1. Curcumin–cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress
- Author
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Martial Caillaud, Laurence Richard, Zeina Msheik, Jean-Michel Vallat, Vincent Sol, Robert Granet, Alexis Desmoulière, Laetitia Vignaud, Franck Sturtz, Gautier M.A. Ndong-Ntoutoume, Pierre-Antoine Faye, Frédéric Favreau, Fabrice Billet, Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Virginia Commonwealth University (VCU), PEIRENE (PEIRENE), Service de Neurologie [CHU Limoges], CHU Limoges, Centre de référence national neuropathies périphériques rares [CHU Limoges], and Service de Biochimie et Génétique Moléculaire [CHU Limoges]
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Curcumin ,Peripheral neuropathy ,[SDV]Life Sciences [q-bio] ,Motor nerve ,Encoplasmic reticulum ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Myelin ,Myelination ,0302 clinical medicine ,In vivo ,Charcot-Marie-Tooth Disease ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Cellulose ,Cyclodextrins ,biology ,Chemistry ,Myelin protein zero ,Curcumin-cyclodextrin/cellulose nanocrystal ,3. Good health ,Myelin basic protein ,Rats ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Phenotype ,Charcot-Marie-Tooth-1A ,PMP22 ,Oxidative stress ,biology.protein ,Nanoparticles ,Sciatic nerve ,Rats, Transgenic ,030217 neurology & neurosurgery - Abstract
International audience; The most prevalent form of Charcot-Marie-Tooth disease (CMT type 1A) is characterized by duplication of the PMP22 gene, peripheral dysmyelination and decreased nerve conduction velocities leading to muscle weakness. Recently, oxidative stress was reported as a feature in CMT1A patients. Curcumin exhibits antioxidant activities and has shown beneficial properties on peripheral nerves. However, curcumin presents unfavorable pharmacokinetics. We developed curcumin-cyclodextrin/cellulose nanocrystals (Nano-Cur) to bypass this limitation. The present study investigated the therapeutic potential of Nano-Cur in vitro in Schwann cells (SCs) and in vivo in the transgenic CMT1A rat model. In vitro, Nano-Cur treatment (0.01 μM for 8 h) reduced reactive oxygen species and improved mitochondrial membrane potential in CMT1A SCs. Moreover, Nano-Cur treatment (0.01 μM for 1 week) increased the expression of myelin basic protein in SC/neuron co-cultures. Preliminary in vivo experiments carried out in WT rats showed that intraperitoneal (i.p.) injection of Nano-Cur treatment containing 0.2 mg/kg of curcumin strongly enhanced the bioavailability of curcumin. Afterwards, in 1-month-old male CMT1A rats, Nano-Cur treatment (0.2 mg/kg/day, i.p. for 8 weeks) significantly improved sensori-motor functions (grip strength, balance performance, and mechanical and thermal sensitivities). Importantly, sensory and motor nerve conduction velocities were improved. Further histological and biochemical analyses indicated that myelin sheath thickness and myelin protein expression (myelin protein zero and PMP22) were increased. In addition, oxidative stress markers were decreased in the sciatic nerve and gastrocnemius muscle. Finally, Nrf2 expression and some major antioxidant enzymes were increased in sciatic nerve. Therefore, Nano-Cur significantly improved cellular, electrophysiological, and functional features of CMT1A rats.
- Published
- 2020
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