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Mitochondrial dysfunction and type I interferon signaling induce anxiodepressive-like behaviors in mice with neuropathic pain.
- Source :
-
Experimental neurology [Exp Neurol] 2023 Sep; Vol. 367, pp. 114470. Date of Electronic Publication: 2023 Jun 15. - Publication Year :
- 2023
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Abstract
- Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain; however, the cellular basis for chronic pain-mediated major depression remains unclear. Mitochondrial dysfunction induces neuroinflammation and has been implicated in various neurological diseases, including depression. Nevertheless, the relationship between mitochondrial dysfunction and anxiodepressive-like behaviors in the neuropathic pain state remains unclear. The current study examined whether hippocampal mitochondrial dysfunction and downstream neuroinflammation are involved in anxiodepressive-like behaviors in mice with neuropathic pain, which was induced by partial sciatic nerve ligation (PSNL). At 8 weeks after surgery, there was decreased levels of mitochondrial damage-associated molecular patterns, such as cytochrome c and mitochondrial transcription factor A, and increased level of cytosolic mitochondrial DNA in the contralateral hippocampus, suggesting the development of mitochondrial dysfunction. Type I interferon (IFN) mRNA expression in the hippocampus was also increased at 8 weeks after PSNL surgery. The restoration of mitochondrial function by curcumin blocked the increased cytosolic mitochondrial DNA and type I IFN expression in PSNL mice and improved anxiodepressive-like behaviors. Blockade of type I IFN signaling by anti-IFN alpha/beta receptor 1 antibody also improved anxiodepressive-like behaviors in PSNL mice. Together, these findings suggest that neuropathic pain induces hippocampal mitochondrial dysfunction followed by neuroinflammation, which may contribute to anxiodepressive-behaviors in the neuropathic pain state. Improving mitochondrial dysfunction and inhibiting type I IFN signaling in the hippocampus might be a novel approach to reducing comorbidities associated with neuropathic pain, such as depression and anxiety.<br />Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Chronic Pain complications
Chronic Pain metabolism
Chronic Pain pathology
Chronic Pain psychology
Curcumin pharmacology
Curcumin therapeutic use
Cytosol drug effects
Cytosol metabolism
DNA, Mitochondrial metabolism
Frontal Lobe metabolism
Frontal Lobe pathology
Hippocampus drug effects
Hippocampus immunology
Hippocampus metabolism
Hippocampus pathology
Microglia drug effects
Microglia immunology
Neuroinflammatory Diseases complications
Sciatic Nerve surgery
Anxiety complications
Anxiety drug therapy
Anxiety metabolism
Depression complications
Depression drug therapy
Depression metabolism
Interferon Type I antagonists & inhibitors
Interferon Type I genetics
Interferon Type I metabolism
Mitochondria drug effects
Mitochondria metabolism
Mitochondria pathology
Neuralgia complications
Neuralgia metabolism
Neuralgia pathology
Neuralgia psychology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 367
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 37327964
- Full Text :
- https://doi.org/10.1016/j.expneurol.2023.114470