The study of miR-34c high-fat diet and neurodegenerative diseases

Abstract

For neurodegenerative diseases despite of genetic predisposition in some individuals environmental factors affect disease risk and progression through epigenetic regulation Our thesis aims to investigate the impacts of post-transcriptional and post-translational control schemes - one via microribonucleic acid (miRNAs) and another through diet on the top two neurodegenerative diseases - Alzheimer’s and Parkinson’s disease miRNAs are increasingly recognized as key regulators in neurodegenerative diseases Our first study hypothesized that miR-34c a miRNA expressed in mammalian hippocampus could induce memory impairment akin to that of patients with Alzheimer’s disease (AD) in mice We showed that miR-34c overexpression in hippocampal neurons negatively regulated dendritic length and spine density Hippocampal neurons transfected with miR-34c had shorter dendrites on average and fewer filopodia and spines than those not transfected with miR-34c Because dendrites and synapses are key sites for signal transduction and fundamental structures for memory formation and storage disrupted dendrites can contribute to AD Diets are critical for health and are easily modifiable factor Several epidemiologic and animal studies have revealed correlations between metabolic disorders including obesity and neurodegenerative diseases Our second study aimed to assess the effect of diet-induced obesity on Parkinson’s disease (PD) with emphasis on the dopaminergic pathway and brain peroxisome proliferator-activated receptors (PPARs) In mice a high-fat diet (HFD) resulted in fewer dopaminergic neurons in the substantia nigra (SN) HFD also induced neuroinflammation with increased astrogliosis in the SN and striatum Dendritic spine density in the SN of HFD-exposed mice decreased which suggested that prolonged HFD altered dopaminergic neuroplasticity All three PPAR subtype (PPAR-? PPAR-β/δ PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area (VTA) of HFD mice when compared to those in normal-diet controls and the PPAR-? showed the most prominent reduction

Date of Award	2020
Original language	English
Supervisor	Kuen-Jer Tsai (Supervisor)