Time‐Restricted Feeding Preserves Synaptic Function and Modulates Reelin and α ‐Synuclein in an Acute Amyloid‐ β Rat Model: A Comparative Study With Alternate‐Day Fasting

Introduction Alzheimer’s disease (AD), a major neurodegenerative disorder, is characterized by progressive cognitive decline and the accumulation of amyloid‐beta and tau proteins in the brain. Intermittent fasting (IF) is being explored as a dietary intervention to mitigate AD‐related effects, possibly by modulating factors such as reelin and α ‐synuclein, which are involved in synaptic function and AD pathology. Methods The study included six groups of rats: Ctrl, Ctrl.ADF, Ctrl.TRF, AD, AD.TRF, and AD.ADF. AD was induced by bilateral ICV injections of 5 μL Aβ. To prove fasting, blood glucose levels were assessed with a glucometer. Memory and learning were assessed using the Morris Water Maze (MWM) test, and hippocampal reelin and α ‐synuclein concentrations were quantified via ELISA. Electrophysiological recordings were analyzed using eProbe software. Results TRF was more effective than ADF in improving cognitive function in AD rats, as indicated by a significant increase in TSGQ [ F (5,40) = 5.590, p < 0.01] and swimming speed [ F (3,21) = 114.3, p < 0.01], along with a significant reduction in latency time and path length ( p < 0.001). Both TRF and ADF significantly increased reelin concentration and neuronal firing rate ( p < 0.01), whereas only TRF led to a significant decrease in α ‐synuclein levels. Discussion These findings suggest that TRF may enhance spatial memory and reduce α ‐synuclein accumulation in AD rats, possibly through mechanisms associated with synaptic plasticity and neuroprotection.