BDNF, Reduced leads to Down Regulation, K-Cl co-transporter 2 (KCC2)

BDNF is a potent regulator of KCC2 not only during the developmental phase but also in the adult stage but in a different way, showing the maturation-dependent action of BDNF on KCC2 regulation (Ferrini and Konick, 2013). BDNF in mature neurons causes down-regulation of KCC2 in mRNA and protein level (Rivera et al., 2002; 2004). Other studies also suggest that BDNF up-regulates KCC2 after neuronal injury (Boulenguez et al., 2010) and after seizures (Puskarjov et al., 2014) and the suggested plausible reason is that the repairing procedure of the neurons demands properties similar to those of the immature neurons. Up to date, the exact mechanistic pathways that are followed in the different abovementioned cases are not well characterized and understood. In the most recent study of Puskarjov et al., 2014, BDNF-/- mice were utilized to show that in the absence of BDNF the seizure-induced up regulation of KCC2 was eliminated, but interestingly no change in early (P5-6) or later (P13-14) postnatal KCC2 expression was observed compared to the wild type littermates. However, the functionality of the protein was not investigated nor the ability of the neurons to extrude Cl- in the absence of BDNF. Additionally, other studies have shown that the up-regulation of KCC2 via the transcriptional factor Egr4 is also regulated by a different neurotrophic factor, the neurturin (Ludwig et al., 2011b). These results reveal that the same transcriptional pathways are downstream from different neurotrophic factors and they might lead to the same outcome under different conditions. This suggestion should be further investigated, as this could explain the compensation mechanisms that are activated in the total absence of BDNF, and which might be different from those that are triggered by the decrease of BDNF levels.