Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress.
Carlos Romá-MateoSheila Lorente-PozoLucía Márquez-ThibautMireia Moreno-EstellésConcepción GarcésDaymé GonzálezMarcos LahuertaCarmen AguadoJosé Luis García-GiménezPascual SanzFederico V PallardóPublished in: International journal of molecular sciences (2023)
Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal's life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD.
Keyphrases
- cell proliferation
- oxidative stress
- long non coding rna
- rna seq
- long noncoding rna
- resting state
- poor prognosis
- cerebral ischemia
- white matter
- single cell
- functional connectivity
- dna damage
- traumatic brain injury
- mouse model
- ischemia reperfusion injury
- multiple sclerosis
- single molecule
- transcription factor
- blood brain barrier
- high resolution
- gene expression
- diabetic rats
- lipopolysaccharide induced
- dna methylation
- cognitive impairment
- physical activity
- inflammatory response
- depressive symptoms
- risk assessment
- sleep quality
- lps induced
- smoking cessation
- bioinformatics analysis
- temporal lobe epilepsy