# Acetate and propionate vs. iTBS as a novel method for cognitive dysfunction and anxiety symptoms in delayed encephalopathy after acute carbon monoxide poisoning rat

**Authors:** Tianyu Meng, Xin Zhang, Jili Zhao, Hui Xue, Lehua Yu

PMC · DOI: 10.3389/fphar.2025.1520988 · 2025-02-26

## TL;DR

This study compares the effectiveness of intermittent theta burst stimulation and short-chain fatty acids in treating cognitive and anxiety symptoms in rats with delayed encephalopathy after carbon monoxide poisoning.

## Contribution

The study introduces a novel comparison of iTBS and SCFAs (acetate and propionate) for treating DEACMP symptoms.

## Key findings

- Both iTBS and SCFAs significantly improved cognitive dysfunction and anxiety symptoms in DEACMP rats.
- SCFAs also improved decreased levels of GPR41, GPR43, dopamine, and norepinephrine in the hippocampus.
- The acetate/propionate–GPR41/GPR43–IL-1β/IL-6/TNF-α–dopamine/norepinephrine pathway may be a potential treatment mechanism for DEACMP.

## Abstract

The optimal treatment methods for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) were not identified. Thus, this study was conducted to compare the efficacies of intermittent theta burst stimulation (iTBS) and short-chain fatty acids (SCFAs) in treating cognitive dysfunction and anxiety symptoms of DEACMP rat.

In phase I, a DEACMP rat model was built to assess the inflammation levels in the hippocampus and levels of SCFAs in the serum of DEACMP rats. In phase II, DEACMP rats were randomly assigned into four groups: DEACMP + placebo, DEACMP + SCFAs, DEACMP + sham iTBS, and DEACMP + iTBS. The intervention was continued for 2 weeks. A Morris water maze and open field tests were used to assess cognitive function and anxiety symptoms, respectively.

The levels of three inflammatory factors (IL-1β, IL-6, and TNF-α) and two SCFAs (acetate and propionate) were significantly increased and decreased, respectively, in DEACMP rats. After treatment, cognitive dysfunction and anxiety symptoms were significantly improved in the DEACMP + iTBS group and the DEACMP + SCFAs (consisting of acetate and propionate) group. Both SCFAs and iTBS could significantly improve the increased levels of IL-1β, IL-6, and TNF-α in the hippocampus, and SCFAs could also improve the decreased levels of GPR41, GPR43, dopamine, and norepinephrine in the hippocampus of DEACMP rats.

These results indicate that both iTBS and SCFA solutions consisting of acetate and propionate produced good effects on DEACMP rats by regulating inflammation levels in the hippocampus, and acetate/propionate–GPR41/GPR43–IL-1β/IL-6/TNF-α–dopamine/norepinephrine may be a potential pathway in SCFAs for the treatment of DEACMP.

## Linked entities

- **Proteins:** FFAR3 (free fatty acid receptor 3), FFAR2 (free fatty acid receptor 2), IL1B (interleukin 1 beta), IL6 (interleukin 6), TNF (tumor necrosis factor)
- **Chemicals:** acetate (PubChem CID 175), propionate (PubChem CID 104745), carbon monoxide (PubChem CID 281)
- **Diseases:** delayed encephalopathy after acute carbon monoxide poisoning (MONDO:0005493)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Ffar2 (free fatty acid receptor 2) [NCBI Gene 292794] {aka Gpr43}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Ffar3 (free fatty acid receptor 3) [NCBI Gene 365228] {aka Gpr41}
- **Diseases:** acute (MESH:D000208), inflammation (MESH:D007249), encephalopathy (MESH:D001927), cognitive dysfunction (MESH:D003072), anxiety (MESH:D001007)
- **Chemicals:** Acetate (MESH:D000085), norepinephrine (MESH:D009638), SCFA (MESH:D005232), DEACMP (-), propionate (MESH:D011422), dopamine (MESH:D004298)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11897562/full.md

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Source: https://tomesphere.com/paper/PMC11897562