Abstract
Studies of the last two decades have demonstrated the presence in astrocytic cell membranes of N-methyl-d-aspartate (NMDA) receptors (NMDARs), albeit their apparently low abundance makes demonstration of their presence and function more difficult than of other glutamate (Glu) receptor classes residing in astrocytes. Activation of astrocytic NMDARs directly in brain slices and in acutely isolated or cultured astrocytes evokes intracellular calcium increase, by mutually unexclusive ionotropic and metabotropic mechanisms. However, other than one report on the contribution of astrocyte-located NMDARs to astrocyte-dependent modulation of presynaptic strength in the hippocampus, there is no sound evidence for the significant role of astrocytic NMDARs in astrocytic-neuronal interaction in neurotransmission, as yet. Durable exposure of astrocytic and neuronal co-cultures to NMDA has been reported to upregulate astrocytic synthesis of glutathione, and in this way to increase the antioxidative capacity of neurons. On the other hand, overexposure to NMDA decreases, by an as yet unknown mechanism, the ability of cultured astrocytes to express glutamine synthetase (GS), aquaporin-4 (AQP4), and the inward rectifying potassium channel Kir4.1, the three astroglia-specific proteins critical for homeostatic function of astrocytes. The beneficial or detrimental effects of astrocytic NMDAR stimulation revealed in the in vitro studies remain to be proven in the in vivo setting.
Highlights
Research of the last few decades has promoted astrocytes from cells providing physical and metabolic support to neurons to being their indispensable partner in neurotransmission
Glu receptors present on astrocytes include metabotropic glutamate receptors and the three classes of ionotropic receptors: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR), kainic acid (KA) receptors (KAR), and N-methyl-D-aspartate receptors (NMDARs) [3,4,5]
NMDA-mediated responses to Glu were first successfully recorded in astrocytes in brain slices and in astrocytes derived from the brain by the fluorescence-activated cell sorting (FACS) technique [14], albeit interference of the direct response of astrocytes to NMDA by an indirect effect mediated by Glu transfer between astrocytes and neurons could not be excluded in this study
Summary
Research of the last few decades has promoted astrocytes from cells providing physical and metabolic support to neurons to being their indispensable partner in neurotransmission (for exhaustive reviews see [1,2]). One of the crucial tools which astrocytes use to communicate with neurons and to modulate their function are neurotransmitter receptors located on astrocytic cell membranes. Pioneering studies of the 1980s, which analysed electrophysiological and calcium flux-generating responses of astrocytes to Glu in primary cell culture preparations, failed to demonstrate the presence of functional NMDARs on astrocytes. The advent of experiments on acutely isolated brain slices led first to detailed characterisation of astrocytic AMPAR [11], the responses of which to Glu differed between astrocytes (i) in brain slices and in culture [12], and (ii) recorded in two different loci of the same brain region (hippocampus) [13]. Intensive work has led to the revival of cultured astrocytes as a valuable tool with which to study intracellular effects of stimulation of astrocytic NMDARs, including modulation of the responses by pathogenic events. Inconsistencies of the results obtained using different ex vivo and in vitro experimental settings and inherent limitations of the methodology used so far will be emphasised
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call