Inhibition of MicroRNA-129-5p Promotes Neuroinflammation and Cognitive Impairment

Abstract

Frontotemporal dementia (FTD) is a neurodegenerative disorder that causes the frontal and temporal lobes of the brain to deteriorate over time. This leads to changes in behavior, language problems, and a loss of mental abilities. Dysregulation of microRNAs (miRNAs) has been linked to several neurodegenerative diseases, including FTD, which suggests that they could be used as both biomarkers and therapeutic targets. We looked at smallRNA sequencing data from the frontal and temporal brain tissue of FTD patients with mutations in the MAPT, GRN, or C9orf72 genes, as well as brain tissue from people without dementia. The objective of this study was to find out what role miR-129-5p plays in FTD. We discovered that miR-129-5p was abundant in neurons, and knocking it out in a neuron-glia mixed culture increased neuroinflammation and was linked to astrocyte activation. When astrocytes without miR-129-5p were cultured with primary neurons, it had a negative effect on synaptic plasticity. Inhibiting miR-129-5p in mice resulted in hippocampus-dependent learning memory impairment and cognitive dysfunction. This study emphasizes the role of miR-129-5p in regulating neuronal activity and its potential as a therapeutic target for FTD. The results show that miR-129-5p plays a crucial role in controlling neuroinflammation and synaptic plasticity in FTD. The research sheds light on the molecular mechanisms underlying FTD and reveals potential therapeutic targets for this devastating disease.