Moringin activates Wnt canonical pathway by inhibiting GSK3β in a mouse model of experimental autoimmune encephalomyelitis

Sabrina Giacoppo,1 Thangavelu Soundara Rajan,1 Gina Rosalinda De Nicola,2 Renato Iori,2 Placido Bramanti,1 Emanuela Mazzon1 1IRCCS Centre Neurolesi “Bonino-Pulejo”, Messina, Italy; 2Council for Agricultural Research and Economics, Research Centre for Industrial Crops (CREA-CIN), Bologna, Italy Abstract: Aberrant canonical Wnt–β-catenin signaling has been reported in multiple sclerosis (MS), although the results are controversial. The present study aimed to examine the role of the Wnt–β-catenin pathway in experimental MS and also to test moringin (4-[α-L-rhamnopyranosyloxy]-benzyl isothiocyanate), resulting from exogenous myrosinase hydrolysis of the natural phytochemical glucomoringin 4(α-L-rhamnosyloxy)-benzyl glucosinolate as a modulator of neuroinflammation via the β-catenin–PPARγ axis. Experimental autoimmune encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with MOG35–55. Released moringin (10 mg/kg glucomoringin +5 µL myrosinase/mouse) was administered daily for 1 week before EAE induction and continued until mice were killed on day 28 after EAE induction. Our results clearly showed that the Wnt–β-catenin pathway was downregulated in the EAE model, whereas moringin pretreatment was able to avert this. Moringin pretreatment normalizes the aberrant Wnt–β-catenin pathway, resulting in GSK3β inhibition and β-catenin upregulation, which regulates T-cell activation (CD4 and FoxP3), suppresses the main inflammatory mediators (IL-1β, IL-6, and COX2), through activation of PPARγ. In addition, moringin attenuates apoptosis by reducing the expression of the Fas ligand and cleaved caspase 9, and in parallel increases antioxidant Nrf2 expression in EAE mice. Taken together, our results provide an interesting discovery in identifying moringin as a modulator of the Wnt–β-catenin signaling cascade and as a new potential therapeutic target for MS treatment. Keywords: Wnt–β-catenin pathway, GSK3β, multiple sclerosis, moringin, PPARγ, apoptosis&nbsp

Non-invasive brain stimulation in human stroke survivors

The use of electromagnetic currents toward understanding and curing human disease has long been of interest. In the 1980s, a dramatic increase in our understanding of brain function, along with parallel improvements in non-invasive brain stimulation (NIBS) technologies, subsequently caused rapid expansion of the field. Intraoperative monitoring techniques that incorporated single pulse stimulation were developed concurrently for the purpose of measuring corticospinal integrity (Merton & Morton, 1980a, 1980b); however, with the introduction of transcranial magnetic stimulation (TMS), the use of NIBS decisively exploded, opening a new window into the exploration and modulation of the brain (Barker and Jalinous, Lancet, 1(8437):1106–1107, 1985). Single pulse TMS, used initially to study inter-cortical physiology of the intact corticospinal tract, was thereafter investigated toward the rehabilitation of neurological and psychiatric conditions