Skin-brain axis signaling mediates behavioral changes after skin wounding

Area of Science:

• Neuroscience
• Immunology
• Wound Healing

Background:

• Chronic wounds are frequently linked to cognitive dysfunction and depression.
• The underlying mechanisms connecting skin wounds to these neurological and psychological changes remain unclear.

Purpose of the Study:

• To investigate the causal relationship between peripheral skin wounding and subsequent behavioral and cognitive alterations.
• To explore the potential skin-to-brain signaling pathways involved.

Main Methods:

• Excisional skin wounds were created in female C57BL/6 mice, and their behavior and cognitive functions were compared to unwounded controls.
• Hippocampal gene expression (Tnfa, Nod2, GR/Nr3c1, Nr3c2) and prefrontal cortex neurotransmitter turnover were analyzed.
• Serum levels of cytokines (IL6, TNFα, TGFβ), catecholamines, and corticosterone were measured.

Main Results:

• Wounded mice exhibited anxiety-like behaviors, impaired recognition memory, and coping deficits six days post-wounding.
• Increased hippocampal expression of Tnfa, Nod2, and glucocorticoid receptors was observed in wounded animals.
• Elevated serum IL6 levels were detected in wounded mice, while other systemic mediators like corticosterone and TNFα did not differ significantly.

Conclusions:

• Peripheral skin wounding can induce significant behavioral and cognitive deficits, suggesting a skin-to-brain communication pathway.
• This signaling may be mediated by elevated serum IL6 or direct neuronal pathways, independent of systemic stress hormones.
• Altered hippocampal expression of inflammatory mediators and pattern recognition receptors (PRRs) following wounding may underlie the observed behavioral impairments.