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

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...

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Main Authors: Zhou Lei, Soroosh Mozaffaritabar, Takuji Kawamura, Atsuko Koike, Attila Kolonics, Johanna Kéringer, Ricardo A. Pinho, Jingquan Sun, Ruonan Shangguan, Zsolt Radák
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024004523
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author Zhou Lei
Soroosh Mozaffaritabar
Takuji Kawamura
Atsuko Koike
Attila Kolonics
Johanna Kéringer
Ricardo A. Pinho
Jingquan Sun
Ruonan Shangguan
Zsolt Radák
author_facet Zhou Lei
Soroosh Mozaffaritabar
Takuji Kawamura
Atsuko Koike
Attila Kolonics
Johanna Kéringer
Ricardo A. Pinho
Jingquan Sun
Ruonan Shangguan
Zsolt Radák
author_sort Zhou Lei
collection DOAJ
description 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.
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spelling doaj.art-f317b18ae231462f97ddbcf825573af72024-02-03T06:37:22ZengElsevierHeliyon2405-84402024-01-01102e24421The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged miceZhou Lei0Soroosh Mozaffaritabar1Takuji Kawamura2Atsuko Koike3Attila Kolonics4Johanna Kéringer5Ricardo A. Pinho6Jingquan Sun7Ruonan Shangguan8Zsolt Radák9Research Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, HungaryResearch Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, HungaryResearch Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, Hungary; Waseda Institute for Sport Sciences, Waseda University, Saitama, 359-1192, JapanDepartment of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, 153–8902, JapanResearch Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, HungaryResearch Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, HungaryLaboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, 80215-901, BrazilInstitute of Sports Science, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, ChinaDepartment of Physical Education, Chengdu University, 610106, Chengdu, ChinaResearch 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; Corresponding author. Research Institute of Molecular Exercise Science, Hungarian University of Sports Science, H-1123, Budapest, Hungary.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.http://www.sciencedirect.com/science/article/pii/S2405844024004523LactateExerciseAgingBrain functionLactylationHippocampus
spellingShingle Zhou Lei
Soroosh Mozaffaritabar
Takuji Kawamura
Atsuko Koike
Attila Kolonics
Johanna Kéringer
Ricardo A. Pinho
Jingquan Sun
Ruonan Shangguan
Zsolt Radák
The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
Heliyon
Lactate
Exercise
Aging
Brain function
Lactylation
Hippocampus
title The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
title_full The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
title_fullStr The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
title_full_unstemmed The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
title_short The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice
title_sort effects of long term lactate and high intensity interval training hiit on brain neuroplasticity of aged mice
topic Lactate
Exercise
Aging
Brain function
Lactylation
Hippocampus
url http://www.sciencedirect.com/science/article/pii/S2405844024004523
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