Abstract
Exosomes are cellular secretory vesicles containing microRNAs (miRNAs). Once secreted, exosomes are able to attach to recipient cells and release miRNAs potentially modulating the function of the recipient cell. We hypothesized that exosomal miRNA expression in brains of patients diagnosed with schizophrenia (SZ) and bipolar disorder (BD) might differ from controls, reflecting either disease-specific or common aberrations in SZ and BD patients. The sources of the analyzed samples included McLean 66 Cohort Collection (Harvard Brain Tissue Resource Center), BrainNet Europe II (BNE, a consortium of 18 brain banks across Europe) and Boston Medical Center (BMC). Exosomal miRNAs from frozen postmortem prefrontal cortices with well-preserved RNA were isolated and submitted to profiling by Luminex FLEXMAP 3D microfluidic device. Multiple statistical analyses of microarray data suggested that certain exosomal miRNAs were differentially expressed in SZ and BD subjects in comparison to controls. RT-PCR validation confirmed that two miRNAs, miR-497 in SZ samples and miR-29c in BD samples, have significantly increased expression when compared to control samples. These results warrant future studies to evaluate the potential of exosome-derived miRNAs to serve as biomarkers of SZ and BD.
Highlights
Knowing which molecules are altered in neuropsychiatric patients would represent a crucial step towards uncovering mechanisms of the development of neuropshychiatric diseases and generating more successful therapeutic strategies
Bonferroni Step-down Holm Correction was applied to correct for multiple comparisons [39]. This correction resulted in the absence of significantly differentially expressed miRNAs in bipolar disorder (BD) samples, while the expression of only three miRNAs was significantly enhanced in SZ samples in comparison to controls and to BD (Table S1)
We examined how the expression of these 21 topranked miRNAs might influence the clustering of our samples
Summary
Knowing which molecules are altered in neuropsychiatric patients would represent a crucial step towards uncovering mechanisms of the development of neuropshychiatric diseases and generating more successful therapeutic strategies. Dysregulation of miRNAs in brains of patients diagnosed with schizophrenia (SZ) [2] and other neuropsychiatric disorders is plausible considering that many miRNAs are expressed in human brain [3] where they regulate neuronal development [4] and differentiation [5] including dendritic spine development [6] and plasticity [7],[8], as well as cognitive functions [9]. The target analysis of another reported set of differentially expressed miRNAs in the PFCs of SZ patients revealed many genes implicated in signaling pathways [11]. While a specific BD miRNA profile has not yet been established, alterations in neurochemical regulation including an excess in signaling activity have been associated with BD [12]
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