Differential effects of L- and D-lactate on memory encoding and consolidation: Potential role of HCAR1 signaling

Scavuzzo, Claire J.; Rakotovao, Irina; Dickson, Clayton T.

doi:10.1016/j.nlm.2019.107151

Cited by 31 publications

(26 citation statements)

References 37 publications

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“…Based on these metabolite data and other studies of the role of lactate in memory formation [23], we hypothesized that lactate could be a mediator of the improved memory response in our trials because lactate is commonly produced by all lactobacilli. Also, lactate was recently shown to be higher in brain samples from rats that consumed a dietary supplement containing Lactobacillus and Bifidobacterium strains, and the rats had an improved memory as a result [8].…”

Section: Resultsmentioning

confidence: 87%

Genetic and metabolic links between the murine microbiome and memory

et al. 2020

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Background: Recent evidence has linked the gut microbiome to host behavior via the gut-brain axis [1-3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free (GF) mice. Results: A genome-wide association analysis (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly associated with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a positive correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics analysis revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, we show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice. Conclusion: Together, this study provides new evidence for a link between Lactobacillus and memory and our results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites.

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Section: Resultsmentioning

confidence: 87%

Genetic and metabolic links between the murine microbiome and memory

et al. 2020

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“…Accordingly, hippocampal lactate increased (1.9 mM in the HIIT group vs. 1.4 mM in the Ctl group) immediately at the end of the exercise. Recently, the diverse roles of lactate in mediating brain function have been well characterized (Berthet et al, 2009;Lauritzen et al, 2014;Tang et al, 2014;Mosienko et al, 2015;Dienel, 2017;Magistretti and Allaman, 2018), such as mediating synaptic plasticity (Schurr et al, 1988;Yang et al, 2014;Margineanu et al, 2018;El Hayek et al, 2019;Scavuzzo et al, 2020), cerebral microvasculogenesis (Morland et al, 2017;Boitsova et al, 2018), and neuronal activity (Bozzo et al, 2013;Tang et al, 2014;Herrera-Lopez and Galvan, 2018;de Castro Abrantes et al, 2019). Therefore, we speculated that the lactate might be an intermediary between HIIT and increased hippocampal BDNF expression.…”

Section: Discussionmentioning

confidence: 96%

“…As a result, the level of brain lactate obviously increases (Rasmussen et al, 2011;Wiegers et al, 2017). The increased lactate can potentiate neuronal synaptic plasticity to promote learning and memory (Schurr et al, 1988;Yang et al, 2014;Margineanu et al, 2018;El Hayek et al, 2019;Scavuzzo et al, 2020), and control neuronal activity to mediate brain excitability (Bozzo et al, 2013;Tang et al, 2014;Herrera-Lopez and Galvan, 2018;de Castro Abrantes et al, 2019). In addition, lactate is likely to participate in the improvement and maintenance of brain mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Elevated Lactate by High-Intensity Interval Training Regulates the Hippocampal BDNF Expression and the Mitochondrial Quality Control System

Cai

Shang

et al. 2021

Front. Physiol.

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High-intensity interval training (HIIT) is reported to be beneficial to brain-derived neurotrophic factor (BDNF) biosynthesis. A key element in this may be the existence of lactate, the most obvious metabolic product of exercise. In vivo, this study investigated the effects of a 6-week HIIT on the peripheral and central lactate changes, mitochondrial quality control system, mitochondrial function and BDNF expression in mouse hippocampus. In vitro, primary cultured mice hippocampal cells were used to investigate the role and the underlying mechanisms of lactate in promoting mitochondrial function during HIIT. In vivo studies, we firstly reported that HIIT can potentiate mitochondrial function [boost some of the mitochondrial oxidative phosphorylation (OXPHOS) genes expression and ATP production], stimulate BDNF expression in mouse hippocampus along with regulating the mitochondrial quality control system in terms of promoting mitochondrial fusion and biogenesis, and suppressing mitochondrial fission. In parallel to this, the peripheral and central lactate levels elevated immediately after the training. In vitro study, our results revealed that lactate was in charge of regulating mitochondrial quality control system for mitochondrial function and thus may contribute to BDNF expression. In conclusion, our study provided the mitochondrial mechanisms of HIIT enhancing brain function, and that lactate itself can mediate the HIIT effect on mitochondrial quality control system in the hippocampus.

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“…Somewhat surprisingly, lactate was found to be higher in patients with mild AD than in patients with moderate-to-severe AD, although both groups showed lactate levels above what was detected in health age-matched controls [ 25 ]. In addition to being used as a metabolite, lactate can also affect brain function by activation of the hydroxycarboxylic acid receptor 1 (HCA 1 , also abbreviated as HCAR1 ( )) [ 26 , 27 , 28 , 29 , 30 ]. The lactate receptor HCA 1 is an inhibitory G-protein-coupled receptor (GPCR), and activation of the receptor leads to the inhibition of adenylyl cyclase.…”

Section: Introductionmentioning

confidence: 99%

The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle

Hadzic

Nguyen

Hosoyamada

et al. 2020

IJMS

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The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF. A lactate receptor, the hydroxycarboxylic acid receptor 1 (HCA1), is present in the brain, but whether it is located in the CP or in other periventricular structures has not been studied. Here, we investigated the distribution of HCA1 in the cerebral ventricular system using monomeric red fluorescent protein (mRFP)-HCA1 reporter mice. The reporter signal was only detected in the dorsal part of the third ventricle, where strong mRFP-HCA1 labeling was present in cells of the CP, the tela choroidea, and the neuroepithelial ventricular lining. Co-labeling experiments identified these cells as fibroblasts (in the CP, the tela choroidea, and the ventricle lining) and ependymal cells (in the tela choroidea and the ventricle lining). Our data suggest that the HCA1-containing fibroblasts and ependymal cells have the ability to respond to alterations in CSF lactate in body–brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer’s disease biomarker).

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Differential effects of L- and D-lactate on memory encoding and consolidation: Potential role of HCAR1 signaling

Cited by 31 publications

References 37 publications

Genetic and metabolic links between the murine microbiome and memory

Genetic and metabolic links between the murine microbiome and memory

Elevated Lactate by High-Intensity Interval Training Regulates the Hippocampal BDNF Expression and the Mitochondrial Quality Control System

The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle

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