Chloride transporters in physiological brain development and neurodevelopmental disorders: The case of the Down syndrome

Abstract Brain development is characterized by sequences of biological processes that lead to the formation of functional neural networks. All these processes are regulated by GABAergic transmission through Cl−-permeable GABAA receptors. In this context, the cation chloride cotransporters NKCC1 and KCC2 has gained a lot of attention in recent years. In this chapter, we describe how the finely tuned expression, localization and activity of the two transporters are highly implicated in neurodevelopmental processes. Moreover, we discuss how impairments of these cotransporters can affect the physiological brain development, leading to the onset of neurodevelopmental abnormalities that underlie several psychiatric/neurological conditions. Finally, we describe the recent finding on the involvement of altered NKCC1 expression in the cognitive deficits associated with Down syndrome, and a possible therapeutic strategy for DS as well as other neurodevelopmental disorders characterized by NKCC1/KCC2 abnormalities.