Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Daniel Lindberg, Ada Man Choi Ho, Lee Peyton, Doo Sup Choi

Research output: Contribution to journalArticle

Abstract

Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones. Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs. Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs. Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Lactic Acid
Brain
Homeostasis
Ethanol
Glucose
Injections
Astrocytes
Neurons
Data storage equipment
Long-Term Memory
Street Drugs
Metabolites
Ketones
Inbred C57BL Mouse
Energy Metabolism
Acetates

Keywords

  • Astrocyte
  • Energy Homeostasis
  • Glucose
  • Lactate
  • Monocarboxylate Transporter

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

@article{8573e9fea6104652a352cfb70d55408e,
title = "Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain",
abstract = "Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones. Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs. Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs. Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.",
keywords = "Astrocyte, Energy Homeostasis, Glucose, Lactate, Monocarboxylate Transporter",
author = "Daniel Lindberg and Ho, {Ada Man Choi} and Lee Peyton and Choi, {Doo Sup}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/acer.14137",
language = "English (US)",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

AU - Lindberg, Daniel

AU - Ho, Ada Man Choi

AU - Peyton, Lee

AU - Choi, Doo Sup

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones. Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs. Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs. Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

AB - Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones. Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs. Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs. Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

KW - Astrocyte

KW - Energy Homeostasis

KW - Glucose

KW - Lactate

KW - Monocarboxylate Transporter

UR - http://www.scopus.com/inward/record.url?scp=85069802017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069802017&partnerID=8YFLogxK

U2 - 10.1111/acer.14137

DO - 10.1111/acer.14137

M3 - Article

C2 - 31237693

AN - SCOPUS:85069802017

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

ER -