Time-restricted feeding modulates neuron-glial interactions and circadian rhythm in the spinal cord of male Wistar rats fed a high-fat diet

STUDY DESIGN: This study utilized male Wistar rats to investigate the effects of time-restricted feeding (TRF) on high-fat diet (HFD)-induced alterations in neuron-glial interactions and gene expression levels in the spinal cord (T5-T9).

OBJECTIVES: To evaluate whether TRF mitigates HFD-induced alterations in microglial morphology, astrocyte numbers, perineuronal net (PNN) integrity, purinergic receptor expression, inflammation and circadian rhythm-related gene expression in the spinal cord.

SETTING: Amsterdam University Medical Centers, location AMC, The Netherlands.

METHODS: Male Wistar rats were initially fed either a standard chow diet or a HFD ad libitum for 4 weeks. After this period, rats in the HFD group were further divided into two subgroups: continued HFD ad libitum or HFD with TRF for an additional 4 weeks. Rats in the chow group continued with ad libitum feeding throughout the experimental period. At the end of the intervention, spinal cords (T5-T9) were collected for analysis. Microglial morphology, astrocyte cell numbers, and PNN integrity were assessed in the spinal cord. Expression levels of purinergic receptors, inflammation and clock genes were analyzed to investigate neuron-glial interactions and circadian rhythm stabilization.

RESULTS: TRF reduced microglial activation, preserved PNN integrity, suppressed HFD-induced upregulation of purinergic receptors, and stabilized circadian clock gene expression.

CONCLUSIONS: These findings suggest that TRF is a promising non-pharmacological strategy to counteract obesogenic diet-induced perineuronal net degradation and neuroinflammation, highlighting its potential as a lifestyle-based intervention for pain management.