Sexually Dimorphic Effect of Glutamate Treatment on Cell Cycle Arrestment of Astrocytes from the Preoptic Area of Neonatal Rats

Neurotoxicological studies have indicated that L-glutamate exhibits more pronounced effects on the preoptic area (POA) neurons of male rats than on those of females in the neonatal period. However, no information has previously been available as to whether or not such sexual dimorphism also exists for the effects of glutamate on astrocytes from POA. The present paper reports the differential effects of L-glutamate on astrocytes isolated from POA of neonatal male and female rats. The proliferation of astrocytes was measured by methods of cell count and cell cycle analysis. In addition, the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) was assayed to understand its role in the glutamate-induced disturbance of the cell cycle progression of astrocytes. The results revealed that L-glutamate, at doses of 0.5 and 1.0 mM, inhibited the proliferation of astrocytes derived from male rats more severely than those derived from females. The L-glutamate treatment blocked the cell cycle progression and caused an accumulation of cells in the S phase. The activity of CaM kinase II declined more markedly in astrocytes derived from male rats than in those from females after glutamate treatment. These findings suggest that the proliferation of astrocytes derived from POA of neonatal rats can be inhibited in a sexually dimorphic manner by L-glutamate, possibly through blocking the cell cycle progression and partially related to the inactivation of the CaM kinase II.