Research Projects

Prolonged rapid eye movement (REM) sleep deprivation (REMSD) has been linked to neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Fronto-temporal dementia (FTD). Modern lifestyles adversely affect sleep behavior and pattern, leading to increased levels of noradrenaline (NA), a neurotransmitter, and alterations in RNA-binding proteins (RBPs). The aggregate formation mediated by low-complexity domains of RBPs is critical for their involvement in neuronal degeneration. In ALS, cytoplasmic and nuclear inclusions of TDP-43 are the pathological hallmarks of the disease. Disease-linked mutations in RBPs, such as in FUS and hnRNPA1, promote the accumulation of insoluble fibrils, leading to pathological amyloids. The REM sleep behavioral disorder has been observed in few ALS patients, reflecting the neurodegeneration of CNS pathways involved in REM sleep regulation. The present study aims to understand the role of RBPs during REM sleep deprivation and decipher their cross-talk during the development of neurodegenerative disorders. The study will analyze changes in RBPs (particularly TDP-43, FUS, TIA1) in different regions of the rat brain during REM sleep deprivation at RNA and protein levels using quantitative RT-PCR and immunoblotting. Additionally, PC12 neuronal cell culture expressing TDP-43 protein will be investigated for changes in the distribution of this RBP when treated with NA and GABA. This study has significant implications for public health, particularly for night shift workers and those who stretch working hours at the cost of sleeping time.

0