Paris Postdocs Seminars – Ahlem Assali

Invité par l’Institut Jacques Monod, Ahlem Assali (Institut du cerveau, Paris) présentera un Paris Postdoc Seminar sur le thème :

Pregnancy induces cerebrovascular plasticity involved in the emergence of maternal behaviors

Résumé :

The adult cerebrovascular system is viewed as a very stable network, mainly required to provide nutrients and oxygen to the brain, and adapting to changes in neuronal activity via vasomotricity mechanisms (vasodilation and vasoconstriction). Using advanced 3D whole-brain immunolabeling/clearing protocols (iDisco+), light-sheet imaging, and computational tools (ClearMap), enabling accurate reconstruction of the brain vasculature, we were able to challenge this static conception of the cerebrovascular network in the context of neurophysiological adaptations occurring during and after pregnancy. Pregnant mice displayed an increase in vascular branch points in different brain regions compared to virgin females, starting at least at gestational day 6 (GD6), peaking around GD15, and reversed postweaning. This increased vascularization was notably found in the preoptic region of the hypothalamus, involved in pregnancy regulation and maternal behavior, and in cortical areas, such as the somatosensory cortex. GD15 females also displayed an increase in Erg+ endothelial cells in the same brain regions. In addition, GD6 and GD15 females showed an increase in the number of endothelial tip cells in the hypothalamic preoptic region. These data revealed a progressive vascular remodeling during pregnancy, associated to potential angiogenesis, in adulthood and healthy conditions. To identify molecular mechanisms driving this vascular plasticity, we explored the effects of steroid hormones on the vascular network. Interestingly, implants releasing estradiol induced an increase in the number of vascular branch points and of endothelial tip cells in the preoptic region of virgin females, recapitulating the changes found in pregnant females. These data suggest that estradiol hormones regulate, at least partially, the pregnancy-induced vascular plasticity. Importantly, using 3D whole-brain fluorescent in situ hybridization, we found an increase in Vegfa expression (vascular endothelial growth factor) in the hypothalamic preoptic region and somatosensory cortex. Vegfa downregulation by shRNA in the preoptic area blocked the pregnancy-induced vascular densification, and induced defects in maternal behavior post-birth using the pup retrieval assay.  Future transcriptomics experiments in the preoptic region will allow an agnostic search for further cellular and molecular mechanisms underlying pregnancy-induced vascular adaptations. Our data suggest an active role of vascular remodeling in shaping pregnancy- and maternal behaviors-related neuronal functions.