TY - JOUR
T1 - KCC2 expression levels are reduced in post mortem brain tissue of Rett syndrome patients
AU - Hinz, Lisa
AU - Torrella Barrufet, Joan
AU - Heine, Vivi M.
PY - 2019/12/3
Y1 - 2019/12/3
N2 - Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene. Deficient K+-Cl - co-transporter 2 (KCC2) expression is suggested to play a key role in the neurodevelopmental delay in RTT patients' neuronal networks. KCC2 is a major player in neuronal maturation by supporting the GABAergic switch, through the regulation of neuronal chlorine homeostasis. Previous studies suggest that MeCP2 mutations lead to changed KCC2 expression levels, thereby causing a disturbance in excitation/inhibition (E/I) balance. To investigate this, we performed protein and RNA expression analysis on post mortem brain tissue from RTT patients and healthy controls. We showed that KCC2 expression, in particular the KCC2a isoform, is relatively decreased in RTT patients. The expression of Na+-K+-Cl- co-transporter 1 (NKCC1), responsible for the inward transport of chlorine, is not affected, leading to a reduced KCC2/NKCC1 ratio in RTT brains. Our report confirms KCC2 expression alterations in RTT patients in human brain tissue, which is in line with other studies, suggesting affected E/I balance could underlie neurodevelopmental defects in RTT patients.
AB - Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene. Deficient K+-Cl - co-transporter 2 (KCC2) expression is suggested to play a key role in the neurodevelopmental delay in RTT patients' neuronal networks. KCC2 is a major player in neuronal maturation by supporting the GABAergic switch, through the regulation of neuronal chlorine homeostasis. Previous studies suggest that MeCP2 mutations lead to changed KCC2 expression levels, thereby causing a disturbance in excitation/inhibition (E/I) balance. To investigate this, we performed protein and RNA expression analysis on post mortem brain tissue from RTT patients and healthy controls. We showed that KCC2 expression, in particular the KCC2a isoform, is relatively decreased in RTT patients. The expression of Na+-K+-Cl- co-transporter 1 (NKCC1), responsible for the inward transport of chlorine, is not affected, leading to a reduced KCC2/NKCC1 ratio in RTT brains. Our report confirms KCC2 expression alterations in RTT patients in human brain tissue, which is in line with other studies, suggesting affected E/I balance could underlie neurodevelopmental defects in RTT patients.
KW - E/I imbalance
KW - KCC2-deficiency
KW - Neuronal network immaturity
KW - Rett syndrome
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UR - https://www.ncbi.nlm.nih.gov/pubmed/31796123
U2 - https://doi.org/10.1186/s40478-019-0852-x
DO - https://doi.org/10.1186/s40478-019-0852-x
M3 - Article
C2 - 31796123
SN - 2051-5960
VL - 7
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 196
ER -