Effects of Mild Dehydration Stress on Spatial Learning and Brain Transcriptome Profiles in Aged Mice

Abstract

Severe dehydration has detrimental impact on various physiological functions in a whole lifespan. However, the effects of dehydration on brain functions in the elderly have not been fully elucidated yet. Therefore, we aimed to study the effects of mild dehydration on cognitive functions in the elderly using 2-year-old C57BL/6 mice. A limited access to water bottle of 15 min/day for 2 weeks sufficiently established dehydration mice model (DEH) and their physiological parameters and cognitive functions were compared with those of control mice with ad libitum water intake (CON). Dehydrated mice showed significantly higher level of plasma osmolality and vasopressin expression in the brain than control mice. FACS analysis of peripheral blood presented the percent of neutrophils was higher in DEH compared to CON. DEH had significantly higher concentration of serum corticosterone than CON. Depression statuses determined by TST were not different between DEH and CON groups. Next, their spatial learning and memory were measured by the Barnes maze test. Surprisingly, dehydrated mice showed better performance in spatial learning and spent less time to find the target during the test than control mice. To find the underlying mechanism, transcriptome of hippocampus were analyzed by RNA-sequencing. Transcripts related to functions of synaptic plasticity and long-term potentiation were dramatically activated in dehydrated mice compared to those of control. The immunostaining analysis of GFAP+ cells in DG and CA1 regions of hippocampus showed the numbers of astrocyte were greatly higher in DEH than CON. Taken together, although mild dehydration led to increase in the numbers of inflammatory cells in the blood, it promoted spatial learning and memory by modulating ADH-corticosterone axis and thereby enhancing synaptic plasticity. These results might provide new insights in the roles of mild physiological stress of dehydration played in cognitive functions in senescence.