Citation: Kichukova TM, Popov NT, Ivanov IS, Vachev TI. Profi ling of circulating serum microRNAs in children with autism spectrum disorder using stem-loop qRT-PCR assay.Folia Medica 2017;59(1): 43-52. doi: 10.1515/folmed-2017-0009 Background: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions. Aim: The aim of this study was to test whether circulating miRNAs display diff erential expression profi le in serum of ASD patients. Patients and methods:The relative expression levels of 42 miRNAs were analyzed by stem-loop qRT-PCR assay in the serum of ASD patients compared to healthy controls. Results: The results indicated that 11 miRNAs in ASD patients were substantially higher expressed than these in control subjects, and 29 miRNAs were lower expressed, respectively. In addition, target gene analysis displayed that the altered serum miRNAs targeted some important genes like alpha 1C subunit of voltagedependent calcium channel, L type, (CACNA1C), beta 1 subunit of voltage-dependent calcium channel (CACNB1) and other genes involved in epigenetic processes like dicer 1, coding ribonuclease type III (DICER). Conclusion: Our results suggested that diff erentially expressed miRNAs in serum might be involved in ASD molecular pathways, and serum miR- 424-5p, miR-197-5p, miR-328-3p, miR-500a-5p, miR-619-5p, miR-3135a, miR-664a-3p, and miR365a-3p might be able to serve as potential biomarkers for ASD because they displayed signifi cant alterations in the expression profi le in children diagnosed with ASD.

Autism spectrum disorder is an entity that reflects a scientific consensus that several previously separated disorders are actually a single spectrum disorder with different levels of symptom severity in two core domains - deficits in social communication and interaction, and restricted repetitive behaviors. Autism spectrum disorder is diagnosed in all racial, ethnic and socioeconomic groups and because of its increased prevalence, reported worldwide through the last years, made it one of the most discussed child psychiatric disorders. In term of aetiology as several other complex diseases, Autism spectrum disorder is considered to have a strong genetic component.

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Neuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD), major depressive disorder (MDD) and autism spectrum disorder (ASD), are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post-transcriptional level, microRNAs (miRNAs) play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases.

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Viroids, small RNA pathogens capable of infecting flowering plants, coexist in the field with parasitic plants that infest many crops. The ability of viroids to be exchanged between host and parasitic plants and spread in the latter has not yet been investigated. We studied the interaction between the Potato spindle tuber viroid (PSTVd) and Branched bromrape (Orobanche ramosa) using the tomato, Solanum lycopersicon, as a common host. We report the long distance trafficking of PSTVd RNA via the phloem from tomato to O. ramosa, but not vice versa. Furthermore, we identify O. ramosa as a novel host with the ability to facilitate the replication and processing of PSTVd. Finally, molecular variants of PSTVd with single nucleotide substitutions that replicate with different efficiencies in tomato were isolated from O. ramosa.

Epidemiological evidence suggests that etiology of schizophrenia may involve both the influence of genetic factors specific for the individual and the impact of the environment. It is quite likely that a crucial role in the disease development is played by molecular mechanisms mediating the interaction between genes and environment. Modern research have shown that epigenetic mechanisms or chemical modifications of deoxyribonucleic acids (DNA) and histone proteins remain unstable throughout life and can be changed by environmental factors. Thus the epigenetic mechanisms outline an attractive molecular hypothesis of the environment modelling role and the environmental contribution to schizophrenia progression. We give in the present study a general outline of schizophrenia as a pathological entity and discuss the role and involvement of environment versus genetic determinant (nature versus nurture) in the pathophysiolgical processes. Additionally, we focus on DNA methylation discussing the evidence for the role of that process in schizophrenia. Thirdly, we review the post-translational histone modifications and their role in schizophrenia. These investigations might surely lead further to the development of epigenetic therapy that looks promising in regard to symptom alleviation and the disease-associated cognitive deficit.

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