title: Systemic activation of Toll-like receptor 2 suppresses mitochondrial respiration and exacerbates hypoxic-ischemic injury in the developing brain.
abstract: Infection and inflammation are known risk factors for neonatal brain injury. Mycoplasma and Gram-positive bacteria, for which Toll-like receptor 2 (TLR2) plays a key role in recognition and inflammatory response, are among the most common pathogens in the perinatal period. Here, we report that systemic activation of TLR2 by Pam3CSK4 (P3C) increases neural tissue loss and demyelination induced by subsequent hypoxia-ischemia (HI) in neonatal mice. High-resolution respirometry of brain isolated mitochondria revealed that P3C suppresses ADP-induced oxidative phosphorylation, the main pathway of cellular energy production. The results suggest that infection and inflammation might contribute to HI-induced energy failure.
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Amin
authors.initials: A
authors.lastname: Mottahedin
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Svedin
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Syam
authors.initials: S
authors.lastname: Nair
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Mohn
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: 2 Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK.|3 Perinatal Center, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Ek
authors.affiliation: 1 Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D010100:Oxygen
keywords: Cerebral palsy; birth asphyxia; metabolism; perinatal brain injury