Lei Zhou, Mozaffaritabar Soroosh, Kawamura Takuji, Koike Atsuko, Kolonics Attila, Kéringer Johanna, Pinho Ricardo A, Sun Jingquan, Shangguan Ruonan, Radák Zsolt
Research Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, Hungary.
Waseda Institute for Sport Sciences, Waseda University, Saitama, 359-1192, Japan.
Heliyon. 2024 Jan 10;10(2):e24421. doi: 10.1016/j.heliyon.2024.e24421. eCollection 2024 Jan 30.
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.
广泛的研究证实了运动对促进大脑健康有诸多益处。最近的研究提出了运动副产品乳酸在大脑功能和疾病的各个方面的潜在益处。然而，在理解乳酸剂量的影响及其对老年啮齿动物的作用方面仍存在差距。本研究首先作为第一个实验，考察了三种不同剂量的乳酸干预（2000毫克/千克、1000毫克/千克和500毫克/千克）和高强度间歇训练（HIIT）对衰老小鼠（20 - 22个月）的长期影响。随后，在第二个实验中，我们研究了500毫克/千克乳酸干预和HIIT对老年小鼠（25 - 27个月）大脑神经可塑性的长期影响。第一个实验的结果表明，HIIT和不同剂量的乳酸干预（500毫克/千克和2000毫克/千克）均对衰老小鼠海马体中的神经可塑性生物标志物VEGF产生了积极影响。随后，第二个实验表明，长期的HIIT显著改善了小鼠在旷场、新物体识别和被动回避测试中的表现。然而，乳酸干预并未对这些行为测试产生显著影响。此外，与对照组相比，HIIT和乳酸干预均对老年小鼠海马体中的血管生成信号通路（p/t - AKT/ENOS/VEGF）、线粒体生物标志物（SDHA）和代谢蛋白（p/t - CREB、p/t - HSL和LDH）产生了积极影响。值得注意的是，只有乳酸干预显著提高了BDNF（PGC - 1α、SIRT1和BDNF）信号通路和代谢含量（乳酸和丙酮酸）。最后，长期的HIIT和乳酸干预未能改变老年小鼠海马体中p/t - mTOR、iNOS、nNOS、HIF - 1α、SYNAPSIN、SIRT3、NAMPT、CS、FNDC5和泛乳酸 - 赖氨酸的蛋白表达。总之，本研究证明长期的HIIT和乳酸治疗对老年小鼠的大脑功能有积极影响，表明乳酸作为一种治疗策略在老年人群神经退行性疾病中的潜在应用价值。
