» Articles » PMID: 37960975

Astrocyte and L-lactate in the Anterior Cingulate Cortex Modulate Schema Memory and Neuronal Mitochondrial Biogenesis

Overview
Journal Elife
Specialty Biology
Date 2023 Nov 14
PMID 37960975
Authors
Affiliations
Soon will be listed here.
Abstract

Astrocyte-derived L-lactate was shown to confer beneficial effects on synaptic plasticity and cognitive functions. However, how astrocytic G signaling in the anterior cingulate cortex (ACC) modulates L-lactate levels and schema memory is not clear. Here, using chemogenetic approach and well-established behavioral paradigm, we demonstrate that astrocytic G pathway activation in the ACC causes significant impairments in flavor-place paired associates (PAs) learning, schema formation, and PA memory retrieval in rats. It also impairs new PA learning even if a prior associative schema exists. These impairments are mediated by decreased L-lactate in the ACC due to astrocytic G activation. Concurrent exogenous L-lactate administration bilaterally into the ACC rescues these impairments. Furthermore, we show that the impaired schema memory formation is associated with a decreased neuronal mitochondrial biogenesis caused by decreased L-lactate level in the ACC upon astrocytic G activation. Our study also reveals that L-lactate-mediated mitochondrial biogenesis is dependent on monocarboxylate transporter 2 (MCT2) and NMDA receptor activity - discovering a previously unrecognized signaling role of L-lactate. These findings expand our understanding of the role of astrocytes and L-lactate in the brain functions.

Citing Articles

Homeostasis to Allostasis: Prefrontal Astrocyte Roles in Cognitive Flexibility and Stress Biology.

Wulaer B, Holtz M, Nagai J Adv Neurobiol. 2024; 39:137-163.

PMID: 39190074 DOI: 10.1007/978-3-031-64839-7_6.


Astrocytic GPCR signaling in the anterior cingulate cortex modulates decision making in rats.

Akter M, Fu Z, Zheng X, Iqbal Z, Zhang N, Karim A Oxf Open Neurosci. 2024; 3:kvae010.

PMID: 38915791 PMC: 11194462. DOI: 10.1093/oons/kvae010.


Exercise-induced neuroplasticity: a new perspective on rehabilitation for chronic low back pain.

Zou J, Hao S Front Mol Neurosci. 2024; 17:1407445.

PMID: 38912176 PMC: 11191426. DOI: 10.3389/fnmol.2024.1407445.


Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood-Brain Barrier.

Schiera G, Di Liegro C, Schiro G, Sorbello G, Di Liegro I Cells. 2024; 13(2).

PMID: 38247841 PMC: 10813980. DOI: 10.3390/cells13020150.


Does astrocytic L-lactate enhance cognition through myelination?.

Akter M, Li Y Neural Regen Res. 2023; 19(6):1167-1168.

PMID: 37905847 PMC: 11467931. DOI: 10.4103/1673-5374.385872.

References
1.
Liu Y, Cheng A, Li Y, Yang Y, Kishimoto Y, Zhang S . SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nat Commun. 2019; 10(1):1886. PMC: 6478744. DOI: 10.1038/s41467-019-09897-1. View

2.
Rooney J, Ryde I, Sanders L, Howlett E, Colton M, Germ K . PCR based determination of mitochondrial DNA copy number in multiple species. Methods Mol Biol. 2014; 1241:23-38. PMC: 4312664. DOI: 10.1007/978-1-4939-1875-1_3. View

3.
Endo F, Kasai A, Soto J, Yu X, Qu Z, Hashimoto H . Molecular basis of astrocyte diversity and morphology across the CNS in health and disease. Science. 2022; 378(6619):eadc9020. PMC: 9873482. DOI: 10.1126/science.adc9020. View

4.
Urban D, Roth B . DREADDs (designer receptors exclusively activated by designer drugs): chemogenetic tools with therapeutic utility. Annu Rev Pharmacol Toxicol. 2014; 55:399-417. DOI: 10.1146/annurev-pharmtox-010814-124803. View

5.
Armbruster B, Li X, Pausch M, Herlitze S, Roth B . Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci U S A. 2007; 104(12):5163-8. PMC: 1829280. DOI: 10.1073/pnas.0700293104. View