Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes

Glutamine synthetase (GS) forms glutamine by catalyzing the ATP-dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer's disease and cell culture, GS has been detected in neurones. The present study demonstrates the expression of functional GS in cultured cerebellar granule cells and investigates conditions required to reduce this expression. Cerebellar granule cells from neonatal rats were grown in the absence of glutamine. Immunostaining revealed that the majority of neurones contained GS in their somata and dendrites. Treatment of neuronal cultures with glutamine greatly reduced the enzymatic activity of GS and also reduced the intensity of GS immunolabelling in dendrites. GS activity was reduced by 32% in neurones that had been transiently co-cultured with astrocytes, whereas GS immunoreactivity was largely abolished from neurones that had been directly seeded onto astrocytic monolayers. These results imply that GS expression in neurones occurs in response to a reduced availability of glutamine from astrocytes, and that neuronal GS expression represents a default phenotype which is normally suppressed via direct contacts with astrocytes. The aberrant expression of GS in sporadic neurones in Alzheimer's disease may indicate an impairment of such interactions.