Effects of aerobic exercise on adult hippocampal neurogenesis in Alzheimer’s disease mice

doi:10.12307/2024.131

Abstract

Abstract: BACKGROUND: Exercise improves Alzheimer’s disease, dementia, and age-related cognitive abilities. A potential mediator between exercise and these health benefits may be adult hippocampal neurogenesis. Therefore, it is of great significance to explore whether and how exercise affects the adult hippocampal neurogenesis process in Alzheimer’s disease mice.
OBJECTIVE: To observe the effect of aerobic exercise on adult hippocampal neurogenesis of Alzheimer’s disease mice, and to explore whether aerobic exercise can promote their adult hippocampal neurogenesis.
METHODS: Three-month-old wild-type (C57BL/6Jnju) and APP/PS1 double transgenic Alzheimer’s disease mice were randomly divided into four groups: wild control group, wild exercise group, Alzheimer’s disease control group and Alzheimer’s disease exercise group, with 20 mice in each group. The control group did not do exercise, and the exercise group did aerobic exercise for 5 months. After exercise intervention, real-time PCR, immunofluorescence and western blot assay were used to detect the expression levels of DCX, Ki67, βIII-tubulin and NeuN in the hippocampal tissue of mice in each group.
RESULTS AND CONCLUSION: The expressions of DCX, βIII-tubulin and NeuN in the hippocampal dentate gyrus in the Alzheimer’s disease control group were significantly lower than those in the wild control group (P < 0.05). The expressions of DCX, Ki67, βIII-tubulin and NeuN were significantly higher in the hippocampal dentate gyrus in the Alzheimer’s disease exercise group than those in the Alzheimer’s disease control group (P < 0.05). It is indicated that long-term aerobic exercise intervention can strengthen the proliferation, migration and differentiation of neurons during adult hippocampal neurogenesis and significantly increase the number of neuronal precursor cells and new neurons in Alzheimer’s disease mice.

Key words: Alzheimer’s disease, aerobic exercise, learning and memory ability, adult hippocampal neurogenesis

CLC Number:

Zhang Yeting, Li Chuikun, Wei Cuilan, Fu Yan, Zhang Feifei. Effects of aerobic exercise on adult hippocampal neurogenesis in Alzheimer’s disease mice[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(13): 2068-2075.

Figures/Tables 12

References

[1] GAGE FH. Mammalian neural stem cells. Science. 2000;287(5457): 1433-1438.
[2] BOLDRINI M, FULMORE CA, TARTT AN, et al. Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell. 2018;22(4): 589-599.e5.
[3] AUGUSTO-OLIVEIRA M, ARRIFANO GPF, MALVA JO, et al. Adult Hippocampal Neurogenesis in Different Taxonomic Groups: Possible Functional Similarities and Striking Controversies. Cells. 2019;8(2):125.
[4] JESSBERGER S, CLARK RE, BROADBENT NJ, et al. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem. 2009;16(2):147-154.
[5] DAHLIN E, ANDERSSON M, THORÉN A, et al. Effects of physical exercise and stress on hippocampal CA1 and dentate gyrus synaptic transmission and long-term potentiation in adolescent and adult Wistar rats. Neuroscience. 2019;408:22-30.
[6] ZHANG C, MCNEIL E, DRESSLER L, et al. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp Neurol. 2007;204(1):77-87.
[7] VOSS MW, HEO S, PRAKASH RS, et al. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention. Hum Brain Mapp. 2013;34(11):2972-2985.
[8] LAUTENSCHLAGER NT, COX KL, ELLIS KA. Physical activity for cognitive health: what advice can we give to older adults with subjective cognitive decline and mild cognitive impairment? Dialogues Clin Neurosci. 2019;21(1):61-68.
[9] 张象,张业廷.运动改善阿尔茨海默症模型小鼠病程的剂量效应关系[J].中国组织工程研究,2021,25(17):2761-2766.
[10] VERMUNT L, SIKKES SAM, VAN DEN HOUT A, et al. Duration of preclinical, prodromal, and dementia stages of Alzheimer’s disease in relation to age, sex, and APOE genotype. Alzheimers Dement. 2019;15(7):888-898.
[11] MONTGOMERY W, GOREN A, KAHLE-WROBLESKI K, et al. Detection, diagnosis, and treatment of Alzheimer’s disease dementia stratified by severity as reported by caregivers in Japan. Neuropsychiatr Dis Treat. 2018;14:1843-1854.
[12] HOFFMANN K, SOBOL NA, FREDERIKSEN KS, et al. Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial. J Alzheimers Dis. 2016;50(2):443-453.
[13] TOLPPANEN AM, SOLOMON A, KULMALA J, et al. Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia. Alzheimers Dement. 2015;11(4):434-443.e6.
[14] SOFI F, VALECCHI D, BACCI D, et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med. 2011;269(1):107-117.
[15] PANZA GA, TAYLOR BA, MACDONALD HV, et al. Can Exercise Improve Cognitive Symptoms of Alzheimer’s Disease? J Am Geriatr Soc. 2018; 66(3):487-495.
[16] 赵祥,魏翠兰,张业廷.神经发生和炎性环境在运动条件下的改变与调节[J].中国组织工程研究,2021,25(5):813-820.
[17] JU Y, TAM KY. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regen Res. 2022;17(3):543-549.
[18] YANG X, YAO C, TIAN T, et al. A novel mechanism of memory loss in Alzheimer’s disease mice via the degeneration of entorhinal-CA1 synapses. Mol Psychiatry. 2018;23(2):199-210.
[19] MORENO-JIMÉNEZ EP, FLOR-GARCÍA M, TERREROS-RONCAL J, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25(4):554-560.
[20] TOBIN MK, MUSARACA K, DISOUKY A, et al. Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients. Cell Stem Cell. 2019;24(6):974-982.e3.
[21] LEI X, WU Y, XU M, et al. Physical exercise: bulking up neurogenesis in human adults. Cell Biosci. 2019;9:74.
[22] VAN PRAAG H, KEMPERMANN G, GAGE FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999;2(3):266-270.
[23] VAN PRAAG H, CHRISTIE BR, SEJNOWSKI TJ, et al. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96(23):13427-13431.
[24] CASSILHAS RC, TUFIK S, DE MELLO MT. Physical exercise, neuroplasticity, spatial learning and memory. Cell Mol Life Sci. 2016;73(5):975-983.
[25] 孙开宏,王坤.运动对应激的保护效应与成年神经发生的关系[J].中国康复医学杂志,2018,33(11):1374-1377.
[26] LIANG YY, ZHANG LD, LUO X, et al. All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease. Neural Regen Res. 2022;17(6):1210-1227.
[27] CLARK PJ, BRZEZINSKA WJ, THOMAS MW, et al. Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice. Neuroscience. 2008;155(4):1048-1058.
[28] CHOI SH, BYLYKBASHI E, CHATILA ZK, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science. 2018;361(6406):eaan8821.
[29] LAFENÊTRE P, LESKE O, MA-HÖGEMEIE Z, et al. Exercise can rescue recognition memory impairment in a model with reduced adult hippocampal neurogenesis. Front Behav Neurosci. 2010;3:34.
[30] PEREIRA AC, HUDDLESTON DE, BRICKMAN AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007;104(13):5638-5643.
[31] GRIFFIN ÉW, MULLALLY S, FOLEY C, et al. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiol Behav. 2011;104(5):934-941.
[32] SZYMURA J, KUBICA J, WIECEK M, et al. The Immunomodulary Effects of Systematic Exercise in Older Adults and People with Parkinson’s Disease. J Clin Med. 2020;9(1):184.
[33] ERICKSON KI, VOSS MW, PRAKASH RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-3022.
[34] CHAPMAN SB, ASLAN S, SPENCE JS, et al. Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Front Aging Neurosci. 2013;5:75.
[35] YANG C, MOORE A, MPOFU E, et al. Effectiveness of Combined Cognitive and Physical Interventions to Enhance Functioning in Older Adults With Mild Cognitive Impairment: A Systematic Review of Randomized Controlled Trials. Gerontologist. 2020;60(8):633-642.