Changes in the hippocampal level of tau but not beta-amyloid may mediate anxiety-like behavior improvement ensuing from exercise in diabetic female rats

Behav Brain Funct. 2024 May 3;20(1):9. doi: 10.1186/s12993-024-00235-0.


Background: In the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes.

Methods: Twenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80-100% of VMax, 4-10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot.

Results: An increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM.

Conclusions: HIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau.

Keywords: Cognitive function; High-intensity interval training; Learning; Memory; Type 2 diabetes.

MeSH terms

  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Anxiety* / metabolism
  • Anxiety* / psychology
  • Anxiety* / therapy
  • Behavior, Animal / physiology
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / psychology
  • Diabetes Mellitus, Experimental* / therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / psychology
  • Diabetes Mellitus, Type 2 / therapy
  • Diet, High-Fat / adverse effects
  • Female
  • High-Intensity Interval Training / methods
  • Hippocampus* / metabolism
  • Maze Learning / physiology
  • Physical Conditioning, Animal* / methods
  • Physical Conditioning, Animal* / physiology
  • Physical Conditioning, Animal* / psychology
  • Rats
  • Rats, Sprague-Dawley
  • tau Proteins* / metabolism


  • tau Proteins
  • Amyloid beta-Peptides