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Inflammatory Milieu Induces Mitochondrial Alterations and Neuronal Activations in Hypothalamic POMC Neurons in a Time-Dependent Manner

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Abstract

Inflammation has been associated with numerous neurological disorders. Inflammatory environments trigger a series of cellular and physiological alterations in the brain. However, how inflammatory milieu affects neuronal physiology and how neuronal alterations progress in the inflammatory environments are not fully understood. In this study, we examined the effects of pro-inflammatory milieu on mitochondrial functions and neuronal activities in the hypothalamic POMC neurons. Treating mHypoA-POMC/GFP1 with the conditioned medium collected from LPS activated macrophage were employed to mimic the inflammatory milieu during hypothalamic inflammation. After a 24-h treatment, intracellular ROS/RNS levels were elevated, and the antioxidant enzymes were reduced. Mitochondrial respiration and mitochondrial functions, including basal respiratory rate, spared respiration capacity, and maximal respiration, were all significantly compromised by inflammatory milieu. Moreover, pro-inflammatory cytokines altered mitochondrial dynamics in a time-dependent manner, resulting in the elongation of mitochondria in POMC neurons after a 24-h treatment. Additionally, the increase of C-Fos and Pomc genes expression indicated that the neurons were activated upon the stimulation of inflammatory environment. This neuronal activation of were confirmed on the LPS-challenged mice. Collectively, a short-term to midterm exposure to inflammatory milieu stimulated metabolic switch and neuronal activation, whereas chronic exposure triggered the elevation of oxidative stress, the decrease of the mitochondrial respiration, and the alterations of mitochondrial dynamics.

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Data Availability

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge Mr. Clement Lee for his excellent technical support for TEM at Taipei Medical University Core Facility.

Funding

This work was supported by the Ministry of Science and Technology, Taiwan (MOST 106–2320-B-004–001).

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Authors and Affiliations

  1. Institute of Neuroscience, National ChengChi University, No. 64, Sec. 2, Zhinan Rd., Wenshan District, 11605, Taipei, Taiwan

    Yi-Chun Liao, Yeou San Lim, Pei-Wen Chu & Shau-Kwaun Chen

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Contributions

YCL, YSL, and PWC performed the experiments, analyzed data, prepared figures, and participated in manuscript writing; SKC designed experiments, integrated data, supervised, and wrote and reviewed the manuscript. All authors approved the final submission.

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Correspondence to Shau-Kwaun Chen.

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All animal protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of National Chengchi University. All of the animal experiments were performed in compliance with the IACUC regulations and Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines.

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Liao, YC., Lim, Y., Chu, PW. et al. Inflammatory Milieu Induces Mitochondrial Alterations and Neuronal Activations in Hypothalamic POMC Neurons in a Time-Dependent Manner. Mol Neurobiol 60, 1164–1178 (2023). https://doi.org/10.1007/s12035-022-03128-3

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