Mirtazapine treatment in a young female mouse model of Rett syndrome identifies time windows for the rescue of early phenotypes

Gutiérrez, Javier Flores; Natali, Giulia; Giorgi, Jacopo; Leonibus, Elvira De; Tongiorgi, Enrico

doi:10.1016/j.expneurol.2022.114056

Cited by 2 publications

(1 citation statement)

References 61 publications

(117 reference statements)

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“…Neurobehavioral functions were assessed through the use of the modified Garcia test, Rotarod test and Water maze at 24 h and 72 h following ICH by a blinded investigator as previously described. 26,27 In the modified Garcia test, seven distinct aspects were evaluated, including spontaneous activity, axial sensation, vibrissae touch, limb symmetry, lateral turning, forelimb walking, and climbing. Each test was scored from either 0-3 or 1-3, yielding a maximum deficit score of 21, with a higher score indicating superior neurological function.…”

Section: Neurobehavioral Function Testmentioning

confidence: 99%

Integrating network pharmacology and transcriptomic omics reveals that akebia saponin D attenuates neutrophil extracellular traps‐induced neuroinflammation via NTSR1/PKAc/PAD4 pathway after intracerebral hemorrhage

Gu,

Ye,

Chen

et al. 2023

The FASEB Journal

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Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti‐inflammatory activities and blood–brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post‐ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti‐NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti‐NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post‐ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti‐NETs properties.

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Section: Neurobehavioral Function Testmentioning

confidence: 99%