Increased hippocampal excitability in miR-324-null mice.

Autor: Hayman DJ; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Modebadze T; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Charlton S; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Cheung K; Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Soul J; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Lin H; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Hao Y; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.; Orthopedics Department, First Hospital of Shanxi Medical University, Yingze District, Taiyuan, 030000, China., Miles CG; Translational and Clinical Research Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Tsompani D; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Jackson RM; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Briggs MD; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Piróg KA; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Clark IM; School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK., Barter MJ; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Clowry GJ; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., LeBeau FEN; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK., Young DA; Biosciences Institute, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. david.young@ncl.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 May 17; Vol. 11 (1), pp. 10452. Date of Electronic Publication: 2021 May 17.
DOI: 10.1038/s41598-021-89874-1
Abstrakt: MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3'UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease.
Databáze: MEDLINE
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