Time-restricted feeding improves cognitive function in Alzheimer's mice through GCK/NPY/apoptosis pathway

Area of Science:

• Neuroscience
• Metabolic Disorders
• Chronobiology

Background:

• Alzheimer's disease (AD) involves cognitive decline, neuronal loss, and disrupted circadian rhythms.
• Time-restricted feeding (TRF) aligns eating with circadian rhythms, showing potential for neurodegenerative disorders.

Purpose of the Study:

• To investigate the effects of TRF on cognitive function and neuronal apoptosis in AD mouse models.
• To elucidate the role of the GCK/NPY/apoptosis pathway in TRF's therapeutic mechanisms for AD.

Main Methods:

• APP/PS1/Tau transgenic mice and wild-type mice were subjected to ad libitum (AL) or TRF for 3 months.
• Cognitive performance was assessed using behavioral tests; hippocampal tissues were analyzed via Western blot, qPCR, and Nissl staining.
• In vitro studies used HT22 cells treated with Aβ and siGCK to examine the GCK/NPY/apoptosis pathway.

Main Results:

• TRF reduced food intake, weight gain, p-Tau accumulation, and hippocampal neuronal apoptosis in AD mice.
• TRF improved cognitive function and restored the GCK/NPY pathway.
• Silencing GCK in vitro reduced p-Tau and apoptosis, while increasing NPY, with recurrence upon GCK re-silencing.

Conclusions:

• TRF enhances cognitive function and mitigates neuronal apoptosis in AD mouse models.
• Modulation of the GCK/NPY pathway is a key mechanism underlying TRF's benefits in AD.
• TRF represents a potential non-pharmacological intervention for Alzheimer's disease.