Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons

In this study, we assessed the potential therapeutic properties of the whole body periodic acceleration (pGz) to ameliorate the pathology observed in cortical neurons from themdx mouse. pGz adds small pulses to the circulation, thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of nitric oxide (NO). We found [Ca2+]i and [Na+]i overload along with reactive oxygen species (ROS) overproduction inmdx neurons and cognitive dysfunction.mdx neurons showed increased activity of superoxide dismutase, glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell viability.mdx neurons were more susceptible to hypoxia-reoxygenation injury than WT. pGz ameliorated the [Ca2+]i, and [Na+]i elevation and ROS overproduction and further increased the activities of superoxide dismutase, glutathione peroxidase and reduced the malondialdehyde and calpains. pGz diminished cell damage and elevated [Ca2+]i during hypoxia-reoxygenation and improved cognitive function inmdx mice. Moreover, pGz upregulated the expression of utrophin, dystroglycan- β and CAPON, constitutive nitric oxide synthases, prosaposin, brain-derived neurotrophic, and glial cell line-derived neurotrophic factors. The present study demonstrated that pGz is an effective therapeutic approach to improvemdx neurons function, including cognitive functions.

Source: Molecular Neurobiology - October 5, 2018 Category: Neurology Source Type: research