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

Brain, Behavior, and Immunity
Christiane Charriaut-MarlangueValérie C Besson

Abstract

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 significant...Continue Reading

Citations

Jul 25, 2019·Stroke; a Journal of Cerebral Circulation·Philippe BonninNathalie Kubis
Sep 24, 2019·Frontiers in Aging Neuroscience·Anne-Laure HemonnotHélène Hirbec
Aug 7, 2019·International Journal of Molecular Sciences·Sonia VillapolChristiane Charriaut-Marlangue
Feb 18, 2020·CNS Neuroscience & Therapeutics·Ling-Zhi LiYu-Min Luo
Sep 5, 2020·Nature Reviews. Drug Discovery·Nicola J Curtin, Csaba Szabo
Jan 9, 2021·Journal of Neuroscience Research·Rongjiao ShaoDerong Cui
Apr 4, 2021·International Journal of Molecular Sciences·Cody G YokubaitisSara Jane Ward
Jul 3, 2021·Current Issues in Molecular Biology·Philippe BonninChristiane Charriaut-Marlangue
Jul 10, 2021·Journal of Neurochemistry·Shuiqiao LiuYingfei Wang
Mar 2, 2019·Developmental Neuroscience·R Ann SheldonDonna M Ferriero

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