High-intensity interval training (HIIT) and lactate protect against sleep deprivation-induced memory impairment: Role of the PKA-CREB-BDNF-Cofilin signaling pathway

Physiol Behav. 2025 Nov 1:301:115076. doi: 10.1016/j.physbeh.2025.115076. Epub 2025 Aug 22.

Abstract

Background: The present study aims to investigate the protective effect of high-intensity interval training (HIIT) or lactate administration on signaling pathway (Protein kinase A (PKA)/ Cyclic AMP response element-binding (CREB)/ Brain-derived neurotrophic factor (BDNF)/ P-cofilin) associated with memory impairment in hippocampal tissue due to sleep deprivation (SD).

Material and methods: 42 male Wistar rats were randomly divided into six groups: 1. Control, 2. SD, 3. SD + HIIT, 4. HIIT, 5. Lactate, 6. SD + Lactate. Training groups participated in 6 weeks of HIIT on a treadmill and lactate groups received a daily dose of lactate intraperitoneally for 6 weeks (Target concentration of lactate was 7 ± 0.7 mmol/L). After 6 weeks of treatment, SD groups were placed in a water-based sleep deprivation device for 48 h. Spatial memory was assessed by Morris water maze (MWM). Proteins (PKA/BDNF/P-cofilin) and gene (CREB) expression were measured by Western blot analysis and Real-Time PCR (2-ΔΔCT), respectively.

Results: After 6 weeks, there was a significant increase in number of enter in target zone (P = 0.001), time in target zone (P = 0.002) and path length (P = 0.03) between HIIT and control group. SD significantly decreased BDNF (P < 0.0001), PKA (P < 0.0001) and p-cofilin (P < 0.0001) protein expression in hippocampus tissue, compared with control group.

Conclusion: HIIT and lactate can improve the spatial memory in SD condition. It seems that many adaptations resulting from HIIT are associated with increased lactate levels as a crucial signaling molecule in the hippocampus.

Keywords: BDNF; HIIT; Lactate; P-cofilin; PKA; Sleep deprivation.

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • High-Intensity Interval Training* / methods
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lactic Acid* / pharmacology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders* / etiology
  • Memory Disorders* / metabolism
  • Memory Disorders* / prevention & control
  • Memory Disorders* / therapy
  • Rats
  • Rats, Wistar
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology
  • Sleep Deprivation* / complications
  • Sleep Deprivation* / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases
  • Lactic Acid
  • Bdnf protein, rat
  • Actin Depolymerizing Factors
  • Creb1 protein, rat