P. 118003 - 118003

Published: April 24, 2025

Language: Английский

Citations

0
A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies DOI Creative Commons

Ogochukwu J. Uweru,

Akhabue K. Okojie,

Aparna Trivedi

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: April 15, 2024

Abstract Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature microglial-neuronal interactions, but seldom consider how dynamism varies with microglial sex differences, leaving a significant gap our knowledge. This study focuses on P2RY12, highly expressed signature gene that mediates we show adult females significantly higher expression receptor than male microglia. We further demonstrate genetic deletion P2RY12 induces sex-specific cellular perturbations microglia and neurons more affected. Correspondingly, female mice lacking exhibit unique behavioral anomalies not observed counterparts. These findings underscore critical, roles offering new insights into basal interactions potential implications for CNS disease mechanisms. Graphical

Language: Английский

Citations

3
Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability DOI Creative Commons

K. C. Rajan,

Alina S. Tiemroth,

Abbigail N. Thurmon

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: April 15, 2024

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental genetic. Neuropsychiatric conditions such autism spectrum (ASD), intellectual disability (ID), attention deficit hyperactivity (ADHD) common NDDs characterized by their hereditary underpinnings inherent heterogeneity. Genetic risk factors for increasingly being identified non-coding regions proteins bound to them, including transcriptional regulators chromatin remodelers. Importantly, de novo mutations emerging important contributors neuropsychiatric disorders. Recently, co-factor Zmiz1 or its regulatory have been unrelated patients syndromic ID ASD. However, the role development is unknown. Here, using publicly available databases mutant mouse model, we reveal that highly expressed during embryonic mice humans, though broadly across brain, enriched areas prominently impacted ASD cortex, hippocampus, cerebellum. We investigated relationship between structure pathogenicity protein variants, epigenetic marks associated regulation, interactions signaling pathways regulated Zmiz1. Our analysis reveals regulates multiple developmental processes, neurogenesis, neuron connectivity, synaptic signaling. This work paves way future studies on functions highlights importance combining models human data.

Language: Английский

Citations

3
Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design DOI

Abdul Wadood Nadeem,

Poonam Sharma, Pramod Gupta

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116964 - 116964

Published: May 1, 2025

Language: Английский

Citations

0
Mechanisms of copy number variants in neuropsychiatric disorders: From genes to therapeutics DOI Creative Commons
Marc P. Forrest, Peter Penzes

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 82, P. 102750 - 102750

Published: July 27, 2023

Language: Английский

Citations

9
A Systematic Review of Air Pollution Exposure and Brain Structure and Function during Development DOI Creative Commons

Jessica Morrel,

Michelle Dong,

Michael A. Rosario

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

Air pollutants are known neurotoxicants. In this updated systematic review, we evaluate new evidence since our 2019 review on the effect of outdoor air pollution exposure childhood and adolescent brain structure function as measured by magnetic resonance imaging (MRI).

Language: Английский

Citations

2
A single-cell transcriptomic atlas of the prefrontal cortex across the human lifespan DOI Creative Commons
Hui Yang, Tereza Clarence, Madeline R. Scott

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Abstract The dorsolateral prefrontal cortex is central to higher cognitive functions and particularly vulnerable age-related decline. To advance our understanding of the molecular mechanisms underlying brain development, maturation, aging, we constructed a detailed single-cell transcriptomic atlas human cortex, encompassing over 1.3 million nuclei from 284 postmortem samples spanning full lifespan (0-97 years). This reveals distinct phases activity: dynamic developmental period, stabilization during midlife, subtle yet coordinated changes in late adulthood. Modeling non-linear age trends across shows ten trajectories entire transcriptome all cell types, with notable findings neurons microglia, linked neurodevelopmental disorders Alzheimer’s disease risk, respectively. Moreover, excitatory exhibit convergence gene expression patterns lifespan, suggesting emergence common signature aging. Pseudotime analysis tracing progression cellular lineages throughout life key clusters that reflect as well their connection brain-related diseases. We uncover significant circadian rhythm reprogramming adulthood, characterized by disruption core clock rhythmicity new rhythmic patterns, within microglia oligodendrocytes. comprehensive provides baseline for transitions development through successful aging cortex.

Language: Английский

Citations

2
Drug targeting in psychiatric disorders — how to overcome the loss in translation? DOI
Konstantin Khodosevich, Katarina Dragičević, Oliver Howes

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(3), P. 218 - 231

Published: Dec. 19, 2023

Language: Английский

Citations

6
epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains DOI Creative Commons
Josephine K. Liwang,

Fae A. Kronman,

Jennifer A. Minteer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 25, 2023

Abstract During development, brain regions follow encoded growth trajectories. Compared to classical charts, high-definition charts could quantify regional volumetric and constituent cell types, improving our understanding of typical pathological development. Here, we create high-resolution 3D atlases the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at days (P) 4, 6, 8, 10, 12, 14, determine different regions. We utilize 11 type-specific transgenic animals validate refine labels. Moreover, reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic), cortical layer-specific microglia as key players shaping find contrasting GABAergic neuronal densities between striatal areas, stabilizing P12. somatostatin-expressing interneurons undergo regionally distinct reductions, while vasoactive intestinal peptide-expressing show no significant changes. Remarkably, transition from high white matter tracks gray P10, selective increases sensory processing areas that correlate with emergence individual modalities. Lastly, an open-access web-visualization ( https://kimlab.io/brain-map/epDevAtlas ) for cell-type developmental all time points.

Language: Английский

Citations

4