Aging is associated with gradual and variable changes of some cognitive functions in humans and animals but the causes of these changes and their individual variability remain unclear. Similarly, hydration is variable among individuals and the proportion of brain weight relative to total body weight decreases with age but it is not known how much of the change is due to water loses. In this study we quantify age–dependent changes in brain hydration and manipulate interstitial water chemical potential µw in hippocampal slices to explore possible causal connections.
Hydration, basal synaptic transmission, and LTP (late-phase long term potentiation, a model of synaptic plasticity) were studied in the brains of aging inbred mice. The hydration potential was determined from fluid transfer kinetics across brain explants submerged in baths of cerebrospinal fluid solutions of known colloidosmotic pressure. This potential equals the bath pressure at which there is no fluid transfer; that is when the µw in explant and bath are the same.
The hydration potential of brain tissue is surprisingly large and increases with age from 75 mmHg at 6 weeks to 106 mmHg at 40 weeks. This progressive dehydration is rapid during 1.5 to 10 months of age but appears to level off afterwards reaching approximately 15% loss of brain water. These same levels of dehydration were also achieved in juvenile mice after 12 hours of water deprivation. When dehydration was reproduced ex-vivo within these ranges in hippocampal slices of young mice <2 months-old, the basal synaptic responses in C1 pyramidal cells increased. Further, while the threshold for phosphorylation of the cAMP response-binding protein (a key step in the induction of gene expression in L-LTP) was reduced, the induction of L-LTP in tetanization protocols was inhibited.
These results indicate that compared to juvenile mice the brain of middle and old age mice is dehydrated and that dehydration induces changes in neuronal excitability and deregulates synaptic plasticity of C1 pyramidal cells in the hippocampus. Because hydration level plateaus at middle age, we speculate that mild dehydration in the mature brain could reflect selective adaptive responses in C1 hippocampal neurons to other age-dependent changes. For example, lower water activity -and the consequent increase in the activity of all solutes- could compensate for slower receptor turnover rates at synapses. This is consistent with the idea that physiologically, global optimization of brain function over the animal lifespan may come at the expense of adaptive changes in the efficiency of some cognitive processes; first to learn and follow later to teach and lead.
Audience Take away:
- Changes in water activity modulate neuronal function
- Water activity in brain tissue decreases with age
- water activity in the brain interstitium is lower than in cerebrospinal fluid