Transcriptome Profiles Associated With Resilience and Susceptibility to Single Prolonged Stress in the Locus Coeruleus and Nucleus Accumbens in Male Sprague-Dawley Rats

Authors

Roxanna J. Nahvi, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States.
Arax Tanelian, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States.
Chiso Nwokafor, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States.
Arthur Godino, Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Eric Parise, Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Molly Estill, Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Li Shen, Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Eric J. Nestler, Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Esther L. Sabban, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, United States. Electronic address: sabban@nymc.edu.Follow

Author Type(s)

Faculty

DOI

10.1016/j.bbr.2022.114162

Journal Title

Behavioural Brain Research

First Page

114162

Document Type

Article

Publication Date

2-15-2023

Department

Biochemistry and Molecular Biology

Abstract

Although most people are subjected to traumatic stress at least once in their lifetime, only a subset develop long-lasting, stress-triggered neuropsychiatric disorders, such as PTSD. Here we examined different transcriptome profiles within the locus coeruleus (LC) and nucleus accumbens (NAc) that may contribute to stress susceptibility. Sprague Dawley male rats were exposed to the single prolonged stress (SPS) model for PTSD. Two weeks later they were tested for their anxiety/avoidance behavior on the Elevated Plus Maze (EPM) and were divided into high and low anxiety-like subgroups. RNA (n = 5 per group) was subsequently isolated from LC and NAc and subjected to RNAseq. Transcriptome analysis was used to identify differentially-expressed genes (DEGs) which differed by at least 50 % with significance of 0.01. The LC had more than six times the number of DEGs than the NAc. Only one DEG was regulated similarly in both locations. Many of the DEGs in the LC were associated with morphological changes, including regulation of actin cytoskeleton, growth factor activity, regulation of cell size, brain development and memory, with KEGG pathway of regulation of actin cytoskeleton. The DEGs in the NAc were primarily related to DNA repair and synthesis, and differential regulation of cytokine production. The analysis identified MTPN (myotrophin) and NR3C1 (glucocorticoid receptor) as important upstream regulators of stress susceptibility in the LC. Overall the study provides new insight into molecular pathways in the LC and NAc that are associated with anxiety-like behavior triggered by stress susceptibility or resilience.

Recommended Citation

Nahvi, R. J., Tanelian, A., Nwokafor, C., Godino, A., Parise, E., Estill, M., Shen, L., Nestler, E. J., & Sabban, E. L. (2023). Transcriptome Profiles Associated With Resilience and Susceptibility to Single Prolonged Stress in the Locus Coeruleus and Nucleus Accumbens in Male Sprague-Dawley Rats. Behavioural Brain Research, 439, 114162. https://doi.org/10.1016/j.bbr.2022.114162