The role of aquaporin-4 in synaptic plasticity, memory and disease

Since the discovery of aquaporins, it has become clear that the various mammalian aquaporins play critical physiological roles in water and ion balance in multiple tissues. Aquaporin-4 (AQP4), the principal aquaporin expressed in the central nervous system (CNS, brain and spinal cord), has been shown to mediate CNS water homeostasis. In this review, we summarize new and exciting studies indicating that AQP4 also plays critical and unanticipated roles in synaptic plasticity and memory formation. Next, we consider the role of AQP4 in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), neuromyelitis optica (NMO), epilepsy, traumatic brain injury (TBI), and stroke. Each of these conditions involves changes in AQP4 expression and/or distribution that may be functionally relevant to disease physiology. Insofar as AQP4 is exclusively expressed on astrocytes, these data provide new evidence of “astrocytopathy” in the etiology of diverse neurological diseases.