C-C chemokine receptor type 2 (CCR2) signaling protects neonatal male mice with hypoxic-ischemic hippocampal damage from developing spatial learning deficits.
Chemokines are a family of cytokines involved in the chemotaxis of leukocytes and other target cells by binding to specific G-protein-coupled receptors on their membranes. As such, the activation of C-C chemokine receptor type 2 (CCR2) is involved in the mobilization of "inflammatory" monocytes from bone marrow and in their recruitment to the brain under inflammatory/pathological conditions. In this study, we investigated whether CCR2 signaling could affect the progression of learning deficits and hippocampal damage in a model of neonatal hypoxic-ischemic (HI) brain injury. Postnatal day 3 wild-type (WT) and CCR2 knockout (KO) mice of both sexes were subjected to the Rice-Vannucci model of neonatal hypoxia-ischemia and were followed for up to 14 weeks. HI CCR2 KO male mice were the only animals to exhibit long-term spatial learning deficits in the T-water maze task, compared to their corresponding sham-operated controls. CCR2 KO mouse pups of both sexes had a lower number of circulating monocytes, although only HI CCR2 KO male mice exhibited reduced numbers of activated macrophages/microglia in the damaged hippocampus, compared to WT mice. However, no differences were observed in hippocampal atrophy between HI CCR2 KO and HI WT mice. These results suggest that CCR2 signaling can protect neonatal mice from developing spatial learning deficits after a HI insult, in a sex-specific fashion.
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier boul., Québec, Canada G1V 4G2. Electronic address: pedrompc@biof.ufrj.br.
Pedro M
PM
Pimentel-Coelho
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier boul., Québec, Canada G1V 4G2. Electronic address: Jean-Philippe.Michaud@crchul.ulaval.ca.
Jean-Philippe
JP
Michaud
Neuroscience Laboratory, CHU de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier boul., Québec, Canada G1V 4G2. Electronic address: Serge.Rivest@crchul.ulaval.ca.
Serge
S
Rivest
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007859:Learning Disabilities / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009000:Monocytes / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2
Chemokine; C–C chemokine receptor type 2 (CCR2); Monocyte; Neonatal encephalopathy; Neonatal hypoxia–ischemia; Neuroinflammation