دورية أكاديمية

Co-Treatment With Verapamil and Curcumin Attenuates the Behavioral Alterations Observed in Williams–Beuren Syndrome Mice by Regulation of MAPK Pathway and Microglia Overexpression

التفاصيل البيبلوغرافية
العنوان: Co-Treatment With Verapamil and Curcumin Attenuates the Behavioral Alterations Observed in Williams–Beuren Syndrome Mice by Regulation of MAPK Pathway and Microglia Overexpression
المؤلفون: Ortiz-Romero, Paula, González-Simón, Alejandro, Egea, Gustavo, Pérez-Jurado, Luis A., Campuzano, Victoria
المصدر: Front Pharmacol
بيانات النشر: Frontiers Media S.A.
Frontiers Media
سنة النشر: 2021
مصطلحات موضوعية: Pharmacology, psy, envir
الوصف: Williams–Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there are currently no effective treatments. We investigated the progression of behavioral deficits present in WBS complete deletion (CD) mice, after chronic treatment with curcumin, verapamil, and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and, thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism. CD mice showed an increased density of activated microglia in the motor cortex and CA1 hippocampal region, which was prevented by co-treatment. Behavioral improvement correlated with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation to the control of synaptic transmission, and inflammation. Therefore, the results show that co-treatment prevented behavioral deficits by recovering altered gene expression in the cortex of CD mice and reducing activated microglia. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369570Test/
الإتاحة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369570Test/
حقوق: undefined
رقم الانضمام: edsbas.D9F2444B
قاعدة البيانات: BASE