Growing appreciation for astrocytes as active participants in nervous system development, neurovascular metabolic coupling, and neurological disease progression has stimulated recent investigation into specific astrocyte-secreted proteins that may mediate these functions. The current work utilized SILAC-generated isotope reference proteomes to quantify relative protein abundances between the astrocyte proteome and secretome. Multidimensional GeLC-MS/MS analysis of astrocyte conditioned media and cell lysates resulted in the relative quantification of 516 proteins, 92 of which were greater than 1.5-fold enriched in astrocyte-conditioned media (ACM). Eighty of the ACM-enriched proteins had N-terminal signal peptides, comprising well known classically secreted proteins, such as apolipoprotein E and SPARC, and several cathepsins that localize to endosomal/lysosomal compartments. The remaining twelve ACM-enriched proteins, such as vimentin, ferritins, and histones, lacked N-terminal signal peptides. Also, 47 proteins contained predicted N-terminal signal peptides but were not enriched in ACM (< 1.5-fold), 25 of which were localized to ER, Golgi, or mitochondria membrane-bound compartments. Overall, by combining quantitative proteomics with subcellular localization prediction, an informative description of protein distribution can be obtained, providing insights into protein secretion.

Accelerated maturation of brain parenchyma close to term‐equivalent age leads to rapid changes in diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age‐related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality—including 162 who had DTI scans. We analyzed the age‐related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age‐specific normative values of ADC (ages 34–46 weeks), and FA/MD (35–41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.

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