Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK/NF-κB signaling pathway

Guo, Peipei; Liu, Lan; Yang, Xin; Li, Mengting; Zhao, Qiu; Wu, Huisheng

doi:10.1016/j.cellsig.2022.110300

Cited by 11 publications

(7 citation statements)

References 42 publications

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“…It has been demonstrated that irisin was closely related to the ERK1/2 pathway 29 – 31 . Our data showed that irisin (10 or 20 nM) treatment activated the ERK1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway

Hu,

Chen,

Chen

et al. 2023

Sci Rep

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Esketamine provides an immediate and noticeable antidepressant effect, although the underlying molecular processes are yet unclear. Irisin induced by aerobic exercise has been implicated in the alleviation of depressive symptoms, whether irisin expression responds to the administration of esketamine remains unknown. In this study, we found that irisin was reduced in the hippocampus and peripheral blood of chronic unpredictable mild stress (CUMS) mice, whereas the irisin level was rescued by esketamine treatment. The reduction of PGC-1α expression (transcriptional regulator of irisin gene expression) in the CUMS mice was rescued by esketamine treatment, PGC-1α knockdown significantly reduced the irisin level induced by esketamine. Additionally, FNDC5/irisin-knockout mice developed more severe depressant-like behaviors than wild-type mice under CUMS stimulation, with an attenuated the antidepressant effect of esketamine. Further research indicated that irisin-mediated modulation of esketamine on depressive-like behaviors in CUMS mice involved the ERK1/2 pathway. Overall, the PGC-1α/irisin/ERK1/2 signaling activation may be a new mechanism underlying the antidepressant activity of esketamine, denoting that irisin may be a promising therapeutic target for the treatment of depression.

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“…It has been demonstrated that irisin was closely related to the ERK1/2 pathway 29 – 31 . Our data showed that irisin (10 or 20 nM) treatment activated the ERK1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway

Hu,

Chen,

Chen

et al. 2023

Sci Rep

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“…Male Sprague-Dawley rats were divided into the following four groups using the random weight method: i) Sham, ii) normal saline (NS), iii) 3.5% NaT, and iv) 5% NaT. Sham group rats underwent Sham operation and were treated similarly without infusion (n=16), NS group rats were infused with NS solution and underwent Sham operation (n=16), whereas SAP was induced in 3.5% NaT group rats (n=80) (3, 6, 12, 24, 48 and 72 h) and 5% NaT group rats (n=80) (3, 6, 12, 24, 48 and 72 h) according to a previously reported method ( 13 , 15 , 16 ). Rats were fasted for 12 h before the operation.…”

Section: Methodsmentioning

confidence: 99%

Systemic injury caused by taurocholate‑induced severe acute pancreatitis in rats

et al. 2022

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Systemic injury plays a central role in severe acute pancreatitis (SAP). Retrograde biliopancreatic duct infusion of sodium taurocholate (NaT) is commonly used to establish SAP animal models. To better characterize the systemic injury in this model, SAP was induced in Sprague-Dawley rats by NaT administration (3.5 or 5%), followed by sacrifice at 3, 6, 9, 12, 24, 48 and 72 h. Normal saline was used as a control in Sham-operated rats. The mortality rate, ascites volume, and serum and ascitic fluid amylase and lipase activities were assessed. Multiple organ dysfunction, including dysfunction of the pancreas, lung, ileum, liver, and kidney, was investigated using hematoxylin and eosin staining. The interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in the ascitic fluid, serum, and ileum tissues were evaluated using an enzyme-linked immunosorbent assay (ELISA). Tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in ileum tissues were studied using immunofluorescence. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE) and urea levels were measured using an automatic biochemical analyzer. The results of the present study indicated that both 3.5 and 5% NaT could induce a stable elevation of pancreatitis indices, with histopathological injury of the pancreas, lungs and ileum (5% NaT). The ascitic fluid levels of IL-6 and IL-1β were increased in the 5% NaT group. ALT and AST levels increased temporarily and recovered in 72 h, without a significant increase in CRE and urea levels or apparent hepatic and renal pathological injury. In conclusion, rats with NaT-induced SAP have characteristics of necrotizing hemorrhagic pancreatitis with multiple organ injuries, including inflammatory lung injury, ischemic intestinal injury and slight liver and kidney injuries.

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“…Irisin, for example, crosses the BBB, and enriches in the brain after peripheral delivery. In various animal models, it reduces BBB leaks through inhibition of matrix metalloproteinases, peripheral immune cell infiltration and microglial activation [ 142 , 143 , 144 ]. However, in contrast to the growing experimental and clinical evidence that exercise has beneficial effects on synaptic plasticity, and neuronal and cognitive function in aging and neurodegenerative disorders, such as (preclinical) AD or Parkinson’s disease (PD), investigating its impact on microvascular integrity and motor function remains so far an understudied field [ 142 , 145 , 146 , 147 ].…”

Section: Targeting Brain Vascular Health To Preserve Microvascular In...mentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

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Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK/NF-κB signaling pathway

Cited by 11 publications

References 42 publications

Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway

Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway

Systemic injury caused by taurocholate‑induced severe acute pancreatitis in rats

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

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