In Vivo MicroRNA Detection and Quantitation in Cerebrospinal Fluid

Abstract

Objectives Alterations in miRNA expression in post-mortem brain tissue or peripheral blood have been linked to schizophrenia. Cerebrospinal fluid might provide an in vivo biomarker more directly reflecting functional changes in the brain. The goals of this study were to determine the feasibility of detecting miRNAs in cerebrospinal fluid and to compare miRNA levels in cerebrospinal fluid versus blood. Methods Four healthy volunteers and four patients with psychotic disorders underwent lumbar puncture and a blood draw. Expression of 378 validated microRNAs was assessed from each biofluid type for each subject using microarray technology. Five miRNAs were chosen for validation with qPCR. Results A substantial number of microRNAs (n=95) were exclusively or predominately detected in CSF. Levels of 35 miRNAs detected in both CSF and blood samples in all subjects were poorly correlated. Conclusions The investigation of microRNAs in CSF can help advance the understanding of psychiatric diseases and particularly schizophrenia.

The detection of microRNA associated with Alzheimer's disease in biological fluids using next-generation sequencing technologies

“…CSF represents a more suitable and relevant source of material for diagnosis of central nervous system (CNS) disorders. CSF is obtained by lumbar puncture and has been shown to contain circulating miRNAs that have been utilized in several studies for miRNA profiling of neurological and neurodegenerative disorders; including AD (Cogswell et al, 2008; Alexandrov et al, 2012; Lehmann et al, 2012), schizophrenia (Gallego et al, 2012), Multiple Sclerosis (Haghikia et al, 2012), HIV-encephalitis (Pacifici et al, 2013), traumatic brain injury (Balakathiresan et al, 2012; Patz et al, 2013) and various cancers of the CNS (Baraniskin et al, 2012a,b; Teplyuk et al, 2012). …”

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

“…Another recent study provided miRNAs quantification in schizophrenia patients serum by means of qRT-PCR and semi-nested qRT-PCR with the result of abnormal levels of nine miRNAs (miR-181b, miR-219-2-3p, miR-346, miR-195, miR-1308, miR-92a, miR-17, miR-103, and let-7g) [90]. Finally, an early investigation on miRNA expression in schizophrenia patient cerebrospinal fluid (CSF) revealed a substantial number of microRNAs (n=95) exclusively or predominately detected in CSF, although levels of 35 miRNAs detected in both CSF and blood samples in all subjects were poorly correlated [91]. To note, some discrepancies exist in the reports of various miRNA expression levels among the different postmortem studies and between these studies and the ones carried out in peripheral tissues of schizophrenia subjects.…”

Detection of Circulating miRNA Levels in Schizophrenia

“…It has been suggested that 70% of known miRNAs are expressed in the CNS, some of which are brain specific or brain-region specific (7), implying that these miRNAs may play a vital role in the development of diseases in the CNS (8). Altered miRNA levels have been found in CSF and postmortem brain of schizophrenia patients (9,10), but no ideal miRNAs have been identified in the circulation that might be used as biomarkers for clinical applications. As plasma and serum samples can be easily collected, it is important to detect circulating miRNAs of interest as diagnostic biomarkers, as opposed to potential biomarkers in other tissues.…”