Targeting glycolysis for neuroprotection in early LPS-induced neuroinflammation

Adriana Fernanda K. Vizuete; Fernanda Fróes; Marina Seady; Aline Castro Caurio; Osmar Vieira Ramires Junior; Ana Karla Oliveira Leite; Clarissa Penha Farias; Angela T.S. Wyse; Carlos-Alberto Gonçalves

Brain, Behavior, & Immunity - Health (Dec 2024)

Targeting glycolysis for neuroprotection in early LPS-induced neuroinflammation

Adriana Fernanda K. Vizuete,
Fernanda Fróes,
Marina Seady,
Aline Castro Caurio,
Osmar Vieira Ramires Junior,
Ana Karla Oliveira Leite,
Clarissa Penha Farias,
Angela T.S. Wyse,
Carlos-Alberto Gonçalves

Affiliations

Adriana Fernanda K. Vizuete: Laboratory of Calcium-Binding Proteins in the CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil; Corresponding author. Department of Biochemistry, Instituto de Ciências Básicas da Saúde, UFRGS, Ramiro Barcelos, 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil.
Fernanda Fróes: Laboratory of Calcium-Binding Proteins in the CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil
Marina Seady: Laboratory of Calcium-Binding Proteins in the CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil
Aline Castro Caurio: Post Graduate Program in Biochemistry, Unipampa (Universidade Federal do Pampa) Campus Uruguaiana, Uruguaina, Rio Grande do Sul, Brazil
Osmar Vieira Ramires Junior: Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
Ana Karla Oliveira Leite: Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Translational Neuroscience (PGNET), National Institute of Translational Neuroscience, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
Clarissa Penha Farias: Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Translational Neuroscience (PGNET), National Institute of Translational Neuroscience, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
Angela T.S. Wyse: Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
Carlos-Alberto Gonçalves: Laboratory of Calcium-Binding Proteins in the CNS, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Post Graduate Program in Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil

Journal volume & issue: Vol. 42
p. 100901

Abstract

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Neuroinflammation is a pathophysiological feature of numerous neurological and psychiatric disorders. The immune response in the central nervous system, driven by microglia and astrocytes, leads to metabolic reprogramming towards aerobic glycolysis, a phenomenon known as the Warburg effect. The control of metabolic reprogramming via immunomodulation may represent a potential therapeutic target for providing protection against neuroinflammation, which contributes to neuronal dysfunction and death in several neurological disorders. For this purpose, we investigated putative neuroprotective effects of the downregulation of aerobic glycolysis using the 3PO inhibitor, and the downregulation of neuroinflammation using MCC950, in the early LPS-induced neuroinflammation model. The LPS-induced shift towards glycolysis, inflammatory and glial changes (IL-1β, NF-κB, COX2, Iba1, GFAP) were reversed by 3PO, which improved animal behavior. Additionally, MCC950 (an NLRP3 inhibitor) downregulated TLR4/Akt/p38 MAPK/NF-κB/STAT3 signaling, expressions of COX2 and IL-1β, and the astrocyte reactivity (decreasing GFAP) induced by early neuroinflammation, resulting in low glucose uptake. Our data support the occurrence of the Warburg effect during early neuroinflammation and suggest potential new approaches for the treatment of brain injury, given the role of neuroinflammation in such events.

Published in Brain, Behavior, & Immunity - Health

ISSN: 2666-3546 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-behavior-and-immunity-health

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