ArticleFrontiers in molecular neuroscience2023
Exogenous L-lactate administration in rat hippocampus increases expression of key regulators of mitochondrial biogenesis and antioxidant defense.
Article in Frontiers in molecular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 31 citations in OpenAlex.
- PRKCD Orchestrates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats by Regulating PINK1/PRKN Mitophagy Pathway.Journal of cellular and molecular medicine · 2026Article
- HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intercellular Mitochondrial Transfer as Endogenous Neuroprotection: Mechanisms and Therapeutic Implications in Ischemic Stroke.Translational stroke research · 2026Review
- Lactate restores PGC1α and BDNF expression rescuing cognitive impairments in a mouse model for schizophrenia.Behavioural brain research · 2026Article
- The impact of exercise on brain mitochondrial health and its relevance to Alzheimer's disease.Brain and environment · 2026Article
- Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells.Frontiers in cell and developmental biology · 2026Article
- The lactate shuttle in ageing: a metabolic bridge between muscle fatigue and brain resilience.Frontiers in physiology · 2026Review
- Novel therapeutic strategies targeting mitochondrial quality control for metabolic dysfunction-associated steatotic liver disease.Frontiers in physiology · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Modulating the Expression of Exercise-induced lncRNAs: Implications for Cardiovascular Disease Progression.Journal of cardiovascular translational research · 2025Review
- Neurobiology of mitochondrial dynamics in sleep.The Journal of physiology · 2025Review
- A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making.Molecular psychiatry · 2025Article
- Lactate-induced metabolic signaling is the potential mechanism for reshaping the brain function - role of physical exercise.Frontiers in endocrinology · 2025Review
- The Effects of Exercise on Hippocampus-Based Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Possible Involvement of Hippocampal Monocarboxylate Transporter 2.Advances in neurobiology · 2025Review
- Endoplasmic Reticulum Stress Delays Choroid Development in the HCAR1 Knockout Mouse.The American journal of pathology · 2024Article
- Insights into Adaption and Growth Evolution: Genome-Wide Copy Number Variation Analysis in Chinese Hainan Yellow Cattle Using Whole-Genome Re-Sequencing Data.International journal of molecular sciences · 2024Article
- Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner.iScience · 2024Article
- Article
- Astrocytic GPCR signaling in the anterior cingulate cortex modulates decision making in rats.Oxford open neuroscience · 2024Article
- High-intensity interval training reduces Tau and beta-amyloid accumulation by improving lactate-dependent mitophagy in rats with type 2 diabetes.Iranian journal of basic medical sciences · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L-lactate plays a critical role in learning and memory. Studies in rats showed that administration of exogenous L-lactate into the anterior cingulate cortex and hippocampus (HPC) improved decision-making and enhanced long-term memory formation, respectively. Although the molecular mechanisms by which L-lactate confers its beneficial effect are an active area of investigations, one recent study found that L-lactate supplementation results in a mild reactive oxygen species burst and induction of pro-survival pathways. To further investigate the molecular changes induced by L-lactate, we injected rats with either L-lactate or artificial CSF bilaterally into the dorsal HPC and collected the HPC after 60 minutes for mass spectrometry. We identified increased levels of several proteins that include SIRT3, KIF5B, OXR1, PYGM, and ATG7 in the HPC of the L-lactate treated rats. SIRT3 (Sirtuin 3) is a key regulator of mitochondrial functions and homeostasis and protects cells against oxidative stress. Further experiments identified increased expression of the key regulator of mitochondrial biogenesis (PGC-1α) and mitochondrial proteins (ATPB, Cyt-c) as well as increased mitochondrial DNA (mtDNA) copy number in the HPC of L-lactate treated rats. OXR1 (Oxidation resistance protein 1) is known to maintain mitochondrial stability. It mitigates the deleterious effects of oxidative damage in neurons by inducing a resistance response against oxidative stress. Together, our study suggests that L-lactate can induce expression of key regulators of mitochondrial biogenesis and antioxidant defense. These findings create new research avenues to explore their contribution to the L-lactate's beneficial effect in cognitive functions as these cellular responses might enable neurons to generate more ATP to meet energy demand of neuronal activity and synaptic plasticity as well as attenuate the associated oxidative stress.
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