Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease

The mechanism by which neurogenesis regulates the profile of neurons and glia in the hippocampal formation is not known. Further, the effect of neurogenesis on neuronal vulnerability characterizing the entorhinal cortex in Alzheimer's disease (AD) is unknown. Here, we used in situ sequencing to...

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Main Authors: Zachery D. Morrissey, Pavan Kumar, Trongha X. Phan, Mark Maienschein-Cline, Alex Leow, Orly Lazarov
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Dementia
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Online Access:https://www.frontiersin.org/articles/10.3389/frdem.2025.1546433/full
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author Zachery D. Morrissey
Zachery D. Morrissey
Zachery D. Morrissey
Pavan Kumar
Trongha X. Phan
Mark Maienschein-Cline
Alex Leow
Alex Leow
Orly Lazarov
author_facet Zachery D. Morrissey
Zachery D. Morrissey
Zachery D. Morrissey
Pavan Kumar
Trongha X. Phan
Mark Maienschein-Cline
Alex Leow
Alex Leow
Orly Lazarov
author_sort Zachery D. Morrissey
collection DOAJ
description The mechanism by which neurogenesis regulates the profile of neurons and glia in the hippocampal formation is not known. Further, the effect of neurogenesis on neuronal vulnerability characterizing the entorhinal cortex in Alzheimer's disease (AD) is unknown. Here, we used in situ sequencing to investigate the spatial transcription profile of neurons and glia in the hippocampal circuitry in wild-type mice and in familial AD (FAD) mice expressing varying levels of neurogenesis. This approach revealed that in addition to the dentate gyrus, neurogenesis modulates the cellular profile in the entorhinal cortex and CA regions of the hippocampus. Notably, enhancing neurogenesis in FAD mice led to partial restoration of neuronal and cellular profile in these brain areas, resembling the profile of their wild-type counterparts. This approach provides a platform for the examination of the cellular dynamics in the hippocampal formation in health and in AD.
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spelling doaj-art-fa13ca121a154c49b20188c3bf5e16c62025-08-20T02:17:34ZengFrontiers Media S.A.Frontiers in Dementia2813-39192025-04-01410.3389/frdem.2025.15464331546433Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's diseaseZachery D. Morrissey0Zachery D. Morrissey1Zachery D. Morrissey2Pavan Kumar3Trongha X. Phan4Mark Maienschein-Cline5Alex Leow6Alex Leow7Orly Lazarov8Graduate Program in Neuroscience, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Psychiatry, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL, United StatesResearch Informatics Core, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Psychiatry, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Biomedical Engineering, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL, United StatesThe mechanism by which neurogenesis regulates the profile of neurons and glia in the hippocampal formation is not known. Further, the effect of neurogenesis on neuronal vulnerability characterizing the entorhinal cortex in Alzheimer's disease (AD) is unknown. Here, we used in situ sequencing to investigate the spatial transcription profile of neurons and glia in the hippocampal circuitry in wild-type mice and in familial AD (FAD) mice expressing varying levels of neurogenesis. This approach revealed that in addition to the dentate gyrus, neurogenesis modulates the cellular profile in the entorhinal cortex and CA regions of the hippocampus. Notably, enhancing neurogenesis in FAD mice led to partial restoration of neuronal and cellular profile in these brain areas, resembling the profile of their wild-type counterparts. This approach provides a platform for the examination of the cellular dynamics in the hippocampal formation in health and in AD.https://www.frontiersin.org/articles/10.3389/frdem.2025.1546433/fullAlzheimer's diseaseneurogenesisspatial transcriptomicshippocampusadult hippocampal neurogenesis
spellingShingle Zachery D. Morrissey
Zachery D. Morrissey
Zachery D. Morrissey
Pavan Kumar
Trongha X. Phan
Mark Maienschein-Cline
Alex Leow
Alex Leow
Orly Lazarov
Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
Frontiers in Dementia
Alzheimer's disease
neurogenesis
spatial transcriptomics
hippocampus
adult hippocampal neurogenesis
title Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
title_full Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
title_fullStr Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
title_full_unstemmed Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
title_short Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
title_sort neurogenesis drives hippocampal formation wide spatial transcription alterations in health and alzheimer s disease
topic Alzheimer's disease
neurogenesis
spatial transcriptomics
hippocampus
adult hippocampal neurogenesis
url https://www.frontiersin.org/articles/10.3389/frdem.2025.1546433/full
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