The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice

Zhou Lei; Soroosh Mozaffaritabar; Takuji Kawamura; Atsuko Koike; Attila Kolonics; Johanna Kéringer; Ricardo A Pinho; Jingquan Sun; Ruonan Shangguan; Zsolt Radák

doi:10.1016/j.heliyon.2024.e24421

The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice

Heliyon. 2024 Jan 10;10(2):e24421. doi: 10.1016/j.heliyon.2024.e24421. eCollection 2024 Jan 30.

Authors

Zhou Lei¹, Soroosh Mozaffaritabar¹, Takuji Kawamura^{1

2}, Atsuko Koike³, Attila Kolonics¹, Johanna Kéringer¹, Ricardo A Pinho⁴, Jingquan Sun⁵, Ruonan Shangguan⁶, Zsolt Radák^{1

2}

Affiliations

¹ Research Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, Hungary.
² Waseda Institute for Sport Sciences, Waseda University, Saitama, 359-1192, Japan.
³ Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, 153-8902, Japan.
⁴ Laboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, 80215-901, Brazil.
⁵ Institute of Sports Science, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, China.
⁶ Department of Physical Education, Chengdu University, 610106, Chengdu, China.

Abstract

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20-22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25-27 months). The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice. In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.

Keywords: Aging; Brain function; Exercise; Hippocampus; Lactate; Lactylation.