CON 4W) mice. Kidneys in 4 week and 7 week old mice showed significantly distinctive functional gene networks. Gene sets related to cell cycle regulators, fetal kidney patterning molecules and immature glomerular barrier integrity were upregulated in infantile kidneys while heightened expressions of genes associated with ion transport and drug metabolism were observed in juvenile kidneys. Western blot analysis was con-ducted to validate the protein levels of representative molecules in morpholog-ical and functional maturation in the kidney. GPC3 that mediates ureteric bud branching in the metanephros was slightly higher in infantile kidneys at the protein level compared to the juvenile kidneys. CYP4A that is one of the most critical proteins in xenobiotics and lipid metabolism had increased protein lev-els in juvenile kidneys with normal renal development. Dehydration during infancy suppressed renal growth by interrupting the SHH signaling pathway, which targets cell cycle regulators. Importantly, disruption of the developmen-tal program ultimately led to long-term alterations in renal filtration functions by causing a decline in glomerular filtration barrier integrity. We also investi-gated whether dehydration affects cognitive function. Dehydration from infan-cy to juvenile resulted in impairment of learning ability. In the Barnes maze test, dehydrated mice (RES 4W) showed 4 times longer latency to find a target hole after 4 days of training compared to control mice (CON 4W). Brain weight was determined at the end of experiment and there was no significant difference between control and dehydrated mice. A series of neurotrophic factor was ex-amined for their expression and we found only BDNF expression was signifi-cantly lower in RES 4W than CON 4W. The transcript level of BDNF only in hippocampus of RES 4W was significantly different from CON 4W. Next-generation RNA sequencing analysis in the brain revealed that CREB and its downstream target genes related to memory consolidation were significantly dysregulated by dehydration. These results suggest that sufficient water intake is required for normal renal growth and learning development during infancy. This study provides a meaningful perspective of pediatric dehydration with a molecular and physiological explanation of why infants are more vulnerable to dehydration than adults. Furthermore, these findings suggest new insights into the systemic effects of dehydration on development and may provide possible markers for clinical application in pediatric dehydration.
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Transcriptome Profiling Analysis of Kidneys and Brain in Dehydrated Infant Mice
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