Ex-vivo Imaging of Glial Energy Metabolism in the Neonatal Mouse Brain during Convulsive Seizures with Intranasal Radiotracer Administration.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-03-25 DOI:10.1007/s11307-025-02000-9

Rie Hosoi, Kenya Tada, Takahiro Hayakawa, Yuka Haga

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引用次数: 0

Abstract

Purpose: In this study, we examined changes in glial energy metabolism in neonatal mouse brain images obtained under pathological conditions following intranasal administration of the radiotracer [2-¹⁴C]acetate.

Procedures: [2-¹⁴C]acetate was administered via the mouse nasal cavity, after which autoradiograms of the brain of 7-day-old mice were obtained. Radio thin-layer chromatography was applied for metabolite analysis of brain radioactivity. We also compared brain uptake of [2-¹⁴C]acetate when administrated intranasally and intravenously in 3-week-old mice. To confirm selective uptake by glial cells, [2-¹⁴C]acetate was injected into the nasal cavity of mice injected with a glial toxin in the brain. Pentylenetetrazole (PTZ) was applied to induce seizures.

Results: Intranasally administered [2-¹⁴C]acetate was rapidly incorporated into the brains of 7-day-old mice, reaching its highest uptake level 20 min after administration. After 20 min of intranasal [2-¹⁴C]acetate administration, glutamate and glutamine accounted for 32 ± 2.5% and 30 ± 3.4% of total brain radioactivity, respectively. There was no difference in the radioactivity distribution in the brain between intranasal and intravenous administration, except in the ventral olfactory bulb in 3-week-old mice. Microinjection of the glial-specific toxin fluorocitrate reduced the accumulation of radioactivity in the brain by 60% following intranasal administration in 3-week-old mice. The uptake of [2-¹⁴C]acetate in the brains of 7-day-old mice significantly decreased 30 min after systemic PTZ administration, suggesting a decrease in energy metabolism in glial cells during seizures.

Conclusions: Quantitative images of biological functions in the neonatal mouse brain can be obtained by intranasal administration. This technique allowed the observation of a decrease in acetate uptake associated with convulsive seizures. The results of this study could be applied to the imaging of biological brain functions and research on neurological disorders using labeled probes in neonatal mice.

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.