TY - JOUR
T1 - Developmental patterns in the regulation of chloride homeostasis and GABAA receptor signaling by seizures
AU - Galanopoulou, Aristea S.
PY - 2007/9
Y1 - 2007/9
N2 - GABAA receptors have dual functions during development. They depolarize immature neurons but hyperpolarize more mature neurons. This functional switch has been attributed to age-related differences in the relative abundance of cation chloride cotransporters, such as KCC2 and NKCC1, which regulate chloride homeostasis. Certain insults, such as trauma, ischemia, and seizures, if they occur when GABAAergic signaling is hyperpolarizing, such as in the adult brain, can lead to reappearance of the immature, depolarizing synaptic responses to GABAA receptor activation. In certain cases, this has been associated with either reduced expression of KCC2 or increase in NKCC1. In epilepsy, the depolarizing effects of GABAA receptors have been proposed to be important for the acquisition and/or maintenance of the epileptic state. Using the kainic acid model of status epilepticus, we have studied the effects of repetitive neonatal episodes of status epilepticus on the expression of cation chloride cotransporter KCC2 in the neonatal hippocampus. In contrast to adults, seizures increased KCC2 mRNA expression in the CA3 region of the neonatal hippocampus. The contrasting patterns of regulation of KCC2 by seizures in mature and immature neurons may be one of the age-related factors that protect the neonatal brain against the development of epilepsy.
AB - GABAA receptors have dual functions during development. They depolarize immature neurons but hyperpolarize more mature neurons. This functional switch has been attributed to age-related differences in the relative abundance of cation chloride cotransporters, such as KCC2 and NKCC1, which regulate chloride homeostasis. Certain insults, such as trauma, ischemia, and seizures, if they occur when GABAAergic signaling is hyperpolarizing, such as in the adult brain, can lead to reappearance of the immature, depolarizing synaptic responses to GABAA receptor activation. In certain cases, this has been associated with either reduced expression of KCC2 or increase in NKCC1. In epilepsy, the depolarizing effects of GABAA receptors have been proposed to be important for the acquisition and/or maintenance of the epileptic state. Using the kainic acid model of status epilepticus, we have studied the effects of repetitive neonatal episodes of status epilepticus on the expression of cation chloride cotransporter KCC2 in the neonatal hippocampus. In contrast to adults, seizures increased KCC2 mRNA expression in the CA3 region of the neonatal hippocampus. The contrasting patterns of regulation of KCC2 by seizures in mature and immature neurons may be one of the age-related factors that protect the neonatal brain against the development of epilepsy.
KW - Adult
KW - Chloride cotransporter
KW - Epilepsy
KW - GABA receptor
KW - Hippocampus
KW - KCC2
KW - Kainic acid
KW - NKCC1
KW - Neonatal
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=34848846555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34848846555&partnerID=8YFLogxK
U2 - 10.1111/j.1528-1167.2007.01284.x
DO - 10.1111/j.1528-1167.2007.01284.x
M3 - Article
C2 - 17910576
AN - SCOPUS:34848846555
SN - 0013-9580
VL - 48
SP - 14
EP - 18
JO - Epilepsia
JF - Epilepsia
IS - SUPPL. 5
ER -