Dysregulated nitric oxide signaling as a candidate mechanism of fragile X syndrome and other neuropsychiatric disorders

Advances in the understanding of the genetic causes of some neuropsychiatric disorders are having an impact on clinical practice as direct mutation analysis becomes possible. Mutation analysis is now available in UK Health Service diagnostic laboratories for Huntington's disease (HD) and the fragile X syndrome (FRAXA). Psychiatrists need to be familiar with issues surrounding presymptomatic and diagnostic testing in HD and diagnostic and carrier testing in FRAXA. They may be asked to assist clinical geneticists in the assessment of candidates for HD presymptomatic testing and a suggested mode of assessment is described here. The procedure for HD will provide the model for use with other familial neuropsychiatric disorders of late onset, notably familial Alzheimer's disease (FAD). Testing for FAD is already possible in conjunction with research laboratories in the few families where a mutation has been discovered and we shall have more tests for FAD within a few years.

Download Full-text

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/8548910 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Elena Lima-Cabello ◽

Francisco Garcia-Guirado ◽

Rocio Calvo-Medina ◽

Rajaa el Bekay ◽

Lucia Perez-Costillas ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Fragile X Syndrome ◽

Fragile X ◽

Nuclear Factor ◽

Brain Areas ◽

Nitric Oxide Metabolism ◽

Oxide Synthase ◽

Nos Isoforms

Background.Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model.Methods.This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas.Results.Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes.Conclusions.These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

Download Full-text