Acute systemic inflammation induces central mitochondrial damage and mnesic deficit in adult Swiss mice.
The aim of this study was to investigate how the brain is affected during systemic inflammation. For this purpose, Swiss mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 250microg/mouse) to mimic aspects of systemic infection. Spatial learning in Y-maze test demonstrated a differential learning profile during the training test between control and LPS-treated mice, with an alteration in the latter group. We show that systemic LPS-induced inflammation and oxidative injury as assessed by reactive oxygen species (ROS) and nitrites/nitrates (NOx) production associated with reduced glutathione (GSH) depletion, cyclooxygenase-2 (COX-2) expression, and lipid peroxidation. LPS also induced a loss in mitochondrial integrity as shown by a significant decrease in membrane potential and impairment in mitochondrial redox activity. Thus, peripheral inflammation by producing brain inflammation and oxidative injury causes mnesic deficits. It remains to determine whether such events can induce neuronal dysfunction/degeneration and, with time, lead to cholinergic deficiency, amyloid deposits and cognitive impairments as they occur in Alzheimer's disease.
Noble
Florence
F
Université Paris Descartes, UFR Pharmacie 4, avenue de l'Observatoire, F-75006 Paris, France.
Rubira
Elisabeth
E
Boulanouar
Mohamed
M
Palmier
Bruno
B
Plotkine
Michel
M
Warnet
Jean-Michel
JM
Marchand-Leroux
Catherine
C
Massicot
France
F
D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000209:etiology*; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D005978:Glutathione; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D028361:Mitochondrial Diseases / Q000209:etiology*; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000150:complications*
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; D005978:Glutathione