Title : The role of the circadian rhythm in alzheimer's disease and aging
Abstract:
During the course of evolution and earth’s rotation round its axis, the surface inhabitants are exposed to daily a predictable light and dark condition which impose specific demands on the physiology and influences the behaviour of an organism. Such cyclic patterns in the physiological activity (known as biological rhythms) showing recurrence of 24 hours (i.e. 24h periodicity) are called circadian rhythms. These rhythms are maintained by circadian clocks existing in every cell of an organism and influence every physiological activity in the system. Aging is a natural, universal, unidirectional, and inevitable process which leads to compromised and progressive decline in all the physiological functions including the circadian timing system (CTS). Alzheimer’s disease (AD) is an age associated most common neurodegenerative disorder linked to reduced neuronal regeneration and compromised cognitive abilities, learning and memory functioning. Researchers have found that circadian disturbance in the form of disrupted sleep-wake cycles frequently happen early in the AD and may even happen before cognitive symptoms appear and hence suggest a possible link between circadian clock and AD. Additionally, the pathogenic amyloid-beta peptide levels in the brain seem to be regulated by the sleep-wake cycle, and modifying sleep can affect AD-related pathology in various animal models through a variety of pathways. Since AD is a disease of dementia and the glutamate mediated signalling pathway forms the basis of learning and memory formation, hence our focus was to study the rhythmic expression of two most common glutamate receptors, Nmda and Ampa in both aging and AD conditions. We have also studied 5 other molecular components (genes) supposed to be involved in learning and memory including Reln, Dlg3, Dlg4, Creb1, and Creb2. Our results have highlighted the importance of circadian component involved in signalling pathway of learning and memory, its disruption upon aging and AD induction. From our results, we have also hypothesised a possible mechanism involving 5 molecules along with Nmda and Ampa in the signalling pathway of learning and memory. Our results also highlight the importance of circadian clock disruptions observed during early stages of AD progression represented by deposition of Amyloid beta (Aβ) plagues without involving neurofibrillary tangles (NFTs).
Audience Take Away Notes:
- What is a circadian clock?
- How does circadian clock works in mammalian system?
- How important is circadian clock in maintaining the phyiology?
- Is there a need to keep a track of daily activities of a person to achieve healthy aging?
