eng Rovedar Journal of Lab Animal Research 2980-9703 2026-04-30 5 2 21 28 10.58803/jlar.v5i2.105 115 Ali Heydari 0 https://orcid.org/0009-0003-4806-082X Shayan Amini 1 https://orcid.org/0009-0005-9915-0627 Ali Mobaraki 1 https://orcid.org/0009-0007-2371-3969 Marzieh Saki 2 https://orcid.org/0009-0007-9897-9673 Narges Safari 3 https://orcid.org/0009-0007-0672-1035 Diana Abbasi 4 https://orcid.org/0009-0004-6969-5143 Mohammadreza Dana 5 https://orcid.org/0009-0005-6541-6386 Department of Clinical Sciences, Faculty of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran Shahid Beheshti Medical University, Tehran, Iran Faculty of Veterinary Medicine, Islamic Azad University, Shoushtar Branch, Shoushtar, Iran Department of Veterinary Medicine, Islamic Azad University, Garmsar Branch, Garmsar, Iran Department of Clinical Sciences, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran Introduction: Exercise training with antioxidant and anti-inflammatory supplements plays an effective role in dementia progression, and tryptophan is an essential amino acid that can be supplied through the diet. The present study aimed to investigate the effects of treadmill exercise and tryptophan supplementation on brain antioxidant levels, synapsin 1 (SYN1), brain-derived neurotrophic factor (BDNF), and postsynaptic density-95 (PSD-95) mRNA in rats fed a high‑fat diet (HFD). Materials and methods: A total of 75 male rats, 2-3 months old, with an average weight of 527 grams, were randomly assigned to five groups, with five rats per group and three replicates. The first group was administered the standard low-fat diet daily (LF), the second group was administered the HFD daily (HF), the third group was administered the HFD along with a tryptophan supplement at 250 mg/kg/orally (HFTS), the fourth group was given the HFD along with the tryptophan supplement and exercised daily (HFETS), and the fifth group was fed the HFD only and exercised (HFE). Exercise training was performed on a rodent treadmill, three days/week for eight weeks. At the end of the exercise protocol and cognitive analyses (light/dark maze and Barnes maze), rats were euthanized, and brain tissue was collected for real-time polymerase chain reaction analysis of brain antioxidant, SYN1, BDNF, and PSD-95 mRNA. Results: The HFD significantly raised serum total cholesterol and triglycerides compared to the low-fat diet, while the HFETS group reduced cholesterol to levels similar to the LF group. In the Barnes maze test, the HFETS group demonstrated the shortest escape time and fewest errors, indicating improved spatial learning, whereas no differences in anxiety-like behavior were observed in the light/dark maze analysis. Additionally, HFE and HFETS groups exhibited higher catalase levels and restored hippocampal PSD-95 expression, while SYN1 expression was increased in all HFD-fed groups compared to the LF group. BDNF expression did not differ significantly across all groups. Conclusion: In aged rats, combining exercise with tryptophan supplementation partially mitigated HFD‑induced metabolic disturbances and improved spatial learning and memory. Exercise alone was more effective than tryptophan supplementation in preventing the adverse effects of an HDF during aging. https://jlar.rovedar.com/index.php/JLAR/article/view/105 Aging Exercise training High-fat diet Memory Tryptophan