The neuroprotective effects of caffeine on the mice model of Parkinson’s disease: a transcriptomic analysis
Zheng Yuyin1, Feng Yijia2, Ruan Qingqing2, Tu Wenzhan1
1.Department of Rehabilitation Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China; 2.Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
Zheng Yuyin,Feng Yijia,Ruan Qingqing, et al. The neuroprotective effects of caffeine on the mice model of Parkinson’s disease: a transcriptomic analysis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2021, 51(6): 444-448,453.
Abstract:Objective: To investigate by transcriptomics the possible molecular mechanism of the protective effect of caffeine in Parkinson’s disease, so as to provide new evidence for elucidating the neuroprotective effect of caffeine. Methods: The mice were injected with α-synuclein (α-Syn) fibril in the hippocampal region by stereotaxic injection, and were fed with caffeine. Three months later, the hippocampus tissues were isolated for transcriptome sequencing (RNA-seq). Results: α-synuclein was obviously aggregated in hippocampus and impaired the working memory in mice (P<0.05). Long-term drinking caffeine could effectively improve the cognitive impairment caused by α-Synuclein in mice (P<0.05). The transcriptome changes induced by α-Synuclein were mainly enriched in the pathways of microglial activation and chemokines signaling. Chronic caffeine consumption significantly improved the cell proliferation (P<0.05). Conclusion: Caffeine may repair the neuronal inflammatory damage caused by α-Syn via promoting cell proliferation.
参考文献:
[1] GOEDERT M. Alpha-synuclein and neurodegenerative diseases[J]. Nat Rev Neurosci, 2001, 2(7): 492-501.
[2] GOUD K Y, MOONLA C, MISHRA R K, et al. Wearable electrochemical microneedle sensor for continuous monitoring of levodopa: toward parkinson management[J]. ACS Sens, 2019, 4(8): 2196-2204.
[3] HAVELUND J F, ANDERSEN A D, BINZER M, et al. Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia[J]. J Neurochem, 2017, 142(5): 756-766.
[4] YOOSEFIAN M, RAHMANIFAR E, ETMINAN N. Nanocarrier for levodopa Parkinson therapeutic drug; comprehensive benserazide analysis[J]. Artif Cells Nanomed Biotechnol, 2018, 46(sup1): 434-446.
[5] GROSSO G, GODOS J, GALVANO F, et al. Coffee, caffeine, and health outcomes: An umbrella review[J]. Annu Rev Nutr, 2017, 37: 131-156.
[6] HIGDON J V, FREI B. Coffee and health: a review of recent human research[J]. Crit Rev Food Sci Nutr, 2006, 46(2): 101-123.
[7] COSTENLA A R, CUNHA R A, Mendonça A D. Caffeine, adenosine receptors, and synaptic plasticity[J]. J Alzheimers Dis, 2010, 20 Suppl 1: S25-S34.
[8] LUAN Y, REN X, ZHENG W, et al. Chronic caffeine treatment protects against alpha-synucleinopathy by reestablishing autophagy activity in the mouse striatum[J]. Front Neurosci, 2018, 12: 301.
[9] HU Q, REN X, LIU Y, et al. Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy [J]. Exp Neurol, 2016, 283(Pt A): 213-223.
[10] ZHENG W, ZHOU J, LUAN Y, et al. Spatiotemporal control of GPR37 signaling and its behavioral effects by optogenetics [J]. Front Mol Neurosci, 2018, 11: 95.
[11] VOLPICELLI-DALEY L A, LUK K C, PATEL T P, et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death [J]. Neuron, 2011, 72(1): 57-71.
[12] LUK K C, KEHM V M, ZHANG B, et al. Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice[J]. J Exp Med, 2012, 209(5): 975-986.
[13] LUK K C, KEHM V K, CARROLL J, et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice[J]. Science, 2012, 338(6109): 949-953.
[14] SONG N, CHEN L, XIE J. Alpha-synuclein handling by microglia: activating, combating, and worsening[J]. Neurosci Bull, 2021, 37(5): 751-753.
[15] CHENG B, LI X, DAI K, et al. Triggering receptor expressed on myeloid cells-2 (TREM2) interacts with colony-stimulating factor 1 receptor (CSF1R) but is not necessary for CSF1/CSF1R-mediated microglial survival[J]. Front Immunol, 2021, 12: 633796.
[16] WANG C, XIONG M, GRATUCE M, et al. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia[J]. Neuron, 2021, S0896-6273(21)00194-X.
[17] WANG J, CHEN Z, WALSTON J D, et al. Alpha-Synuclein activates innate immunity but suppresses interferon-gamma expression in murine astrocytes[J]. Eur J Neurosci, 2018, 48(1): 1583-1599.
[18] OLANOW C W, SAVOLAINEN M, CHU Y, et al. Temporal evolution of microglia and α-synuclein accumulation following foetal grafting in Parkinson's disease[J]. Brain, 2019, 142(6): 1690-1700.
[19] RUAN C, SUN L, KROSHILINA A, et al. A novel Tmem119-tdTomato reporter mouse model for studying microglia in the central nervous system[J]. Brain Behav Immun, 2020, 83: 180-191.
[20] KAISER T, FENG G. Tmem119-EGFP and tmem119-CreERT2 transgenic mice for labeling and manipulating microglia[J]. eNeuro, 2019, 6(4): ENEURO.0448-18. 2019.
[21] ALE-AGHA N, GOY C, JAKOBS P, et al. CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system-New mode of action for caffeine[J]. PLoS Biol, 2018, 16(6): e2004408.
[22] SPYRIDOPOULOS I, FICHTLSCHERER S, POPP R, et al. Caffeine enhances endothelial repair by an AMPK-dependent mechanism[J]. Arterioscler Thromb Vasc Biol, 2008, 28(11): 1967-1974.