The glutamine-glutamate cycle regulates synaptic glutamate release in the ventrolateral ventromedial nucleus of the hypothalamus of perinatal female rats

Journal of Neuroendocrinology
Shu-Ling Liang

Abstract

The astrocytic glutamine (Gln)-glutamate (Glu) cycle (GGC) supplies Gln for the regulation of glutamatergic synaptic transmission (GST) in the adult hippocampus. Increased synaptic Glu release in the perinatal ventrolateral ventromedial nucleus of the hypothalamus (vlVMH) modulates sexual differentiation, however, whether GGC regulates GST in the perinatal vlVMH has not been determined. Sex differences in oestradiol (E2 ) levels exist in the neonatal hypothalamus, and E2 increases levels of glutamine synthetase and glutaminase, two key enzymes involved in the GGC. Thus, it is hypothesised that sexually dimorphic phenotypes may exist in glutamatergic synapses associated with the GGC in the vlVMH in perinatal rats. Whole-cell voltage-clamp recordings in vlVMH neurones in brain slices from male and female pups revealed that pharmacological disruption of the GGC by α-(methylamino) isobutyric acid (5 mmol L-1 ), which blocks neuronal Gln uptake; or by l-methionine sulphoximine (1.5 mmol L-1 ), which inhibits astrocytic Gln synthesis, decreased miniature excitatory postsynaptic current (mEPSC) amplitudes in female but not male pups. By contrast, GGC interruptions decreased evoked (e)EPSC amplitudes in both sexes following increased s...Continue Reading

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