Chronic CXCL10 alters neuronal properties in rat hippocampal culture, 2009, Cho et al

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jnmaciuch

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Chronic CXCL10 alters neuronal properties in rat hippocampal culture

Cho, Jungsook; Nelson, Thomas E.; Bajova, Hilda; Gruol, Donna L.

Abstract
The chemokine CXCL10 is expressed in the central nervous system (CNS) during neuroinflammatory conditions. Neurons express CXCR3, the receptor for CXCL10, and neuronal function has been shown to be altered by acute exposure to CXCL10. Little is known about the effects of chronic exposure to CXCL10 on neuronal function. Results from our studies show that chronic exposure of cultured rat hippocampal neurons to CXCL10 results in altered levels of protein for GABA and glutamate receptors and altered synaptic network activity. These effects of CXCL10 may contribute to altered CNS function that occurs in some chronic neuroinflammatory conditions.

Web | Journal of Neuroimmunology
https://doi.org/10.1016/j.jneuroim.2008.12.007 (Paywalled)
 
CXCL10 activation of CXCR3 receptors in neurons was found to be a driver of sickness behavior in animal models from this paper:
Hutan

Thread 'Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment, 2016, Blank +'

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Thomas Blank 1 ∙ Claudia N. Detje 2 ∙ Alena Spieß 1 ∙ Nora Hagemeyer 1 ∙ Stefanie M. Brendecke 1 ∙ Jakob Wolfart 3 ∙ Ori Staszewski 1 ∙ Tanja Zöller 1 ∙ Ismini Papageorgiou 4 ∙ Justus Schneider 4 ∙ Ricardo Paricio-Montesinos 1 ∙ Ulrich L.M. Eisel 5∙ Denise Manahan-Vaughan 6 ∙ Stephan Jansen 6 ∙ Stefan Lienenklaus 2, 7 ∙ Bao Lu 8 ∙ Yumiko Imai 9 ∙ Marcus Müller 10 ∙ Susan E. Goelz 11 ∙ Darren P. Baker 12 ∙ Markus...
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I thought this paper was interesting because if CXCL10 is relevant in ME/CFS, the findings from this paper could help explain some aspects of the illness that members have reported, specifically sensory sensitivity and finding relief from medications like Xanax that modulate neuron excitability.

In this thread I was also discussing the possibility of calcium flux in neurons causing mtDNA release under the right conditions, which would generate an interferon response in neurons:

Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice, Li et al. (2024)

Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice Wenwen Li, Jiarui Li, Jing Li, Chen Wei, Tal Laviv, Meiyi Dong, Jingran Lin, Mariah Calubag, Lesley A Colgan, Kai Jin, Bing Zhou,, Ying Shen, Haohong Li, Yihui Cui, Zhihua Gao, Tao Li, Hailan Hu...
s4me.info s4me.info

This paper might provide an explanation for how that feedback loop could get locked in. With certain genetic predispositions, the feedback mechanism would be: Prolonged CXCL10 signaling from infection -> increased neuron excitability and therefore calcium flux -> increased mtDNA release through mitochondrial calcium channel VDAC -> mtDNA detecting by cGAS-STING triggers type I interferon -> type I interferon binds to IFNAR on brain epithelial cells, generating more CXCL10 -> [edit: prolonged CXCL10 signaling without infection, just driven by neuron firing].

Will come back to do more of a deep dive into the paper when I have a free moment. From my first read, the biggest limitation is that the findings come from cultured neurons, so may be missing an important physiological feedback mechanism that normally counteracts this effect in-vivo.
 
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