Sex differences in the effects of PARP inhibition on microglial phenotypes following neonatal stroke

Article Article scientifique Article Sex differences in the effects of PARP inhibition on microglial phenotypes following neonatal stroke eng 2018 author Charriaut-Marlangue Christiane author Leconte Claire author Csaba Zsolt author Chafa Linda author Pansiot Julien author Talatizi Mustapha author Simon Kristin author Moretti Raffaella author Marchand-Leroux Catherine author Baud Olivier 850348 author Besson Valérie 557509 10.1016/j.bbi.2018.05.022 29852289 1090-2139 Neonatal acute ischemic stroke is a cause of neonatal brain injury that occurs more frequently in males, resulting in associated neurobehavioral disorders. The bases for these sex differences are poorly understood but might include the number, morphology and activation of microglia in the developing brain when subjected to stroke. Interestingly, poly (ADP-ribose) polymerase (PARP) inhibition preferentially protects males against neonatal ischemia. This study aims to examine the effects of PJ34, a PARP inhibitor, on microglial phenotypes at 3 and 8 days and on neurobehavioral disorders in adulthood for both male and female P9 mice subjected to permanent middle cerebral artery occlusion (pMCAo). PJ34 significantly reduced the lesion size by 78% and reduced the density of CX3CR1gfp-labeled microglial cells by 46% when examined 3 days after pMCAo in male but not in female mice. Eight days after pMCAo, the number of Iba1+/Cox-2+ cells did not differ between male and female mice in the cortical peri-infarct region. In the amygdala, Iba1+/Cox-2+ (M1-like) cell numbers were significantly decreased in PJ34-treated males but not in females. Conversely, Iba1+/Arg-1+ (M2-like) and Arg-1+/Cox-2+ (Mtransitional) cell numbers were significantly increased in PJ34-treated females. Regarding neurobehavioral disorders during adulthood, pMCAo induced a motor coordination deficit and a spatial learning deficit in female mice only. PJ34 prevented MBP fibers, motor coordination and learning disorders during adulthood in female mice. Our data show significant sex differences in the effects of PARP inhibition on microglia phenotypes following neonatal ischemia, associated with improved behavior and myelination during adulthood in females only. Our findings suggest that modulating microglial phenotypes may play key roles in behavior disorders and white matter injury following neonatal stroke. Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false 1251 Prévention des complications néonatales d'origine périnatale 990 Brain, behavior, and immunity 0a4e8113-a5f4-446a-95fe-763edc906a2b Article (Published version) Restricted 1-s2.0-S0889159118301983-main.pdf 2870023 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Sex differences in the effects of PARP inhibition on microglial phenotypes following neonatal stroke	Brain, behavior, and immunity			2018	429	0

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Besson, Valérie