Neuroinflammation driven by TLR7 activation in mice results in a global inflammatory response driving circuit-specific changes in neuronal gene expression DOI Creative Commons
Kirstyn Gardner-Stephen,

Robin J Carvajal-Quisilema,

Lilya Andrianova

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Interactions between the brain and immune system play a key role in aetiology of disorders, with inflammation emerging as potential causal factor subsets major depressive disorder, particularly those resistant to treatment. The mechanisms through which activation can drive symptoms remain elusive, limiting ability develop new targeted therapies. Using mouse model neuroinflammation, involving TLR7/8 agonist, we found central systemic alongside anhedonia-like behaviours, altered thalamostriatal signalling infiltration peripheral cells into brain. Here, sought use combined whole-brain transcriptome spatial transcriptomics approaches determine whether Aldara-driven neuroinflammation resulted consistent neurobiological changes throughout We evidence strong brain, astrocytes displaying inflammatory profile that was relatively uniform throughout. However, this global signal led regionally-specific gene expression, reduced expression genes associated synaptic function areas underlying mood anxiety, such ventral striatum amygdala. Our data suggest regulate neuronal response inflammation.

Language: Английский

Neuroinflammation driven by TLR7 activation in mice results in a global inflammatory response driving circuit-specific changes in neuronal gene expression DOI Creative Commons
Kirstyn Gardner-Stephen,

Robin J Carvajal-Quisilema,

Lilya Andrianova

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Interactions between the brain and immune system play a key role in aetiology of disorders, with inflammation emerging as potential causal factor subsets major depressive disorder, particularly those resistant to treatment. The mechanisms through which activation can drive symptoms remain elusive, limiting ability develop new targeted therapies. Using mouse model neuroinflammation, involving TLR7/8 agonist, we found central systemic alongside anhedonia-like behaviours, altered thalamostriatal signalling infiltration peripheral cells into brain. Here, sought use combined whole-brain transcriptome spatial transcriptomics approaches determine whether Aldara-driven neuroinflammation resulted consistent neurobiological changes throughout We evidence strong brain, astrocytes displaying inflammatory profile that was relatively uniform throughout. However, this global signal led regionally-specific gene expression, reduced expression genes associated synaptic function areas underlying mood anxiety, such ventral striatum amygdala. Our data suggest regulate neuronal response inflammation.

Language: Английский

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