# Alternative splicing mechanism in stress.

> **NIH NIH R21** · UPSTATE MEDICAL UNIVERSITY · 2021 · $202,500

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal represents a highly innovative line of research focusing on the role of pre-mRNA splicing in
the pathophysiology of chronic stress. Chronic stress is a major risk factor for many neuropsychiatric
disorders, including major depressive disorder, anxiety disorder, post-traumatic stress disorder (PTSD),
schizophrenia, and addiction. Neurotransmission and synaptic plasticity are known to be dysregulated by
chronic stress, leading to long-term neuronal dysfunction and altered emotional and cognitive behaviors.
We have novel data showing the dysregulation of splicing factors in the brains of chronically stressed
animals. Furthermore, our findings indicate a role for upstream regulatory splicing factors in mediating
synaptic function. Dysregulation of pre-mRNA splicing events can lead to neuronal dysfunction due to
aberrant protein expression levels and expression of protein isoforms with altered functions. Therefore,
we propose to investigate a regulatory pre-mRNA splicing mechanism for the neuronal dysfunction arising
from chronic stress. We will do so using animal and cellular models to determine the precise roles of pre-
mRNA splicing elements in neuronal function and behavior, and to elucidate how they are dysregulated in
chronic stress. We expect results from the proposed studies to provide novel insights into the cellular and
molecular mechanisms underlying stress-induced neuropathology and behavior, and to identify potential
candidates for future translational therapeutic strategies for stress-related neuropsychiatric disorders and
addiction. The studies proposed in this application will provide a strong foundation for furthering our
understanding of how pre-RNA splicing events maintain the functional integrity of the CNS as it responds
to chronic stress and will inform future stress-related translational studies in major depressive disorder,
anxiety disorder, PTSD, schizophrenia, and addiction.

## Key facts

- **NIH application ID:** 10196155
- **Project number:** 1R21MH126405-01
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Julio Licinio
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $202,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196155

## Citation

> US National Institutes of Health, RePORTER application 10196155, Alternative splicing mechanism in stress. (1R21MH126405-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10196155. Licensed CC0.

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