Cell specificity of altered cation–chloride cotransporter expression and GABAergic innervation in the epileptic cerebral cortex

Abstract

Evaluation of: Aronica E, Boer K, Redeker S et al.: Differential expression patterns of chloride transporters, Na⁺–K⁺–2Cl⁻cotransporter and K⁺–Cl⁻ cotransporter (KCC2), in epilepsy-associated malformations of cortical development. Neuroscience 145(1), 185–196 (2007). The study by Aronica and colleagues used immunocytochemistry to investigate the changes in the expression and distribution of cation–chloride cotransporters in the cerebral cortex of epileptic patients when compared with age-matched controls. The aim was to determine whether or not the deregulation of cation–chloride cotransporter expression might contribute to the hyperexcitability that leads to seizures. The authors studied brain tissue from patients with medically intractable epilepsy associated with different types of malformations, including focal cortical dysplasia type IIB, hemimegalencephaly and ganglioglioma. They found weak neuronal and glial expression of the Na⁺–K⁺–2 Cl⁻ cotransporter (NKCC1) in the normal control adult cortex, whereas NKCC1 was strongly expressed in different cell types from most patients, including large dysplastic neurons, balloon cells and astrocytes. In addition, the K⁺–Cl⁻ cotransporter (KCC2) was reported to be diffusely distributed in the neuropil of control tissue, although more intense somatic KCC2 immunostaining was associated with large dysplastic neurons but not balloon cells in epileptic patients. The intense expression of NKCC1 in dysplastic neurons and the altered subcellular distribution of KCC2 were compared with the situation in the immature normal cortex. The authors concluded that altered expression of cation–chloride cotransporters in epileptic patients, in conjunction with malformations in cortical development, may contribute to epileptogenicity.

Keywords: :

• cortical malformations
• epilepsy
• immunocytochemistry
• inhibition
• KCC2
• NKCC1
• western blot

Acknowledgements

This work was supported by the Ministerio de Educación y Cultura grants BFU2006–03855 to Alberto Muñoz and BFU2006–13395 to Javier de Felipe.