Time-Restricted Feeding Preserves Synaptic Function and Modulates Reelin and α-Synuclein in an Acute Amyloid-β Rat...

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.

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.

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.

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.