Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice

Maya M Evans; Benjamin W Q Hing; Matthew A Weber; Sara V Maurer; Ahmed I Baig; Grace S Kim; Samantha L Anema; Rhett M Ellerbroek; Kartik Sivakumar; Jacob J Michaelson; Nandakumar S Narayanan; Hanna E Stevens

doi:10.1101/2024.12.27.627207

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Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice

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Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice

Maya M Evans, Benjamin W Q Hing, Matthew A Weber, Sara V Maurer, Ahmed I Baig, Grace S Kim, Samantha L Anema, Rhett M Ellerbroek, Kartik Sivakumar, Jacob J Michaelson, …

bioRxiv

Cold Spring Harbor Laboratory

12/27/2024

DOI: 10.1101/2024.12.27.627207

PMCID: PMC11703269

PMID: 39763907

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https://doi.org/10.1101/2024.12.27.627207View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.

Stress

Pregnancy

Neurophysiology

Autism

neurodevelopment

striatum

single-cell

prenatal stress

autism spectrum disorder

neurodevelopmental disorders

Details

Title: Subtitle: Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice
Creators: Maya M Evans - University of Iowa
Benjamin W Q Hing - Iowa Neuroscience Institute, Iowa City, IA, 52242, USA
Matthew A Weber - University of Iowa
Sara V Maurer - Iowa Neuroscience Institute, Iowa City, IA, 52242, USA
Ahmed I Baig - Iowa Neuroscience Institute, Iowa City, IA, 52242, USA
Grace S Kim - University of Iowa
Samantha L Anema - University of Iowa
Rhett M Ellerbroek - University of Iowa
Kartik Sivakumar - University of Iowa
Jacob J Michaelson - University of Iowa
Nandakumar S Narayanan - University of Iowa
Hanna E Stevens - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2024.12.27.627207
PMID: 39763907
PMCID: PMC11703269
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Grant note: F31 MH131259 / NIMH NIH HHS T32 MH019113 / NIMH NIH HHS R01 MH122485 / NIMH NIH HHS
Language: English
Date posted: 12/27/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984772278002771

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