Dataset Information

Skin-brain axis signaling mediates behavioral changes after skin wounding.

ABSTRACT: Patients with chronic wounds often have associated cognitive dysfunction and depression with an as yet unknown mechanism for this association. To address the possible causality of skin wounding inducing these changes, behavior and cognitive functions of female C57BL/6 mice with an excisional skin wound were compared to unwounded animals. At six days post wounding, animals exhibited anxiety-like behaviors, impaired recognition memory, and impaired coping behavior. Wounded animals also had concomitant increased hippocampal expression of Tnfa, the pattern recognition receptor (PRR) Nod2, the glucocorticoid receptors GR/Nr3c1 and Nr3c2. Prefrontal cortex serotonin and dopamine turnover were increased on day six post-wounding. In contrast to the central nervous system (CNS) findings, day six post -wounding serum catecholamines did not differ between wounded and unwounded animals, nor did levels of the stress hormone corticosterone, TNFα, or TGFβ. Serum IL6 levels were, however elevated in the wounded animals. These findings provide evidence of skin-to-brain signaling, mediated either by elevated serum IL6 or a direct neuronal signaling from the periphery to the CNS, independent of systemic mediators. Wounding in the periphery is associated with an altered expression of inflammatory mediators and PRR genes in the hippocampus, which may be responsible for the observed behavioral deficits.

SUBMITTER: Fregoso DR

PROVIDER: S-EPMC8474598 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Skin-brain axis signaling mediates behavioral changes after skin wounding.

Fregoso Daniel R DR Hadian Yasmin Y Gallegos Anthony C AC Degovics Doniz D Maaga John J Keogh Ciara E CE Kletenik Isaiah I Gareau Melanie G MG Isseroff R Rivkah RR

Brain, behavior, & immunity - health 20210528

Patients with chronic wounds often have associated cognitive dysfunction and depression with an as yet unknown mechanism for this association. To address the possible causality of skin wounding inducing these changes, behavior and cognitive functions of female C57BL/6 mice with an excisional skin wound were compared to unwounded animals. At six days post wounding, animals exhibited anxiety-like behaviors, impaired recognition memory, and impaired coping behavior. Wounded animals also had concomi ...[more]

PMID: 34589779

Similar Datasets

Project description:BackgroundAdvanced triple-negative breast cancer (TNBC) is prone to brain metastasis (BrM). The precise molecular mechanism responsible for this phenomenon has not yet been completely established, so it is vital to comprehend the molecular mechanism behind it.MethodsThe protein chip analysis was conducted to identify any abnormal UBE2T protein expression in TNBC, especially BrM. Here, we used public databases and bioinformatics analysis as well as clinical samples from different cohorts to investigate the interrelationship between UBE2T/CDC42/CD276. This predicted relationship was then repeatedly validated using different in vivo and in vitro experimental methods. Additionally, multiple experimental approaches were implemented, encompassing western blotting, Co-IP, GST pull-down, flow cytometry, mass spectrometry, immunofluorescence, immunohistochemistry, and qRT-PCR to reveal the molecular mechanism of UBE2T-mediated immune escape and BrM.ResultsOur results indicate that expressed at elevated levels in breast cancer, UBE2T is negatively linked to patient prognosis, especially in BrM of TNBC. Data from clinical samples from our different cohorts and TCGA indicate a significant correlation between UBE2T and immunosuppression. Mechanistically, UBE2T directly interacts with CDC42, promoting its K48-linked polyubiquitination and proteasomal degradation, thereby inhibiting CDC42 from degrading CD276 via the autophagy-lysosomal pathway, indirectly upregulating CD276 and thereby impairing the CD8+ T cells function, ultimately mediating tumor immune escape and BrM. Finally, animal experimental results also showed that inhibition of UBE2T elevated the TNBC sensitivity to immune checkpoint CD276 blockade and inhibited BrM of TNBC.ConclusionsIn conclusion, our results indicate a new mechanism whereby UBE2T-mediated ubiquitination positively controls the UBE2T/CDC42/CD276 axis to upregulate tumor cell expression of CD276 and thereby impair CD8+ T cells function, ultimately leading to tumor cell immune escape and BrM.

Dataset Information

Skin-brain axis signaling mediates behavioral changes after skin wounding.

Publications

Skin-brain axis signaling mediates behavioral changes after skin wounding.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets