Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.

Published: Thursday 12th December 2024
ADVANCED SEARCH
Log in
Top

Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms

or
Journals by subject

Unlock free access to practice-relevant journal articles

Join our community of medical professionals and register now to access a handpicked selection of journal articles from Springer's Medical portfolio. 

Register today!

Editor's Choice | Journals

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Most read journal articles

Do statins affect cognitive health?

Healthy blood, healthy brain

Differentiating prodromal dementia: DLB vs AD

Collagen in the central nervous system: contributions to neurodegeneration and promise as a therapeutic target

Latest Journal Issues

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Looking for something specific?

Find articles from over 500 clinical journals from Springer with the search function.

Latest issues in Internal Medicine

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Cardiology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Diabetes & Endocrinology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Neurology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Oncology

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Pediatrics

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

Latest issues in Respiratory Medicine

scroll for more

use your arrow keys for more

scroll or use arrow keys for more

About journals on Springer Medicine

The range of medical journals on Springer Medicine is extremely diverse. It includes the current editions and archives of around 500 English-language journals from almost all medical disciplines published by Springer. 

The specialist literature is usually available both online in full text and as a PDF for download. The online view is optimized in such a way that the specialist texts can be read comfortably on all screen sizes, from desktops to tablets to smartphones. We also include features to support your use of the journals for your research, such as bookmark setting.

Whether you’re interested in internal medicine, surgery, general medicine, gynecology, orthopedics, neurology, or pediatrics, there are excellent journals in almost every subject area, such as the BMC Series, Diabetologia, Breast Cancer Research, Current Obesity Reports, CNS Drugs and many others, all of which are an integral part of the everyday life of doctors across Europe. 

The breadth of content from this suite of journals allows the Springer Medicine team to collect and deliver broad-ranging content across the full spectrum of medical knowledge, with a special focus on topics highlighted by these leading journals and their editorial boards and specialist authors. This guarantees a high quality of content and ensures that our readers are offered the most relevant topics in their respective specialist area. 

Our experienced clinical content managers constantly monitor the needs of medical professionals to provide up-to-date reports from international congresses, expert interviews, and a range of digestible content on emerging topics in the field of medicine.
Journal of Neuroinflammation
Published in:

Open Access 01-12-2024 | Alzheimer's Disease | Review

Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms

Authors: Yao Wang, Ping Li, Yuan Xu, Linyu Feng, Yongkang Fang, Guini Song, Li Xu, Zhou Zhu, Wei Wang, Qi Mei, Minjie Xie

Published in: Journal of Neuroinflammation | Issue 1/2024

Login to get access

Abstract

Brain takes up approximately 20% of the total body oxygen and glucose consumption due to its relatively high energy demand. Glucose is one of the major sources to generate ATP, the process of which can be realized via glycolysis, oxidative phosphorylation, pentose phosphate pathways and others. Lactate serves as a hub molecule amid these metabolic pathways, as it may function as product of glycolysis, substrate of a variety of enzymes and signal molecule. Thus, the roles of lactate in central nervous system (CNS) diseases need to be comprehensively elucidated. Histone lactylation is a novel lactate-dependent epigenetic modification that plays an important role in immune regulation and maintaining homeostasis. However, there’s still a lack of studies unveiling the functions of histone lactylation in the CNS. In this review, we first comprehensively reviewed the roles lactate plays in the CNS under both physiological and pathological conditions. Subsequently, we’ve further discussed the functions of histone lactylation in various neurological diseases. Furthermore, future perspectives regarding histone lactylation and its therapeutic potentials in stroke are also elucidated, which may possess potential clinical applications.
Literature
1.
Bonvento G, Bolanos JP. Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab. 2021;33:1546–64.PubMedCrossRef
2.
Jha MK, Morrison BM. Glia-neuron energy metabolism in health and diseases: new insights into the role of nervous system metabolic transporters. Exp Neurol. 2018;309:23–31.PubMedPubMedCentralCrossRef
3.
Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19:609–33.PubMedPubMedCentralCrossRef
4.
Magistretti PJ, Allaman I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat Rev Neurosci. 2018;19:235–49.PubMedCrossRef
5.
Bordone MP, Salman MM, Titus HE, Amini E, Andersen JV, Chakraborti B, Diuba AV, Dubouskaya TG, Ehrke E, de Espindola A, et al. The energetic brain - A review from students to students. J Neurochem. 2019;151:139–65.PubMedCrossRef
6.
7.
8.
Dienel GA. Brain glucose metabolism: integration of energetics with function. Physiol Rev. 2019;99:949–1045.PubMedCrossRef
9.
Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27:441–64.PubMedCrossRef
10.
Magistretti PJ, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron. 2015;86:883–901.PubMedCrossRef
11.
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574:575–80.PubMedPubMedCentralCrossRef
12.
13.
Chen AN, Luo Y, Yang YH, Fu JT, Geng XM, Shi JP, Yang J. Lactylation, a Novel Metabolic Reprogramming Code: current status and prospects. Front Immunol. 2021;12:688910.PubMedPubMedCentralCrossRef
14.
Perez-Escuredo J, Van Hee VF, Sboarina M, Falces J, Payen VL, Pellerin L, Sonveaux P. Monocarboxylate transporters in the brain and in cancer. Biochim Biophys Acta. 2016;1863:2481–97.PubMedPubMedCentralCrossRef
15.
Halestrap AP. The SLC16 gene family - structure, role and regulation in health and disease. Mol Aspects Med. 2013;34:337–49.PubMedCrossRef
16.
17.
Song W, Li D, Tao L, Luo Q, Chen L. Solute carrier transporters: the metabolic gatekeepers of immune cells. Acta Pharm Sin B. 2020;10:61–78.PubMedCrossRef
18.
Yamagata K. Lactate supply from astrocytes to neurons and its role in ischemic stroke-induced neurodegeneration. Neuroscience. 2022;481:219–31.PubMedCrossRef
19.
Miranda-Gonçalves V, Granja S, Martinho O, Honavar M, Pojo M, Costa BM, Pires MM, Pinheiro C, Cordeiro M, Bebiano G, et al. Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas. Oncotarget. 2016;7:46335–53.PubMedPubMedCentralCrossRef
20.
Li M, Sun P, Tu B, Deng G, Li D, He W. Hypoxia conduces the glioma progression by inducing M2 macrophage polarization via elevating TNFSF9 level in a histone-lactylation-dependent manner. Am J Physiol Cell Physiol. 2024;327:C487–504.PubMedCrossRef
21.
Bola BM, Chadwick AL, Michopoulos F, Blount KG, Telfer BA, Williams KJ, Smith PD, Critchlow SE, Stratford IJ. Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol Cancer Ther. 2014;13:2805–16.PubMedPubMedCentralCrossRef
22.
Lopez E, Karattil R, Nannini F, Weng-Kit Cheung G, Denzler L, Galvez-Cancino F, Quezada S, Pule MA. Inhibition of lactate transport by MCT-1 blockade improves chimeric antigen receptor T-cell therapy against B-cell malignancies. J Immunother Cancer 2023, 11.
23.
Blaszczak W, Williams H, Swietach P. Autoregulation of H(+)/lactate efflux prevents monocarboxylate transport (MCT) inhibitors from reducing glycolytic lactic acid production. Br J Cancer. 2022;127:1365–77.PubMedPubMedCentralCrossRef
24.
25.
Hashimoto T, Hussien R, Oommen S, Gohil K, Brooks GA. Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. Faseb j. 2007;21:2602–12.PubMedCrossRef
26.
Sangsuwan R, Thuamsang B, Pacifici N, Allen R, Han H, Miakicheva S, Lewis JS. Lactate exposure promotes immunosuppressive phenotypes in Innate Immune cells. Cell Mol Bioeng. 2020;13:541–57.PubMedPubMedCentralCrossRef
27.
Cai M, Wang H, Song H, Yang R, Wang L, Xue X, Sun W, Hu J. Lactate is answerable for brain function and treating Brain diseases: Energy Substrates and Signal Molecule. Front Nutr. 2022;9:800901.PubMedPubMedCentralCrossRef
28.
29.
30.
Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34:11929–47.PubMedPubMedCentralCrossRef
31.
Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, et al. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci. 2007;27:12255–66.PubMedPubMedCentralCrossRef
32.
Halim ND, McFate T, Mohyeldin A, Okagaki P, Korotchkina LG, Patel MS, Jeoung NH, Harris RA, Schell MJ, Verma A. Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons. Glia. 2010;58:1168–76.PubMedPubMedCentralCrossRef
33.
Bolaños JP, Almeida A, Moncada S. Glycolysis: a bioenergetic or a survival pathway? Trends Biochem Sci. 2010;35:145–9.PubMedCrossRef
34.
Lopez-Fabuel I, Le Douce J, Logan A, James AM, Bonvento G, Murphy MP, Almeida A, Bolaños JP. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc Natl Acad Sci U S A. 2016;113:13063–8.PubMedPubMedCentralCrossRef
35.
Proia P, Di Liegro CM, Schiera G, Fricano A, Di Liegro I. Lactate as a metabolite and a Regulator in the Central Nervous System. Int J Mol Sci 2016, 17.
36.
Beard E, Lengacher S, Dias S, Magistretti PJ, Finsterwald C. Astrocytes as key regulators of Brain Energy Metabolism: New Therapeutic perspectives. Front Physiol. 2021;12:825816.PubMedCrossRef
37.
Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A. 1994;91:10625–9.PubMedPubMedCentralCrossRef
38.
Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ. Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci. 1998;20:291–9.PubMedCrossRef
39.
Annoni F, Peluso L, Gouvea Bogossian E, Creteur J, Zanier ER, Taccone FS. Brain Protection after Anoxic Brain Injury. Is Lactate Supplementation Helpful? Cells; 2021. p. 10.
40.
Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang PW, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487:443–8.PubMedPubMedCentralCrossRef
41.
Nijland PG, Michailidou I, Witte ME, Mizee MR, van der Pol SM, van Het Hof B, Reijerkerk A, Pellerin L, van der Valk P, de Vries HE, van Horssen J. Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions. Glia. 2014;62:1125–41.PubMedCrossRef
42.
43.
Barros LF, Weber B. CrossTalk proposal: an important astrocyte-to-neuron lactate shuttle couples neuronal activity to glucose utilisation in the brain. J Physiol. 2018;596:347–50.PubMedPubMedCentralCrossRef
44.
Chuquet J, Quilichini P, Nimchinsky EA, Buzsáki G. Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex. J Neurosci. 2010;30:15298–303.PubMedPubMedCentralCrossRef
45.
46.
Volkenhoff A, Weiler A, Letzel M, Stehling M, Klämbt C, Schirmeier S. Glial glycolysis is essential for neuronal survival in Drosophila. Cell Metab. 2015;22:437–47.PubMedCrossRef
47.
Mächler P, Wyss MT, Elsayed M, Stobart J, Gutierrez R, von Faber-Castell A, Kaelin V, Zuend M, San Martín A, Romero-Gómez I, et al. In vivo evidence for a Lactate gradient from astrocytes to neurons. Cell Metab. 2016;23:94–102.PubMedCrossRef
48.
Sada N, Lee S, Katsu T, Otsuki T, Inoue T. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science. 2015;347:1362–7.PubMedCrossRef
49.
Dienel GA. Lack of appropriate stoichiometry: strong evidence against an energetically important astrocyte-neuron lactate shuttle in brain. J Neurosci Res. 2017;95:2103–25.PubMedCrossRef
50.
Dienel GA. Fueling and imaging brain activation. ASN Neuro 2012, 4.
51.
Díaz-García CM, Mongeon R, Lahmann C, Koveal D, Zucker H, Yellen G. Neuronal stimulation triggers neuronal glycolysis and not Lactate Uptake. Cell Metab. 2017;26:361–e374364.PubMedPubMedCentralCrossRef
52.
Yang S, Qin C, Hu ZW, Zhou LQ, Yu HH, Chen M, Bosco DB, Wang W, Wu LJ, Tian DS. Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system. Neurobiol Dis. 2021;152:105290.PubMedCrossRef
53.
Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, Bosco DB, Wu LJ, Tian DS. Dual functions of Microglia in ischemic stroke. Neurosci Bull. 2019;35:921–33.PubMedPubMedCentralCrossRef
54.
Bernier LP, York EM, MacVicar BA. Immunometabolism in the brain: how metabolism shapes microglial function. Trends Neurosci. 2020;43:854–69.PubMedCrossRef
55.
Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, et al. Single-cell RNA sequencing of Microglia throughout the mouse lifespan and in the injured brain reveals Complex Cell-State changes. Immunity. 2019;50:253–e271256.PubMedCrossRef
56.
Lynch MA. Can the emerging field of immunometabolism provide insights into neuroinflammation? Prog Neurobiol. 2020;184:101719.PubMedCrossRef
57.
Voloboueva LA, Emery JF, Sun X, Giffard RG. Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin. FEBS Lett. 2013;587:756–62.PubMedPubMedCentralCrossRef
58.
Gimeno-Bayón J, López-López A, Rodríguez MJ, Mahy N. Glucose pathways adaptation supports acquisition of activated microglia phenotype. J Neurosci Res. 2014;92:723–31.PubMedCrossRef
59.
Holland R, McIntosh AL, Finucane OM, Mela V, Rubio-Araiz A, Timmons G, McCarthy SA, Gun’ko YK, Lynch MA. Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice. Brain Behav Immun. 2018;68:183–96.PubMedCrossRef
60.
Nair S, Sobotka KS, Joshi P, Gressens P, Fleiss B, Thornton C, Mallard C, Hagberg H. Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo. Glia. 2019;67:1047–61.PubMedCrossRef
61.
62.
Monsorno K, Buckinx A, Paolicelli RC. Microglial metabolic flexibility: emerging roles for lactate. Trends Endocrinol Metab. 2022;33:186–95.PubMedCrossRef
63.
Amaral AI, Tavares JM, Sonnewald U, Kotter MR. Oligodendrocytes: development, physiology and glucose metabolism. Adv Neurobiol. 2016;13:275–94.PubMedCrossRef
64.
Rinholm JE, Hamilton NB, Kessaris N, Richardson WD, Bergersen LH, Attwell D. Regulation of oligodendrocyte development and myelination by glucose and lactate. J Neurosci. 2011;31:538–48.PubMedPubMedCentralCrossRef
65.
Sánchez-Abarca LI, Tabernero A, Medina JM. Oligodendrocytes use lactate as a source of energy and as a precursor of lipids. Glia. 2001;36:321–9.PubMedCrossRef
66.
Fünfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Möbius W, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485:517–21.PubMedPubMedCentralCrossRef
67.
Saab AS, Tzvetavona ID, Trevisiol A, Baltan S, Dibaj P, Kusch K, Möbius W, Goetze B, Jahn HM, Huang W, et al. Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism. Neuron. 2016;91:119–32.PubMedPubMedCentralCrossRef
68.
Kambe Y. Recent behavioral findings of pathophysiological involvement of lactate in the central nervous system. Biochim Biophys Acta Gen Subj. 2022;1866:130137.PubMedCrossRef
69.
O’Dowd BS, Gibbs ME, Ng KT, Hertz E, Hertz L. Astrocytic glycogenolysis energizes memory processes in neonate chicks. Brain Res Dev Brain Res. 1994;78:137–41.PubMedCrossRef
70.
Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C. Astroglial metabolic networks sustain hippocampal synaptic transmission. Science. 2008;322:1551–5.PubMedCrossRef
71.
Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011;144:810–23.PubMedPubMedCentralCrossRef
72.
73.
Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ. Learning-Induced Gene expression in the Hippocampus reveals a role of Neuron -Astrocyte metabolic coupling in Long Term Memory. PLoS ONE. 2015;10:e0141568.PubMedPubMedCentralCrossRef
74.
Shima T, Matsui T, Jesmin S, Okamoto M, Soya M, Inoue K, Liu YF, Torres-Aleman I, McEwen BS, Soya H. Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes. Diabetologia. 2017;60:597–606.PubMedCrossRef
75.
Harris RA, Lone A, Lim H, Martinez F, Frame AK, Scholl TJ, Cumming RC. Aerobic Glycolysis Is Required for Spatial Memory Acquisition But Not Memory Retrieval in Mice. eNeuro 2019, 6.
76.
Boury-Jamot B, Carrard A, Martin JL, Halfon O, Magistretti PJ, Boutrel B. Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine. Mol Psychiatry. 2016;21:1070–6.PubMedCrossRef
77.
Zhang Y, Xue Y, Meng S, Luo Y, Liang J, Li J, Ai S, Sun C, Shen H, Zhu W, et al. Inhibition of Lactate Transport erases drug memory and prevents drug Relapse. Biol Psychiatry. 2016;79:928–39.PubMedCrossRef
78.
Lucas SJ, Michel CB, Marra V, Smalley JL, Hennig MH, Graham BP, Forsythe ID. Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse. J Physiol. 2018;596:1699–721.PubMedPubMedCentralCrossRef
79.
Margineanu MB, Mahmood H, Fiumelli H, Magistretti PJ. L-Lactate regulates the expression of synaptic plasticity and neuroprotection genes in cortical neurons: a transcriptome analysis. Front Mol Neurosci. 2018;11:375.PubMedPubMedCentralCrossRef
80.
Yang J, Ruchti E, Petit JM, Jourdain P, Grenningloh G, Allaman I, Magistretti PJ. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci U S A. 2014;111:12228–33.PubMedPubMedCentralCrossRef
81.
Goyal MS, Hawrylycz M, Miller JA, Snyder AZ, Raichle ME. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metab. 2014;19:49–57.PubMedPubMedCentralCrossRef
82.
Goyal MS, Vlassenko AG, Blazey TM, Su Y, Couture LE, Durbin TJ, Bateman RJ, Benzinger TL, Morris JC, Raichle ME. Loss of Brain Aerobic glycolysis in normal human aging. Cell Metab. 2017;26:353–e360353.PubMedPubMedCentralCrossRef
83.
El Hayek L, Khalifeh M, Zibara V, Abi Assaad R, Emmanuel N, Karnib N, El-Ghandour R, Nasrallah P, Bilen M, Ibrahim P, et al. Lactate mediates the effects of Exercise on Learning and Memory through SIRT1-Dependent activation of hippocampal brain-derived neurotrophic factor (BDNF). J Neurosci. 2019;39:2369–82.PubMedPubMedCentral
84.
Lambertus M, Øverberg LT, Andersson KA, Hjelden MS, Hadzic A, Haugen ØP, Storm-Mathisen J, Bergersen LH, Geiseler S, Morland C. L-lactate induces neurogenesis in the mouse ventricular-subventricular zone via the lactate receptor HCA(1). Acta Physiol (Oxf). 2021;231:e13587.PubMedCrossRef
85.
Lev-Vachnish Y, Cadury S, Rotter-Maskowitz A, Feldman N, Roichman A, Illouz T, Varvak A, Nicola R, Madar R, Okun E. L-Lactate promotes adult hippocampal neurogenesis. Front Neurosci. 2019;13:403.PubMedPubMedCentralCrossRef
86.
Nagase M, Takahashi Y, Watabe AM, Kubo Y, Kato F. On-site energy supply at synapses through monocarboxylate transporters maintains excitatory synaptic transmission. J Neurosci. 2014;34:2605–17.PubMedPubMedCentralCrossRef
87.
Parsons MP, Hirasawa M. ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal. J Neurosci. 2010;30:8061–70.PubMedPubMedCentralCrossRef
88.
Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, Teschemacher AG. Lactate-mediated glia-neuronal signalling in the mammalian brain. Nat Commun. 2014;5:3284.PubMedCrossRef
89.
90.
de Castro Abrantes H, Briquet M, Schmuziger C, Restivo L, Puyal J, Rosenberg N, Rocher AB, Offermanns S, Chatton JY. The lactate receptor HCAR1 modulates neuronal network activity through the activation of G(α) and G(βγ) subunits. J Neurosci. 2019;39:4422–33.PubMedPubMedCentralCrossRef
91.
Herrera-López G, Galván EJ. Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1. Hippocampus. 2018;28:557–67.PubMedCrossRef
92.
Dienel GA. Brain lactate metabolism: the discoveries and the controversies. J Cereb Blood Flow Metab. 2012;32:1107–38.PubMedCrossRef
93.
Vafaee MS, Vang K, Bergersen LH, Gjedde A. Oxygen consumption and blood flow coupling in human motor cortex during intense finger tapping: implication for a role of lactate. J Cereb Blood Flow Metab. 2012;32:1859–68.PubMedPubMedCentralCrossRef
94.
Alessandri B, Schwandt E, Kamada Y, Nagata M, Heimann A, Kempski O. The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats. J Neurotrauma. 2012;29:2181–91.PubMedCrossRef
95.
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest. 2013;123:1988–98.PubMedPubMedCentralCrossRef
96.
Lin AL, Fox PT, Hardies J, Duong TQ, Gao JH. Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex. Proc Natl Acad Sci U S A. 2010;107:8446–51.PubMedPubMedCentralCrossRef
97.
Hein TW, Xu W, Kuo L. Dilation of retinal arterioles in response to lactate: role of nitric oxide, guanylyl cyclase, and ATP-sensitive potassium channels. Invest Ophthalmol Vis Sci. 2006;47:693–9.PubMedCrossRef
98.
Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, MacVicar BA. Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature. 2008;456:745–9.PubMedPubMedCentralCrossRef
99.
van Meijel LA, van Asten JJA, Grandjean J, Heerschap A, Tack CJ, van der Graaf M, Wiegers EC, de Galan BE. Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes. BMJ Open Diabetes Res Care 2022, 10.
100.
Yamanishi S, Katsumura K, Kobayashi T, Puro DG. Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature. Am J Physiol Heart Circ Physiol. 2006;290:H925–934.PubMedCrossRef
101.
Bharadwaj S, Venkatraghavan L, Mariappan R, Ebinu J, Meng Y, Khan O, Tung T, Reyhani S, Bernstein M, Zadeh G. Serum lactate as a potential biomarker of non-glial brain tumors. J Clin Neurosci. 2015;22:1625–7.PubMedCrossRef
102.
Campbell BCV, De Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM, Donnan GA. Ischaemic stroke. Nat Rev Dis Primers. 2019;5:70.PubMedCrossRef
103.
Qin C, Yang S, Chu YH, Zhang H, Pang XW, Chen L, Zhou LQ, Chen M, Tian DS, Wang W. Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2022;7:215.PubMedPubMedCentralCrossRef
104.
Henriksen O, Gideon P, Sperling B, Olsen TS, Jørgensen HS, Arlien-Søborg P. Cerebral lactate production and blood flow in acute stroke. J Magn Reson Imaging. 1992;2:511–7.PubMedCrossRef
105.
Cvoro V, Wardlaw JM, Marshall I, Armitage PA, Rivers CS, Bastin ME, Carpenter TK, Wartolowska K, Farrall AJ, Dennis MS. Associations between diffusion and perfusion parameters, N-acetyl aspartate, and lactate in acute ischemic stroke. Stroke. 2009;40:767–72.PubMedCrossRef
106.
Berthet C, Lei H, Thevenet J, Gruetter R, Magistretti PJ, Hirt L. Neuroprotective role of lactate after cerebral ischemia. J Cereb Blood Flow Metab. 2009;29:1780–9.PubMedCrossRef
107.
Berthet C, Castillo X, Magistretti PJ, Hirt L. New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration. Cerebrovasc Dis. 2012;34:329–35.PubMedCrossRef
108.
Tseng MT, Chan SA, Schurr A. Ischemia-induced changes in monocarboxylate transporter 1 reactive cells in rat hippocampus. Neurol Res. 2003;25:83–6.PubMedCrossRef
109.
Zhang F, Vannucci SJ, Philp NJ, Simpson IA. Monocarboxylate transporter expression in the spontaneous hypertensive rat: effect of stroke. J Neurosci Res. 2005;79:139–45.PubMedCrossRef
110.
Moreira TJ, Pierre K, Maekawa F, Repond C, Cebere A, Liljequist S, Pellerin L. Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells. J Cereb Blood Flow Metab. 2009;29:1273–83.PubMedCrossRef
111.
Schurr A, Payne RS, Miller JJ, Tseng MT, Rigor BM. Blockade of lactate transport exacerbates delayed neuronal damage in a rat model of cerebral ischemia. Brain Res. 2001;895:268–72.PubMedCrossRef
112.
Yu X, Zhang R, Wei C, Gao Y, Yu Y, Wang L, Jiang J, Zhang X, Li J, Chen X. MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke. Anim Cells Syst (Seoul). 2021;25:93–101.PubMedCrossRef
113.
Schurr A. Lactate, glucose and energy metabolism in the ischemic brain (review). Int J Mol Med. 2002;10:131–6.PubMed
114.
Pu J, Han J, Yang J, Yu L, Wan H. Anaerobic Glycolysis and ischemic stroke: from mechanisms and Signaling pathways to Natural Product Therapy. ACS Chem Neurosci. 2024;15:3090–105.PubMedCrossRef
115.
Shen Z, Jiang L, Yuan Y, Deng T, Zheng YR, Zhao YY, Li WL, Wu JY, Gao JQ, Hu WW, et al. Inhibition of G protein-coupled receptor 81 (GPR81) protects against ischemic brain injury. CNS Neurosci Ther. 2015;21:271–9.PubMedCrossRef
116.
Jourdain P, Allaman I, Rothenfusser K, Fiumelli H, Marquet P, Magistretti PJ. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade. Sci Rep. 2016;6:21250.PubMedPubMedCentralCrossRef
117.
Castillo X, Rosafio K, Wyss MT, Drandarov K, Buck A, Pellerin L, Weber B, Hirt L. A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia. J Cereb Blood Flow Metab. 2015;35:1561–9.PubMedPubMedCentralCrossRef
118.
Valenzuela PL, Castillo-García A, Morales JS, de la Villa P, Hampel H, Emanuele E, Lista S, Lucia A. Exercise benefits on Alzheimer’s disease: state-of-the-science. Ageing Res Rev. 2020;62:101108.PubMedCrossRef
119.
Wang Q, Duan L, Li X, Wang Y, Guo W, Guan F, Ma S. Glucose Metabolism, Neural Cell Senescence and Alzheimer’s Disease. Int J Mol Sci 2022, 23.
120.
121.
Liguori C, Stefani A, Sancesario G, Sancesario GM, Marciani MG, Pierantozzi M. CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2015;86:655–9.PubMedCrossRef
122.
Liguori C, Chiaravalloti A, Sancesario G, Stefani A, Sancesario GM, Mercuri NB, Schillaci O, Pierantozzi M. Cerebrospinal fluid lactate levels and brain 18F FDG PET hypometabolism within the default mode network in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2016;43:2040–9.PubMedCrossRef
123.
Verri M, Aquilani R, Ricevuti G, Rondanelli M, Ghitti M, Bongiorno AI, Venturini L, Buonocore D, Boschi F, Dossena M. Plasma energy substrates at two stages of Alzheimer’s disease in humans. Int J ImmunoPathol Pharmacol 2018, 32.
124.
Zhang M, Cheng XF, Dang RZ, Zhang WW, Zhang J, Yao ZX. Lactate deficit in an Alzheimer Disease Mouse Model: the relationship with neuronal damage. J Neuropathol Exp Neurol. 2018;77:1163–76.PubMedCrossRef
125.
Zheng J, Xie Y, Ren L, Qi L, Wu L, Pan X, Zhou J, Chen Z, Liu L. GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer’s disease. Mol Metab. 2021;47:101180.PubMedPubMedCentralCrossRef
126.
Zebhauser PT, Berthele A, Goldhardt O, Diehl-Schmid J, Priller J, Ortner M, Grimmer T. Cerebrospinal fluid lactate levels along the Alzheimer’s disease continuum and associations with blood-brain barrier integrity, age, cognition, and biomarkers. Alzheimers Res Ther. 2022;14:61.PubMedPubMedCentralCrossRef
127.
Kavanagh K, Day SM, Pait MC, Mortiz WR, Newgard CB, Ilkayeva O, McClain DA, Macauley SL. Type-2-Diabetes alters CSF but not plasma metabolomic and AD risk profiles in Vervet monkeys. Front Neurosci. 2019;13:843.PubMedPubMedCentralCrossRef
128.
Redjems-Bennani N, Jeandel C, Lefebvre E, Blain H, Vidailhet M, Guéant JL. Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients. Gerontology. 1998;44:300–4.PubMedCrossRef
129.
Parnetti L, Reboldi GP, Gallai V. Cerebrospinal fluid pyruvate levels in Alzheimer’s disease and vascular dementia. Neurology. 2000;54:735–7.PubMedCrossRef
130.
Malm J, Kristensen B, Ekstedt J, Adolfsson R, Wester P. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters. J Neurol Neurosurg Psychiatry. 1991;54:252–9.PubMedPubMedCentralCrossRef
131.
Leen WG, Willemsen MA, Wevers RA, Verbeek MM. Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. PLoS ONE. 2012;7:e42745.PubMedPubMedCentralCrossRef
132.
Lu WT, Sun SQ, Li Y, Xu SY, Gan SW, Xu J, Qiu GP, Zhuo F, Huang SQ, Jiang XL, Huang J. Curcumin ameliorates memory deficits by enhancing Lactate Content and MCT2 expression in APP/PS1 transgenic mouse model of Alzheimer’s Disease. Anat Rec (Hoboken). 2019;302:332–8.PubMedCrossRef
133.
Hypoxia-sensing VGLL4 promotes LDHA-driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer’s disease. Faseb Journal 2023, 37.
134.
Ravera S, Torazza C, Bonifacino T, Provenzano F, Rebosio C, Milanese M, Usai C, Panfoli I, Bonanno G. Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1(G93A) mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS. J Neurochem. 2019;151:336–50.PubMedCrossRef
135.
Liu FT, Ge JJ, Wu JJ, Wu P, Ma Y, Zuo CT, Wang J. Clinical, dopaminergic, and metabolic correlations in Parkinson Disease: a dual-Tracer PET Study. Clin Nucl Med. 2018;43:562–71.PubMedCrossRef
136.
Schirinzi T, Di Lazzaro G, Sancesario GM, Summa S, Petrucci S, Colona VL, Bernardini S, Pierantozzi M, Stefani A, Mercuri NB, Pisani A. Young-onset and late-onset Parkinson’s disease exhibit a different profile of fluid biomarkers and clinical features. Neurobiol Aging. 2020;90:119–24.PubMedCrossRef
137.
Fedotova EI, Dolgacheva LP, Abramov AY, Berezhnov AV. Lactate and pyruvate activate autophagy and Mitophagy that protect cells in toxic model of Parkinson’s Disease. Mol Neurobiol. 2022;59:177–90.PubMedCrossRef
138.
Komilova NR, Angelova PR, Berezhnov AV, Stelmashchuk OA, Mirkhodjaev UZ, Houlden H, Gourine AV, Esteras N, Abramov AY. Metabolically induced intracellular pH changes activate mitophagy, autophagy, and cell protection in familial forms of Parkinson’s disease. FEBS J. 2022;289:699–711.PubMedCrossRef
139.
Li J, Chen L, Qin Q, Wang D, Zhao J, Gao H, Yuan X, Zhang J, Zou Y, Mao Z, et al. Upregulated hexokinase 2 expression induces the apoptosis of dopaminergic neurons by promoting lactate production in Parkinson’s disease. Neurobiol Dis. 2022;163:105605.PubMedCrossRef
140.
Xu Y, Liu C, Chen S, Ye Y, Guo M, Ren Q, Liu L, Zhang H, Xu C, Zhou Q, et al. Activation of AMPK and inactivation of akt result in suppression of mTOR-mediated S6K1 and 4E-BP1 pathways leading to neuronal cell death in in vitro models of Parkinson’s disease. Cell Signal. 2014;26:1680–9.PubMedPubMedCentralCrossRef
141.
Rahman MH, Bhusal A, Kim JH, Jha MK, Song GJ, Go Y, Jang IS, Lee IK, Suk K. Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes. Nat Commun. 2020;11:5906.PubMedPubMedCentralCrossRef
142.
Tsai SF, Chen YW, Kuo YM. High-fat diet reduces the hippocampal content level of lactate which is correlated with the expression of glial glutamate transporters. Neurosci Lett. 2018;662:142–6.PubMedCrossRef
143.
Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O’Connell MT, Czosnyka M, Smielewski P, Pickard JD, Menon DK, Kirkpatrick PJ, et al. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain. 2011;134:484–94.PubMedCrossRef
144.
Dienel GA. Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. J Cereb Blood Flow Metab. 2014;34:1736–48.PubMedPubMedCentralCrossRef
145.
Wettervik TS, Engquist H, Howells T, Rostami E, Hillered L, Enblad P, Lewén A. Arterial lactate in traumatic brain injury - relation to intracranial pressure dynamics, cerebral energy metabolism and clinical outcome. J Crit Care. 2020;60:218–25.CrossRef
146.
147.
Bajamal AH, Apriawan T, Ranuh I, Servadei F, Faris M, Al Fauzi A. Comparison of half-molar sodium lactate and mannitol to treat brain edema in severe traumatic brain injury: a systematic review. Chin J Traumatol. 2021;24:344–9.PubMedPubMedCentralCrossRef
148.
Holloway R, Zhou Z, Harvey HB, Levasseur JE, Rice AC, Sun D, Hamm RJ, Bullock MR. Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat. Acta Neurochir (Wien). 2007;149:919–27. discussion 927.PubMedCrossRef
149.
Ichai C, Payen JF, Orban JC, Quintard H, Roth H, Legrand R, Francony G, Leverve XM. Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial. Intensive Care Med. 2013;39:1413–22.PubMedCrossRef
150.
Chen T, Qian YZ, Rice A, Zhu JP, Di X, Bullock R. Brain lactate uptake increases at the site of impact after traumatic brain injury. Brain Res. 2000;861:281–7.PubMedCrossRef
151.
Glenn TC, Kelly DF, Boscardin WJ, McArthur DL, Vespa P, Oertel M, Hovda DA, Bergsneider M, Hillered L, Martin NA. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab. 2003;23:1239–50.PubMedCrossRef
152.
Zhai X, Li J, Li L, Sun Y, Zhang X, Xue Y, Lv J, Gao Y, Li S, Yan W, et al. L-lactate preconditioning promotes plasticity-related proteins expression and reduces neurological deficits by potentiating GPR81 signaling in rat traumatic brain injury model. Brain Res. 2020;1746:146945.PubMedCrossRef
153.
Millet A, Cuisinier A, Bouzat P, Batandier C, Lemasson B, Stupar V, Pernet-Gallay K, Crespy T, Barbier EL, Payen JF. Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury. Br J Anaesth. 2018;120:1295–303.PubMedCrossRef
154.
Baxter LR Jr., Schwartz JM, Phelps ME, Mazziotta JC, Guze BH, Selin CE, Gerner RH, Sumida RM. Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry. 1989;46:243–50.PubMedCrossRef
155.
Su L, Cai Y, Xu Y, Dutt A, Shi S, Bramon E. Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry. 2014;14:321.PubMedPubMedCentralCrossRef
156.
Kennedy SH, Evans KR, Krüger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ. Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry. 2001;158:899–905.PubMedCrossRef
157.
Pan SM, Zhou YF, Zuo N, Jiao RQ, Kong LD, Pan Y. Fluoxetine increases astrocytic glucose uptake and glycolysis in corticosterone-induced depression through restricting GR-TXNIP-GLUT1 pathway. Front Pharmacol. 2022;13:872375.PubMedPubMedCentralCrossRef
158.
Allaman I, Fiumelli H, Magistretti PJ, Martin JL. Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology. 2011;216:75–84.PubMedCrossRef
159.
Shaif NA, Chang DH, Cho D, Kim S, Seo DB, Shim I. The antidepressant-like Effect of Lactate in an animal model of Menopausal Depression. Biomedicines 2018, 6.
160.
Carrard A, Cassé F, Carron C, Burlet-Godinot S, Toni N, Magistretti PJ, Martin JL. Role of adult hippocampal neurogenesis in the antidepressant actions of lactate. Mol Psychiatry. 2021;26:6723–35.PubMedPubMedCentralCrossRef
161.
Karnib N, El-Ghandour R, El Hayek L, Nasrallah P, Khalifeh M, Barmo N, Jabre V, Ibrahim P, Bilen M, Stephan JS, et al. Lactate is an antidepressant that mediates resilience to stress by modulating the hippocampal levels and activity of histone deacetylases. Neuropsychopharmacology. 2019;44:1152–62.PubMedPubMedCentralCrossRef
162.
Liberti MV, Locasale JW. Histone lactylation: a New Role for glucose metabolism. Trends Biochem Sci. 2020;45:179–82.PubMedCrossRef
163.
Varner EL, Trefely S, Bartee D, von Krusenstiern E, Izzo L, Bekeova C, O’Connor RS, Seifert EL, Wellen KE, Meier JL, Snyder NW. Quantification of lactoyl-CoA (lactyl-CoA) by liquid chromatography mass spectrometry in mammalian cells and tissues. Open Biol. 2020;10:200187.PubMedPubMedCentralCrossRef
164.
Dai X, Lv X, Thompson EW, Ostrikov KK. Histone lactylation: epigenetic mark of glycolytic switch. Trends Genet. 2022;38:124–7.PubMedCrossRef
165.
166.
Moreno-Yruela C, Zhang D, Wei W, Bæk M, Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, et al. Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 2022;8:eabi6696.PubMedPubMedCentralCrossRef
167.
Jin J, Bai L, Wang D, Ding W, Cao Z, Yan P, Li Y, Xi L, Wang Y, Zheng X, et al. SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth. EMBO Rep. 2023;24:e56052.PubMedPubMedCentralCrossRef
168.
Dai SK, Liu PP, Li X, Jiao LF, Teng ZQ, Liu CM. Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development. Development 2022, 149.
169.
Gaffney DO, Jennings EQ, Anderson CC, Marentette JO, Shi T, Schou Oxvig AM, Streeter MD, Johannsen M, Spiegel DA, Chapman E, et al. Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell Chem Biol. 2020;27:206–e213206.PubMedCrossRef
170.
Chen L, Huang L, Gu Y, Cang W, Sun P, Xiang Y. Lactate-lactylation hands between metabolic reprogramming and immunosuppression. Int J Mol Sci 2022, 23.
171.
Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X, Jia R. Histone lactylation drives oncogenesis by facilitating m(6)a reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021;22:85.PubMedPubMedCentralCrossRef
172.
Wang N, Wang W, Wang X, Mang G, Chen J, Yan X, Tong Z, Yang Q, Wang M, Chen L, et al. Histone lactylation boosts reparative gene activation post-myocardial infarction. Circ Res. 2022;131:893–908.PubMedCrossRef
173.
Hu X, Huang J, Li Z, Li J, Ouyang F, Chen Z, Li Y, Zhao Y, Wang J, Yu S, et al. Lactate promotes microglial scar formation and facilitates locomotor function recovery by enhancing histone H4 lysine 12 lactylation after spinal cord injury. J Neuroinflammation. 2024;21:193.PubMedPubMedCentralCrossRef
174.
An YJ, Jo S, Kim JM, Kim HS, Kim HY, Jeon SM, Han D, Yook JI, Kang KW, Park S. Lactate as a major epigenetic carbon source for histone acetylation via nuclear LDH metabolism. Exp Mol Med. 2023;55:2238–47.PubMedPubMedCentralCrossRef
175.
Li H, Chawla G, Hurlburt AJ, Sterrett MC, Zaslaver O, Cox J, Karty JA, Rosebrock AP, Caudy AA, Tennessen JM. Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth. Proc Natl Acad Sci U S A. 2017;114:1353–8.PubMedPubMedCentralCrossRef
176.
Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, Liao Y, Yan Y, Li Q, Zhou X, et al. Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer’s disease. Cell Metab. 2022;34:634–e648636.PubMedCrossRef
177.
Yang W, Wang P, Cao P, Wang S, Yang Y, Su H, Nashun B. Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice. Epigenetics Chromatin. 2021;14:57.PubMedPubMedCentralCrossRef
178.
Tian Q, Zhou LQ. Lactate activates germline and cleavage embryo genes in mouse embryonic stem cells. Cells 2022, 11.
179.
Xiong J, He J, Zhu J, Pan J, Liao W, Ye H, Wang H, Song Y, Du Y, Cui B, et al. Lactylation-driven METTL3-mediated RNA m(6)a modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 2022;82:1660–e16771610.PubMedCrossRef
180.
Yang Q, Liu J, Wang Y, Zhao W, Wang W, Cui J, Yang J, Yue Y, Zhang S, Chu M, et al. A proteomic atlas of ligand-receptor interactions at the ovine maternal-fetal interface reveals the role of histone lactylation in uterine remodeling. J Biol Chem. 2022;298:101456.PubMedCrossRef
181.
Li L, Chen K, Wang T, Wu Y, Xing G, Chen M, Hao Z, Zhang C, Zhang J, Ma B, et al. Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade. Nat Metab. 2020;2:882–92.PubMedCrossRef
182.
Irizarry-Caro RA, McDaniel MM, Overcast GR, Jain VG, Troutman TD, Pasare C. TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation. Proc Natl Acad Sci U S A. 2020;117:30628–38.PubMedPubMedCentralCrossRef
183.
Chu X, Di C, Chang P, Li L, Feng Z, Xiao S, Yan X, Xu X, Li H, Qi R, et al. Lactylated histone H3K18 as a potential biomarker for the diagnosis and Predicting the severity of septic shock. Front Immunol. 2021;12:786666.PubMedCrossRef
184.
Wang L, Wang Y, Meng M, Ma N, Wei G, Huo R, Chang G, Shen X. High-concentrate diet elevates histone lactylation mediated by p300/CBP through the upregulation of lactic acid and induces an inflammatory response in mammary gland of dairy cows. Microb Pathog. 2023;180:106135.PubMedCrossRef
185.
Yao X, Li C. Lactate dehydrogenase A mediated histone lactylation induced the pyroptosis through targeting HMGB1. Metab Brain Dis. 2023;38:1543–53.PubMedCrossRef
186.
Zhou Y, Yang L, Liu X, Wang H. Lactylation may be a Novel Posttranslational modification in inflammation in neonatal hypoxic-ischemic Encephalopathy. Front Pharmacol. 2022;13:926802.PubMedPubMedCentralCrossRef
187.
Su J, Zheng Z, Bian C, Chang S, Bao J, Yu H, Xin Y, Jiang X. Functions and mechanisms of lactylation in carcinogenesis and immunosuppression. Front Immunol. 2023;14:1253064.PubMedPubMedCentralCrossRef
188.
Yang Z, Zheng Y, Gao Q. Lysine lactylation in the regulation of tumor biology. Trends Endocrinol Metab 2024.
189.
Zhang Y, Song H, Li M, Lu P. Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: oncometabolite fuels oncogenic transcription. Clin Transl Med. 2024;14:e1614.PubMedPubMedCentralCrossRef
190.
Wang Y, Wang W, Su L, Ji F, Zhang M, Xie Y, Zhang T, Jiao J. BACH1 changes microglial metabolism and affects astrogenesis during mouse brain development. Dev Cell. 2024;59:108–e124107.PubMedCrossRef
191.
Hagihara H, Shoji H, Otabi H, Toyoda A, Katoh K, Namihira M, Miyakawa T. Protein lactylation induced by neural excitation. Cell Rep. 2021;37:109820.PubMedCrossRef
192.
Lu J, Fu S, Dai J, Hu J, Li S, Ji H, Wang Z, Yu J, Bao J, Xu B, et al. Integrated metabolism and epigenetic modifications in the macrophages of mice in responses to cold stress. J Zhejiang Univ Sci B. 2022;23:461–80.PubMedPubMedCentralCrossRef
193.
Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10:217–24.PubMedCrossRef
194.
Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O’Loughlin E, Xu Y, Fanek Z, et al. The TREM2-APOE pathway drives the Transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017;47:566–e581569.PubMedPubMedCentralCrossRef
195.
Wei L, Yang X, Wang J, Wang Z, Wang Q, Ding Y, Yu A. H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer’s disease through the NFκB signaling pathway. J Neuroinflammation. 2023;20:208.PubMedPubMedCentralCrossRef
196.
Han H, Zhao Y, Du J, Wang S, Yang X, Li W, Song J, Zhang S, Zhang Z, Tan Y, et al. Exercise improves cognitive dysfunction and neuroinflammation in mice through histone H3 lactylation in microglia. Immun Ageing. 2023;20:63.PubMedPubMedCentralCrossRef
197.
Fatemi A, Wilson MA, Johnston MV. Hypoxic-ischemic encephalopathy in the term infant. Clin Perinatol 2009, 36:835–858, vii.
198.
199.
Zhang F, Zhou J, Lu P, Zhang X, Yang L, Wu J, Zhang L, Zhang L, Pang J, Xie H, et al. Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage. J Neuroinflammation. 2024;21:186.PubMedPubMedCentralCrossRef
200.
Brouns R, Sheorajpanday R, Wauters A, De Surgeloose D, Mariën P, De Deyn PP. Evaluation of lactate as a marker of metabolic stress and cause of secondary damage in acute ischemic stroke or TIA. Clin Chim Acta. 2008;397:27–31.PubMedCrossRef
201.
Banerjee A, Ghatak S, Sikdar SK. l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro. J Neurochem. 2016;138:265–81.PubMedCrossRef
202.
Kalinichenko SG, Matveeva NY, Korobtsov AV. Brain-derived neurotrophic factor (BDNF) as a Regulator of apoptosis under conditions of focal experimental stroke. Bull Exp Biol Med. 2020;169:701–6.PubMedCrossRef
203.
Hertz L, Peng L, Dienel GA. Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab. 2007;27:219–49.PubMedCrossRef
204.
Semenza GL. Hypoxia-inducible factor 1: Control of Oxygen Homeostasis in Health and Disease. Pediatr Res. 2001;49:614–7.PubMedCrossRef
205.
Ullah MS, Davies AJ, Halestrap AP. The plasma membrane Lactate Transporter MCT4, but not MCT1, is Up-regulated by Hypoxia through a HIF-1α-dependent Mechanism*. J Biol Chem. 2006;281:9030–7.PubMedCrossRef
206.
Wu A, Lee D, Xiong WC. Lactate Metabolism, Signaling, and function in Brain Development, synaptic plasticity, angiogenesis, and neurodegenerative diseases. Int J Mol Sci 2023, 24.
Metadata
Title
Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms
Authors
Yao Wang
Ping Li
Yuan Xu
Linyu Feng
Yongkang Fang
Guini Song
Li Xu
Zhou Zhu
Wei Wang
Qi Mei
Minjie Xie
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-024-03303-4

Other articles of this Issue 1/2024

Metformin attenuates central sensitization by regulating neuroinflammation through the TREM2-SYK signaling pathway in a mouse model of chronic migraine

Ependymal cells: roles in central nervous system infections and therapeutic application

AIBP controls TLR4 inflammarafts and mitochondrial dysfunction in a mouse model of Alzheimer’s disease

Impact of perinatal factors on T cells and transcriptomic changes in preterm infant brain injury

  • Open Access
  • Original Research

IKKβ deletion from CNS macrophages increases neuronal excitability and accelerates the onset of EAE, while from peripheral macrophages reduces disease severity

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

Image Credits