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Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.
Epilepsia. 2014 Dec; 55(12):2017-27.E

Abstract

OBJECTIVE

Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS.

METHODS

miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs. In situ hybridization was used to show the spatial distribution of miRNAs in the human hippocampus. The potential effect of miRNAs on targets genes was investigated using the dual luciferase reporter gene assay.

RESULTS

miRNA expression profiling showed that 25 miRNAs were up-regulated and 5 were down-regulated in hippocampus biopsies of MTLE/HS patients compared to controls. We showed that miR-204 and miR-218 were significantly down-regulated in MTLE and HS, and both were expressed in neurons in all subfields of normal hippocampus. Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target of miR-204.

SIGNIFICANCE

miR-204 and miR-218 are developmentally regulated in the hippocampus and may contribute to the molecular mechanisms underlying the pathogenesis of MTLE and HS.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Kaalund SS
Department of Cellular and Molecular Medicine, Wilhelm Johannsen Center for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark; Research Laboratory for Stereology and Neuroscience, Bispebjerg Hospital, Copenhagen, Denmark.
Venø MT
No affiliation info available
Bak M
No affiliation info available
Møller RS
No affiliation info available
Laursen H
No affiliation info available
Madsen F
No affiliation info available
Broholm H
No affiliation info available
Quistorff B
No affiliation info available
Uldall P
No affiliation info available
Tommerup N
No affiliation info available
Kauppinen S
No affiliation info available
Sabers A
No affiliation info available
Fluiter K
No affiliation info available
Møller LB
No affiliation info available
Nossent AY
No affiliation info available
Silahtaroglu A
No affiliation info available
Kjems J
No affiliation info available
Aronica E
No affiliation info available
Tümer Z
No affiliation info available

MeSH

AdolescentAdultAnimalsCohort StudiesDenmarkEmbryo, MammalianEpilepsy, Temporal LobeExcitatory Amino Acid Transporter 2FemaleGene Expression ProfilingGene Expression RegulationGlutamate Plasma Membrane Transport ProteinsHippocampusHumansMaleMicroRNAsMiddle AgedNerve Tissue ProteinsNetherlandsPyramidal CellsReceptors, Metabotropic GlutamateReproducibility of ResultsSclerosisSequence Analysis, RNASwineYoung Adult

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25410734

Citation

Kaalund, Sanne S., et al. "Aberrant Expression of miR-218 and miR-204 in Human Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis-convergence On Axonal Guidance." Epilepsia, vol. 55, no. 12, 2014, pp. 2017-27.
Kaalund SS, Venø MT, Bak M, et al. Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance. Epilepsia. 2014;55(12):2017-27.
Kaalund, S. S., Venø, M. T., Bak, M., Møller, R. S., Laursen, H., Madsen, F., Broholm, H., Quistorff, B., Uldall, P., Tommerup, N., Kauppinen, S., Sabers, A., Fluiter, K., Møller, L. B., Nossent, A. Y., Silahtaroglu, A., Kjems, J., Aronica, E., & Tümer, Z. (2014). Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance. Epilepsia, 55(12), 2017-27. https://doi.org/10.1111/epi.12839
Kaalund SS, et al. Aberrant Expression of miR-218 and miR-204 in Human Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis-convergence On Axonal Guidance. Epilepsia. 2014;55(12):2017-27. PubMed PMID: 25410734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance. AU - Kaalund,Sanne S, AU - Venø,Morten T, AU - Bak,Mads, AU - Møller,Rikke S, AU - Laursen,Henning, AU - Madsen,Flemming, AU - Broholm,Helle, AU - Quistorff,Bjørn, AU - Uldall,Peter, AU - Tommerup,Niels, AU - Kauppinen,Sakari, AU - Sabers,Anne, AU - Fluiter,Kees, AU - Møller,Lisbeth B, AU - Nossent,Anne Y, AU - Silahtaroglu,Asli, AU - Kjems,Jørgen, AU - Aronica,Eleonora, AU - Tümer,Zeynep, Y1 - 2014/11/19/ PY - 2014/09/15/accepted PY - 2014/11/21/entrez PY - 2014/11/21/pubmed PY - 2015/3/5/medline KW - Epilepsy KW - Hippocampus KW - ROBO1 KW - miR-218 SP - 2017 EP - 27 JF - Epilepsia JO - Epilepsia VL - 55 IS - 12 N2 - OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS. METHODS: miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs. In situ hybridization was used to show the spatial distribution of miRNAs in the human hippocampus. The potential effect of miRNAs on targets genes was investigated using the dual luciferase reporter gene assay. RESULTS: miRNA expression profiling showed that 25 miRNAs were up-regulated and 5 were down-regulated in hippocampus biopsies of MTLE/HS patients compared to controls. We showed that miR-204 and miR-218 were significantly down-regulated in MTLE and HS, and both were expressed in neurons in all subfields of normal hippocampus. Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target of miR-204. SIGNIFICANCE: miR-204 and miR-218 are developmentally regulated in the hippocampus and may contribute to the molecular mechanisms underlying the pathogenesis of MTLE and HS. SN - 1528-1167 UR - https://www.unboundmedicine.com/medline/citation/25410734/Aberrant_expression_of_miR_218_and_miR_204_in_human_mesial_temporal_lobe_epilepsy_and_hippocampal_sclerosis_convergence_on_axonal_guidance_ DB - PRIME DP - Unbound Medicine ER -