INFLUENCE OF CIRCADIAN RHYTHM ON SYNAPTIC PLASTICITY IN NEURODEGENERATIVE DISORDERS.

Purpose and Background This research explores how disruptions in the circadian rhythm influence synaptic plasticity and contribute to the onset and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The project is grounded in the understanding that the circadian rhythm — governed by genes like BMAL1, CLOCK, PER, and CRY — regulates critical biological functions, including neuronal activity, energy metabolism, and hormonal cycles. When this rhythm becomes desynchronized (due to aging, artificial light exposure, or sleep disorders), it leads to oxidative stress, inflammation, and impaired neuronal repair mechanisms. These disturbances play a key role in the degeneration of neurons and cognitive decline. Research Objectives The main goal is to synthesize and analyze scientific evidence from 2020–2025 that demonstrates how circadian rhythm disruption affects neuroplasticity, accelerates neurodegeneration, and identifies therapeutic strategies capable of restoring biological synchronization to protect neuronal function. Methodology A systematic exploratory review (scoping review) was conducted across databases such as PubMed, Scopus, Web of Science, Cochrane Library, and SciELO. Studies included involved human or animal models with neurodegenerative diseases, focusing on circadian dysregulation and synaptic plasticity. Selection followed PRISMA guidelines, resulting in 25 key studies analyzed qualitatively through thematic synthesis. Main Findings The review revealed that: • Loss of synchrony in core clock genes (BMAL1, CLOCK) disrupts neuronal metabolism, increases neuroinflammation, and decreases BDNF (brain-derived neurotrophic factor), impairing synaptic repair and learning capacity. • Chronic circadian disruption leads to sustained oxidative stress and inflammatory activity, promoting accumulation of toxic proteins like β-amyloid and α-synuclein, hallmarks of Alzheimer’s and Parkinson’s. • Sleep-wake cycle fragmentation appears as an early biomarker of neurodegeneration, preceding cognitive symptoms. • Therapeutic interventions such as light therapy, melatonin supplementation, and sleep regulation show promise in restoring circadian synchrony, improving neuroplasticity, and slowing disease progression. Expected Outcomes This project aims to establish the circadian rhythm as an independent pathophysiological factor and therapeutic target in neurodegenerative diseases. Expected outcomes include: • Identification of molecular mechanisms linking circadian dysregulation with synaptic dysfunction. • Proposal of chronobiological interventions to complement neuroprotective therapies. • Recommendations for clinical protocols to detect and manage circadian disruption in patients with neurodegenerative conditions. • Guidance for future research to define biomarkers predicting neuroplastic deterioration due to circadian misalignment. Significance By integrating molecular neuroscience, chronobiology, and clinical neurology, this research provides a comprehensive framework for understanding how maintaining circadian homeostasis can preserve neuronal plasticity and cognitive function. Ultimately, it advocates for a multidisciplinary therapeutic model combining circadian regulation with traditional neuroprotective treatments to improve patients’ quality of life.