# Deciphering Molecular Mechanisms of Post-Stroke Depression in Aged Mice

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $700,817

## Abstract

PROJECT SUMMARY
Stroke is the leading cause of adult disability. Over the last 20 years, with the decline in stroke mortality due to
improvements in acute care, there has been an increase in the global stroke burden. Most stroke survivors
experience varying degrees of motor and neuropsychiatric disorders that significantly impair their quality of life.
Post stroke depression (PSD) is a common and serious consequence of stroke that affects many stroke
survivors. Women are twice as likely to develop depression after stroke compared to men. Affected individuals
are at an increased risk of mortality, recurrent stroke and have delayed functional recovery. Immune
dysregulation, microglial hyper-activation, enhanced inflammation, and decreased levels of neurogenesis have
been implicated in the pathophysiology of both depression and impaired stroke recovery. These alterations are
even more pronounced in aged individuals. This proposal will focus on elucidating the mechanisms underlying
the development of depression in aged mice after an ischemic stroke.
Oxytocin (OXT) is a neuropeptide that acts as both a hormone and neurotransmitter and is an important regulator
of social behavior, learning and memory, maintenance of cardiovascular health. Based on our preliminary
studies, and literature, taurine regulates the release of OXT and reduces neuro-inflammation. Taurine is a highly
abundant free amino acid in the brain, with multiple functions including a vital role as a neurotransmitter and is
capable of reversing stress-induced depressive-behaviors. Interestingly, both OXT and taurine effectively reduce
microglial activation, and this raises the intriguing possibility that both are involved in the development of PSD
through the modulation of microglia. In this context, we hypothesize that stroke leads to a loss of taurine and
OXT with subsequent increase in microglial activation and development of PSD. In our preliminary studies, we
have found that taurine and oxytocin levels decline with stroke in both mice and humans. We have also found
that chronic oxytocin inhibition leads to depressive-like behaviors in young animals even without brain injury, and
inhibition of oxytocin significantly impairs post-stroke recovery. By using wild-type and knockout mice, a variety
of pharmacological tools, cell-specific genetic models, and bone marrow chimeras, we will manipulate oxytocin
signaling (Aim 1); supplement taurine (Aim 2), and deplete microglia (Aim 3), to determine if these mechanisms
are involved in the development of PSD phenotypes in aged mice of both sexes. We will determine the potential
of taurine and oxytocin to improve recovery in aged mice after stroke. The results from this study have a high
potential for translation into clinical settings, as oxytocin and taurine are in clinical use for other indications.

## Key facts

- **NIH application ID:** 10945546
- **Project number:** 1R01AG088518-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Antonio Lucio Teixeira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,817
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945546

## Citation

> US National Institutes of Health, RePORTER application 10945546, Deciphering Molecular Mechanisms of Post-Stroke Depression in Aged Mice (1R01AG088518-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10945546. Licensed CC0.

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