A Tribute to Mary C. McKenna: Glutamate as Energy Substrate and Neurotransmitter-Functional Interaction Between Neurons and Astrocytes.

Glutamate metabolism in the brain is extremely complex not only involving a large variety of enzymes but also a tight partnership between neurons and astrocytes, the latter cells being in control of de novo synthesis of glutamate. This review provides an account of the processes involved, i.e. pyruvate carboxylation and recycling as well as the glutamate-glutamine cycle, focusing on the many seminal contributions from Dr. Mary McKenna. The ramification of the astrocytic end feet allowing contact and control of hundreds of thousands of synapses at the same time obviously puts these cells in a prominent position to regulate neural activity. Additionally, the astrocytes take active part in the neurotransmission processes by releasing a variety of gliotransmitters including glutamate. Hence, the term "the tripartite synapse", in which there is an active and dynamic interplay between the pre- and post-synaptic neurons and the ensheathing astrocytes, has been coined. The studies of Mary McKenna and her colleagues over several decades have been of paramount importance for the elucidation of compartmentation in astrocytes and synaptic terminals and the intricate metabolic processes underlying the glutamatergic neurotransmission process.