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

Abstract:

:We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit. 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 the mdx 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 in mdx 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 in mdx 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 improve mdx neurons function, including cognitive functions.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Lopez JR,Uryash A,Kolster J,Estève E,Zhang R,Adams JA

doi

10.1007/s12035-018-1018-8

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

8680-8694

issue

11

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-1018-8

journal_volume

55

pub_type

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