Sex influences gliovascular unit assembly and function in the developing mouse brain

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Abstract The gliovascular unit (GVU), a specialized interface between the brain and the vascular system, assembles and matures after birth and establishes essential homeostatic functions, including blood–brain barrier integrity, metabolic exchanges, fluid drainage, neurovascular coupling, and immune surveillance. Here, we systematically compared the postnatal maturation of the cortical GVU in male vs. female mice. On P15, males exhibited a transiently greater vessel density and a higher level of aquaporin 4 expression in perivascular astrocyte processes. Females exhibited a higher density of perivascular macrophages expressing the lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1), along with earlier development of arterial vascular smooth muscle cells and greater cerebral blood flow. Transcriptomic profiling during the P5–P120 period revealed sex-specific developmental trajectories within the GVU, with the most prominent differences on P5. Taken as a whole, our results highlight pronounced sex-dependent differences in GVU assembly, GVU maturation, and the development of molecular programs that might influence brain physiology and vulnerability to neurodevelopmental disorders.

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