Naguib Mechawar
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View article: Protocol for antibody-based m6A sequencing of human postmortem brain tissues
Protocol for antibody-based m6A sequencing of human postmortem brain tissues Open
View article: A comprehensive characterization of the phospholipid and cholesterol composition of the uncinate fasciculus in the human brain: evidence of age-related alterations
A comprehensive characterization of the phospholipid and cholesterol composition of the uncinate fasciculus in the human brain: evidence of age-related alterations Open
The uncinate fasciculus (UF) is a long-range association fiber tract that serves to connect the anterior temporal lobe with the orbitofrontal cortex. The UF has been implicated via neuroimaging studies in the neurobiological vulnerability …
View article: Cerebellar astrocytic alterations in depression
Cerebellar astrocytic alterations in depression Open
Accumulating evidence suggests dysfunction of cerebellar-cerebral circuits in depression. However, the potential cellular and molecular alterations associated with depression in the cerebellum remain largely uncharacterized. While postmort…
View article: Ultrastructural Analysis of Human Uncinate Fasciculus with Spectral-Focusing Coherent Anti-Stokes Raman Spectroscopy
Ultrastructural Analysis of Human Uncinate Fasciculus with Spectral-Focusing Coherent Anti-Stokes Raman Spectroscopy Open
Characterizing the ultrastructure of myelin in the human brain is key to understanding the neurobiology of both health and disease. In postmortem human brain tissue, electron microscopy is often technically unfeasible due to poorer tissue …
View article: GPC5 expression highlights astrocytic heterogeneity and divergent hippocampal responses in Alzheimer’s and Parkinson’s Dementia
GPC5 expression highlights astrocytic heterogeneity and divergent hippocampal responses in Alzheimer’s and Parkinson’s Dementia Open
Astrocytes are central to central nervous system (CNS) homeostasis and memory consolidation. They also display remarkably heterogeneous morphological phenotypes, functions and molecular profiles between and within distinct regions of the h…
View article: Characterizing neuronal cell bodies in human postmortem cerebral white matter tracts
Characterizing neuronal cell bodies in human postmortem cerebral white matter tracts Open
Until the discovery of white matter neurons (WMN) in the 19th century, white matter (WM) was considered to be completely devoid of neuronal cell bodies. Despite evidence consistently showing evident neuronal soma within cortical WM and the…
View article: 603. CONVERGING HUMAN-SPECIFIC EVIDENCE IMPLICATES ASTROCYTIC GLUTAMATE REGULATION IN STRESS-RELATED PSYCHIATRIC DISORDERS
603. CONVERGING HUMAN-SPECIFIC EVIDENCE IMPLICATES ASTROCYTIC GLUTAMATE REGULATION IN STRESS-RELATED PSYCHIATRIC DISORDERS Open
Background Severe stress is the leading environmental risk factor for psychiatric disorders. Yet, we have a limited understanding of what underlies this association in humans. Astrocytes, an abundant non-neuronal cell type, are key regulat…
View article: Distribution and morphological features of astrocytes and Purkinje cells in the human cerebellum
Distribution and morphological features of astrocytes and Purkinje cells in the human cerebellum Open
Introduction The cerebellar cortex is now recognized as a functionally heterogeneous brain region involved not only in traditional motor functioning but also in higher-level emotional and cognitive processing. Similarly, cerebellar astrocy…
View article: A post-mortem investigation of the locus coeruleus-noradrenergic system in resilience to childhood abuse
A post-mortem investigation of the locus coeruleus-noradrenergic system in resilience to childhood abuse Open
Childhood abuse (CA) is one of the strongest lifetime predictors of major depressive disorder (MDD) and suicide. However, some individuals exposed to CA are resilient, avoiding the development of psychopathology. Recently, the locus coerul…
View article: Altered proteomics in brain extracellular vesicles from depressed individuals who died by suicide implicates synaptic processes
Altered proteomics in brain extracellular vesicles from depressed individuals who died by suicide implicates synaptic processes Open
Background Major depressive disorder (MDD) is a common and debilitating disorder whose molecular neurobiology remains unclear. Extracellular vesicles (EVs) are small vesicles that are released by cells and are involved in intercellular com…
View article: A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder
A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder Open
Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these omics and the contribution of individual cell type…
View article: Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex
Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex Open
Microglia, known for their diverse roles in the central nervous system, have recently been recognized for their involvement in degrading the extracellular matrix. Perineuronal nets (PNNs), a specialized form of this matrix, are crucial for…
View article: Microglia aggregates define distinct immune and neurodegenerative niches in Alzheimer's disease hippocampus.
Microglia aggregates define distinct immune and neurodegenerative niches in Alzheimer's disease hippocampus. Open
In Alzheimer's disease (AD), microglia show strong associations with amyloid-β (Aβ) and tau pathology, forming cellular aggregates such as Aβ plaque-associated microglia (PaM). Using high-content neuropathology, we found another type of mi…
View article: Altered m6A RNA methylation profiles in depression implicate the dysregulation of discrete cellular functions in males and females
Altered m6A RNA methylation profiles in depression implicate the dysregulation of discrete cellular functions in males and females Open
Adverse environmental stress represents a significant risk factor for major depressive disorder (MDD), often resulting in disrupted synaptic connectivity which is known to be partly regulated by epigenetic mechanisms. N6-methyla…
View article: Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain
Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain Open
Background Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spati…
View article: A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder
A multi-omics and cell type-specific characterization of the ventral striatum in human cocaine use disorder Open
Epigenome, transcriptome, and proteome analyses of postmortem brains have revealed initial molecular insights into cocaine use disorder (CUD). However, the inter-relationship between these –omics and the contribution of individual cell typ…
View article: Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder
Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder Open
View article: Pericytes modulate brain vascular integrity in social stress and depression
Pericytes modulate brain vascular integrity in social stress and depression Open
Major depressive disorder (MDD) is a leading cause of disease burden worldwide with low therapeutic efficacy. The blood-brain barrier (BBB) is essential to maintain brain homeostasis and regulate drug delivery. Chronic social stress, MDD’s…
View article: The Douglas-Bell Canada Brain Bank Post-mortem Brain Imaging Protocol
The Douglas-Bell Canada Brain Bank Post-mortem Brain Imaging Protocol Open
Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Post-mortem MRIs can provide complementary anatomical and micro…
View article: Human-specific features of cerebellar astrocytes and Purkinje cells: an anatomical comparison with mice and macaques
Human-specific features of cerebellar astrocytes and Purkinje cells: an anatomical comparison with mice and macaques Open
Little is known about the morphological diversity and distribution of cerebellar astrocytes in the human brain and how or if these features differ from those of cerebellar astrocytes in species used to model human illnesses. To address thi…
View article: Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse
Pervasive neurovascular dysfunction in the ventromedial prefrontal cortex of female depressed suicides with a history of childhood abuse Open
Exposure to early life adversity (ELA) poses a significant global public health concern, with profound pathophysiological implications for affected individuals. Studies suggest that ELA contributes to endothelial dysfunction, bringing into…
View article: Astrocytic glutamate regulation is shaped by adversity and glucocorticoid signalling
Astrocytic glutamate regulation is shaped by adversity and glucocorticoid signalling Open
Astrocytes are a brain cell type vulnerable to the effects of stress and the development of psychiatric-like phenotypes in animals, yet how this translates to humans is unclear. Here, we probed the diversity of ∼145,000 total human cortica…
View article: Astrocytic Cannabinoid Receptor 1 Promotes Resilience by Dampening Stress-Induced Blood-Brain Barrier Alterations and Inflammation
Astrocytic Cannabinoid Receptor 1 Promotes Resilience by Dampening Stress-Induced Blood-Brain Barrier Alterations and Inflammation Open
View article: MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study
MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study Open
View article: Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use
Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use Open
A novel radiotracer, [11C]SL25.1188 targets monoamine oxidase-B (MAO-B) enzyme, which metabolizes monoamines (including dopamine) primarily found in astrocytes. Altered astrocyte function in schizophrenia is supported by converg…
View article: Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex
Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex Open
Microglia, known for their diverse roles in the central nervous system, have recently been recognized for their involvement in degrading the extracellular matrix. Perineuronal nets (PNNs), a specialized form of this matrix, are crucial for…
View article: The Douglas Bell Canada Brain Bank Post-mortem Brain Imaging Protocol
The Douglas Bell Canada Brain Bank Post-mortem Brain Imaging Protocol Open
Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Postmortem MRIs can provide complementary anatomical and micros…
View article: Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain
Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain Open
Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family tha…
View article: Preclinical validation of the efficacy of TRPC4/5 inhibition for reduction of excessive aversion processing: neurobehavioral evidence
Preclinical validation of the efficacy of TRPC4/5 inhibition for reduction of excessive aversion processing: neurobehavioral evidence Open
View article: Stress-induced alterations of miRNAs across human and mouse limbic brain areas
Stress-induced alterations of miRNAs across human and mouse limbic brain areas Open