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. 2025 May;62(5):5758-5773.
doi: 10.1007/s12035-024-04641-3. Epub 2024 Dec 2.

[1H-13C]-NMR-Based Metabolic Kinetics Reveals Brain Neurochemical Alterations in Mice After Retinal Ischemia-Reperfusion Injury

Guojing Lu #  1 , Rong Huang  1 , Siyu Zeng  1 , Yiqiao Xing  1 , Hang Xie  1 , Lei Du #  2
Affiliations

[1H-13C]-NMR-Based Metabolic Kinetics Reveals Brain Neurochemical Alterations in Mice After Retinal Ischemia-Reperfusion Injury

Guojing Lu et al. Mol Neurobiol. 2025 May.

Abstract

Retinal ischemia-reperfusion injury (RIRI) is a pathological process that occurs in various blinding eye diseases and is often accompanied by anxiety and depression. However, the underlying metabolic mechanism of mood disorders remains unclear. This study aimed to investigate the metabolic dynamics of the brain after RIRI. C57BL/6 J mice were used to establish the RIRI model and assessed after 1 and 7 days. Mood-related behaviors were examined using open-field, elevated plus-maze, and forced swimming tests. Retinal injury histology was assessed using retinal hematoxylin and eosin staining. Retinal apoptosis was measured via the TdT-mediated dUTP nick-end labeling staining. The 13C-labeled metabolite information for six brain regions of interest was obtained using the [1H-13C]-NMR technique. Retinal tissue damage and cell apoptosis in the retina were observed 1 and 7 days after RIRI. One day after RIRI, mice displayed anxiety- and depression-like behaviors, and multiple metabolites involved in the glutamine (Gln)/glutamate (Glu)-γ-aminobutyric acid (GABA) and tricarboxylic acid (TCA) cycles exhibited reductions in all studied brain regions, with frontal cortex (FC) and temporal cortex (TC) being the most markedly altered. Metabolites and behavioral indicators nearly returned to normal after 7 days. Significant positive correlations between Gln/Glu-GABA and TCA cycle metabolites were observed in the RIRI brain. The results revealed that within a short period after RIRI, there was a reduction in brain metabolites and a disruption of the Gln/Glu-GABA and TCA cycles, which may contribute to mood disorders in mice.

Keywords: Eye-brain connection; Gln/Glu-GABA cycle; Mood disorders; Retinal ischemia-reperfusion injury; [1H-13C]-NMR.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: This study was performed in line with the principles of the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Approval was granted by the Ethics Committee of the Renmin Hospital of Wuhan University. Consent for Publication: All authors have given their consent to publish this article. Competing Interests: The authors declare no competing interests.

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