Dissociated gender-specific effects of recurrent seizures on GABA signaling in CA1 pyramidal neurons:: Role of GABAA receptors

被引:121
作者
Galanopoulou, Aristea S. [1 ,2 ]
机构
[1] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA
关键词
seizure; patch clamp; GABA(A) receptor; development; hippocampus; histochemistry;
D O I
10.1523/JNEUROSCI.5180-07.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Early in development, the depolarizing GABA(A) ergic signaling is needed for normal neuronal differentiation. It is shown here that hyperpolarizing reversal potentials of GABA(A) ergic postsynaptic currents (E-GABA) appear earlier in female than in male rat CA1 pyramidal neurons because of increased potassium chloride cotransporter 2 (KCC2) expression and decreased bumetanide-sensitive chloride transport in females. Three episodes of neonatal kainic acid-induced status epilepticus (3KA-SE), each elicited at postnatal days 4 (P4)-P6, reverse the direction of GABA(A) ergic responses in both sexes. In males, 3KA-SE trigger a premature appearance of hyperpolarizing GABA(A) ergic signaling at P9, instead of P14. This is driven by an increase in KCC2 expression and decrease in bumetanide-sensitive chloride cotransport. In 3KA-SE females, E-GABA transiently becomes depolarizing at P8-P13 because of increase in the activity of a bumetanide-sensitive NKCC1 (sodium potassium chloride cotransporter 1)-like chloride cotransporter. However, females regain their hyperpolarizing GABA(A) ergic signaling at P14 and do not manifest spontaneous seizures in adulthood. In maternally separated stressed controls, a hyperpolarizing shift in EGABA was observed in both sexes, associated with decreased bumetanide-sensitive chloride cotransport, whereas KCC2 immunoreactivity was increased in males only. GABA(A) receptor blockade at the time of 3KA-SE or maternal separation reversed their effects on E-GABA. These data suggest that the direction of GABA(A)-receptor signaling may be a determining factor for the age and sex-specific effects of prolonged seizures in the hippocampus, because they relate to normal brain development and possibly epileptogenesis. These effects differ from the consequences of severe stress.
引用
收藏
页码:1557 / 1567
页数:11
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