Role of NOX-2 derived oxidative stress, endothelial function and gut-derived lipopolysaccharides in children affected by paediatric acute-onset neuropsychiatric syndrome (PANS).

Anno
2021
Proponente Lorenzo Loffredo - Professore Associato
Sottosettore ERC del proponente del progetto
LS4_7
Componenti gruppo di ricerca
Componente Categoria
Anna Maria Zicari Componenti strutturati del gruppo di ricerca
Giulia Brindisi Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca
Alberto Spalice Componenti strutturati del gruppo di ricerca
Componente Qualifica Struttura Categoria
Nazareno Paolocci Professor Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Victoria Ivanov Professor State University of Medicine and Pharmacy "Nicolae Testemitanu"- Moldavian Research Institute of Cardiology, Chisinau, Republic of Moldova. Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Marco Casciaro Doctor Azienda Universitaria Policlinico Umberto I, Dipartimento di SCIENZE CLINICHE INTERNISTICHE, ANESTESIOLOGICHE E CARDIOVASCOLARI Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Roberta Marti Professor Azienda Universitaria Policlinico Umberto I, Dipartimento di SCIENZE CLINICHE INTERNISTICHE, ANESTESIOLOGICHE E CARDIOVASCOLARI Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Abstract

Paediatric acute-onset neuropsychiatric syndrome (PANS) is a wide spectrum of disorders characterised by sudden onset of obsessive-compulsive disorder (OCD).
A particular subtype of PANS is considered the paediatric autoimmune neuropsychiatic disorders associated with streptococcal infections syndrome (PANDAS) that identifies patients with acute onset of OCD and/or tic disorders related to Group-A streptococcus infection.
This disease is characterized by a neuroinflammatory process that could be generated by increased oxidative stress. Animal studies in PANS/PANDAS models have hypothesized a damage to the vascular system underlying the neuroinflammation.
NADPH oxidase is one of the most important source of O2- in human. Oxidative stress generated by NADPH oxidase modulates endothelial function. Considering that
previous studies have shown gut dysbiosis in PANS/PANDAS subjects, the LPS generated by the gut microbiota could translocate into the circulation activating NADPH oxidase-2 and TLR-4 and generating endothelial dysfunction and vascular damage to the brain barrier.
No studies have been explored this issue. Thus, the objective of this study is to evaluate NADPH oxidase-2 (NOX2) activation by serum sNOX2-dp levels, as well as 8-iso-prostaglandin F2-alpha (8-iso-PGF2-alpha) and lipopolysaccharide (LPS) of PANS and PANDAS patients. Serum zonulin will be used as intestinal permeability assay. Furthermore, artery endotheliial dysfunction will be evaluated with flow-mediated dilation technique.
Ninety consecutive subjects, including 30 children affected by PANDAS and 30 with PANS and 30 controls matched for age and gender will be recruited.
The results of this research could increase the knowledge in this field evaluating the role of dysbiosis, NOX2 generated oxidative stress and endothelial dysfunction in patients with PANS and PANDAS that could be useful to plann future studies with probiotics or antioxidants to reduce the neurologic crisis of these patients.

ERC
LS4_7, LS5_8, LS5_5
Keywords:
MICROBIOTA GASTROINTESTINALE, PEDIATRIA, NEUROPSICOLOGIA, IDENTIFICAZIONE DEL DANNO, MEDICINA INTERNA

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