Distribution and possible roles of aquaporin 9 in the brain.

Aquaporin 9 (AQP9) is a member of the aquaporin channel family involved in water flux through plasma membranes and exhibits the distinct feature of being also permeable to monocarboxylates, such as lactate, and various solutes, including glycerol, carbamides, purines, pyrimidines, and urea. AQP9 is constitutively expressed at high levels in the liver. In the brain under physiological conditions, AQP9 was first observed in tanycytes, and then in astrocytes. Only recently, its expression was also shown in neurons. Neurons expressing AQP9 are catecholaminergic and glucose sensitive. The expression of neuronal AQP9 can be negatively regulated by insulin and in diabetic animals an increase in AQP9 expression is observed in the catecholaminergic nuclei of the hindbrain, similar to the regulation of AQP9 by insulin in the liver. Furthermore, after transient brain ischemia, AQP9 expression is increased in astrocytes and its regulation may implicate the MAP-kinase pathways stimulated in such pathological conditions. Despite these new data, the exact role of AQP9 in the brain is still unclear. However, we may hypothesize that AQP9 is implicated in brain energy metabolism, as a neutral solute channel. AQP9 could facilitate the diffusion of lactate from the astrocyte to the neuron. In glucose sensitive neurons, diffusion of lactate and glycerol could stimulate these neurons in a similar manner to glucose and could regulate the energy balance. In pathological conditions, induction of AQP9 in astrocytes could participate in the clearance of excess lactate in the extracellular space. These hypotheses concerning the function of brain AQP9 are still speculative and open new areas of investigation.