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Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
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Time-of-day effects on post-exercise phosphoproteomic profiling in mouse hippocampus.

Ping Qian1,2, Jinying Shen1,3, Fangming Wang4

  • 1Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.

Frontiers in Cell and Developmental Biology
|April 8, 2026
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Summary
This summary is machine-generated.

Timed exercise impacts the hippocampus differently depending on the time of day. Daytime exercise may enhance learning, while nighttime exercise might reduce neuroinflammation, affecting key signaling pathways.

Keywords:
acute exercisecircadian rhythmhippocampusphosphorylationsynapse

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Area of Science:

  • Exercise physiology
  • Chronobiology
  • Neuroscience

Background:

  • Exercise offers cognitive benefits, but optimal timing for maximal physiological outcomes is under investigation.
  • The influence of exercise timing on hippocampal function and signaling pathways remains largely unexplored.

Purpose of the Study:

  • To investigate the effects of exercise timing on hippocampal phosphoproteomic profiling.
  • To identify time-dependent changes in protein phosphorylation within the hippocampus following acute exercise.

Main Methods:

  • Hippocampal phosphoproteomic profiling using affinity enrichment and liquid chromatography-tandem mass spectrometry in mice.
  • Exercise or sham-exercise performed during the early rest (ZT3) or early active (ZT15) phase.
  • Bioinformatic analyses including functional enrichment, motif analysis, and kinase prediction to compare phase-specific exercise effects.

Main Results:

  • Acute exercise induced significant changes in 932 phosphosites (rest phase) and 828 phosphosites (active phase), with only 49 overlapping sites.
  • Functional enrichment revealed broader signaling pathway modulation by exercise during the rest phase (ZT3).
  • Both exercise timings converged on glutamate synapse-calcium signaling-LTP pathways, with distinct molecular nodes; daytime exercise increased pCaMKII/CaMKII, while nighttime exercise suppressed GFAP and IBA1.

Conclusions:

  • Timed exercise elicits time-dependent phosphoproteomic features in the hippocampus.
  • Early daytime exercise may support hippocampus-dependent learning, whereas early nighttime exercise may reduce neuroinflammation.
  • This study provides insights into the circadian regulation of hippocampal exercise physiology.