Association between miRNAs expression and cognitive performances of Pediatric Multiple Sclerosis patients: A pilot study

Abstract

Introduction The Pediatric onset of Multiple Sclerosis (PedMS) occurs in up to 10% of all cases. Cognitive impairment is one of the frequent symptoms, exerting severe impact in patients’ quality of life and school performances. The underlying pathogenic mechanisms are not fully understood, and molecular markers predictive of cognitive dysfunctions need to be identified. On these grounds, we searched for molecular signature/s (i.e., miRNAs and target genes) associated with cognitive impairment in a selected population of PedMS patients. Additionally, changes of their regional brain volumes associated with the miRNAs of interest were investigated. Methods Nineteen PedMS subjects received a full cognitive evaluation; total RNA from peripheral blood samples was processed by next‐generation sequencing followed by a bioinformatics/biostatistics analysis. Results The expression of 11 miRNAs significantly correlated with the scores obtained at different cognitive tests; among the others, eight miRNAs correlated with the Trail Making Tests. The computational target prediction identified 337 genes targeted by the miRNAs of interest; a tangled network of molecular connections was hypothesized, where genes like BST1, NTNG2, SPTB, and STAB1 , already associated with cognitive dysfunctions, were nodes of the net. Furthermore, the expression of some miRNAs significantly correlated with cerebral volumes, for example, four miRNAs with the cerebellum cortex. Conclusions As far as we know, this is the first evaluation exploring miRNAs in the cognitive performances of PedMS. Although none of these results survived the multiple tests’ corrections, we believe that they may represent a step forward the identification of biomarkers useful for monitoring and targeting the onset/progression of cognitive impairments in MS.

Williams Syndrome, Human Self-Domestication, and Language Evolution

“…This gene is also a candidate for Schinzel-Giedion syndrome, a condition entailing severe developmental delay and occasional epilepsy ( Ko et al, 2013 ; Miyake et al, 2015 ). Likewise, STAB1 , which encodes a scavenger receptor for acetylated low density lipoproteins, with an important role in defending against bacterial infections, has been found to be associated with conditions impacting on our distinctive cognitive abilities, including bipolar disorder ( Witt et al, 2014 ), Alzheimer’s disease ( Giil et al, 2017 ), and pediatric Multiple Sclerosis patients ( Liguori et al, 2019 ). CASP7 encodes a caspase that contributes to the cleavage of nuclear substrates during neuronal apoptosis ( Hayashi et al, 2006 ).…”

Cognitive Functioning in Patients with Pediatric-Onset Multiple Sclerosis, an Updated Review and Future Focus

“…Research has consistently found that approximately one third of pediatric patients with MS suffer from neurocognitive impairment. This is somewhat less than what is typically reported in the adult literature, which ranges from 50% [21,22,23,24] to close to 70% [25,26]. Early diagnosis of cognitive dysfunction can be extremely important in POMS, given that physical status can be well preserved.…”

“…Genetic risk factors and interactions between several risk factors (second-hand smoke, genetic predisposition, physical functioning) were also evaluated [119,120,121]. A recent pilot study [26] searched for genetic signatures associated with cognitive impairment in patients with POMS. They found that expressions of 11 miRNAs associated with cognitive test performance.…”

Molecular Biomarkers in Multiple Sclerosis and Its Related Disorders: A Critical Review

“…It is reported that protective miR-199a, pathogenic miR-320, miR-155, miR-142-3p and miR-142 are increased in MS lesions or peripheral blood mononuclear cells (PBMCs) [ 9 , 10 , 11 ]. On the other hand, miR-219, miR-34a, miR-103, miR-182-5p, miR-124 and miR-15a/b are decreased in the Cerebrospinal fluid (CSF), Tregs or PBMCs of MS patients [ 9 , 10 , 12 , 13 , 14 ]. There is a strong correlation between miRNAs and various manifestations of MS such as cognitive dysfunction and oxidative status, which can result in depression or fatigue [ 9 , 10 , 11 , 12 , 13 , 14 ].…”