Biomedical subjects

Pallavi P Gopal

Publications and source records attributed to Pallavi P Gopal.

3 recordsLinked to original sources

PubMed2026

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type, and sex specificity of gene expression with novel genetic risk for MERTK in female.

BackgroundAlzheimer's disease (AD), the most common age-related neurodegenerative disease, is closely associated with both amyloid-β plaque and neuroinflammation. Two thirds of AD patients are female, and they have a higher disease risk; women with AD have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration.ObjectiveThis study aimed to determine how sex difference induces structural brain changes and molecular cell vulnerabilities in AD, with a focus on identifying sex-specific transcriptional alterations and genetic risk factors.MethodsWe performed single nucleus RNA sequencing on postmortem brains from individuals with AD and age- and sex-matched controls, focusing on the middle temporal gyrus, a cortical brain region strongly affected by the disease, and integrated single nucleus RNA sequencing results with genome-wide association study (GWAS) data using cell type-specific enrichment and generalized gene-set analysis approaches. The analysis pipeline is provided with threshold information.ResultsWe identified a selectively vulnerable subpopulation of layer 2/3 excitatory neurons that were RORB-negative and CDH9-expressing in both males and females. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of AD brains differed between males and females. Integrating single cell transcriptomic data with results from GWAS, we identified MERTK genetic variation as a candidate novel risk factor for AD selectively in females.ConclusionsTaken together, our single cell atlas of middle temporal gyrus revealed a unique cellular-level view of sex-specific transcriptional changes in AD, illuminating GWAS identification of sex-specific AD genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of AD.

Alzheimer's disease↗

PubMed2023

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type and sex specificity of gene expression with novel genetic risk for MERTK in female.

Alzheimer's disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer's disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer's disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer's disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identified MERTK genetic variation as a risk factor for Alzheimer's disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer's disease, illuminating GWAS identification of sex-specific Alzheimer's risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer's disease.

Journal Article↗

PubMed2004

Axon mediated interneuron migration.

Mammalian forebrain development requires extensive cell migration for cells to reach their appropriate location in the adult brain. Defects in this migration result in human malformations and neurologic deficits. Thus, understanding the mechanisms underlying normal cell migration during development is essential to understanding the pathogenesis of human malformations. Radial glia are known to support radial cell migration, while axons have been proposed as substrate for some non-radially migrating cells. Herein we have directly tested the hypothesis that axons can support non-radial cell migration. One population of cells known to migrate non-radially is the inhibitory interneurons that move from the ganglionic eminence to the cerebral cortex. We first show that early born GABAergic cells colocalize with TAG-1-positive (TAG-1+) axons, while later born cells colocalize with intermediate weight neurofilament-positive, TAG-1-negative (TAG-1-) processes, suggesting temporal differences in substrate specificities. We next developed an in vitro assay that allows us to observe cell migration on axons in culture. Using this assay we find that early born medial ganglionic eminence-derived interneurons migrate preferentially on TAG-1+ axons, while later born cells only migrate on neurofilament-positive/TAG-1- processes. These data provide the first direct evidence that ganglionic eminence cells migrate on axons and that there is an age-dependent substrate preference. Furthermore, the assay developed and characterized herein provides a robust method to further study the molecular substrates and guidance cues of axonophilic cell migration in neural development.

Aging↗