Taste enhancer in the head? - Study on astroglial glutamine

Glutamate, the salt of glutamic acid, can be found in many different dishes and provides a hearty, spicy taste. Glutamine is also an amino acid that is released from astrocytes, non-neuronal cells in the brain, into the extracellular space and perceives important functions in the brain. A team of scientists around JARA-BRAIN member Prof. Joachim Lübke has now investigated the role of astroglial glutamine in synaptic activity.

In collaboration with the group of Prof. Nathalie Rouach, College de France Paris and the group of Prof. Joachim Lübke JARA-BRAIN Institute, Decoding the human brain at systemic levels INM-10, Research Centre Jülich it was possible to prove that glutamine, available through release from astrocytes, is required for synaptic activity and recognition memory.

Glutamate is the most frequently encountered excitatory neurotransmitter in the central nervous system. Accordingly, it is involved in various functions of our brain and is a basic necessity for the smooth operation of these functions. I However, excess of glutamate, acting as an excitatory neurotransmitter, in the brain over a longer period of time, led to excitotoxity, causally related to the death of neurons. The removal of glutamate is therefore an important process in the brain. Astrocytes, non-neuronal cells in the brain, convert glutamate into glutamine and in turn release the amino acid into the synaptic cleft.

In highly active processes such as epilepsy, this mechanism is thought to be due to the disruption of glutamate-glutamine homeostasis between neurons and astrocytes. In the present study, a fluorescent probe was generated that tracks glutamine in living astrocytes, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein involved in many biological processes such as muscle contraction or embryonic development, but most important in regulating synaptic activity. In addition, the protein is part of gap junction and hemichannel functions that enable intercellular communication (GJIC) between cells to regulate cell death, proliferation and differentiation.

The results of this study reveal an indispensable essential recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.

The original publication related to this study is available on the "nature communications" website: https://www.nature.com/articles/s41467-022-28331-7