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PLoS One. 2014 Aug 22;9(8):e105521. doi: 10.1371/journal.pone.0105521. eCollection 2014.

Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.

Author information

1
Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy; Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
2
Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Section of Pathology, Bellaria Hospital, Bologna, Italy.
3
Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, University of Ferrara, Ferrara, Italy.
4
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, University of Ferrara, Ferrara, Italy.
5
Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy.
6
Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; Ri.MED Foundation, Palermo, Italy.
7
Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
8
IRCCS Institute of Neurological Sciences, Section of Neurosurgery, Bellaria Hospital, Bologna, Italy.
9
IRCCS Institute of Neurological Sciences, Section of Neurology, Bellaria Hospital, Bologna, Italy.
10
IRCCS Institute of Neurological Sciences, Section of Neurology, Bellaria Hospital, Bologna, Italy; Danish Epilepsy Center, Epilepsihospital, Dianalund, Denmark.

Abstract

The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells), an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination) in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.

PMID:
25148080
PMCID:
PMC4141756
DOI:
10.1371/journal.pone.0105521
[Indexed for MEDLINE]
Free PMC Article

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