Glial cells keep appearing everywhere I look. No, I have not been shrunken by some Rick Moranis-like character and made to wander around the body (a reference to “Honey, I shrunk the kids”)! But, I have been wandering around the pages of journals, ever-so-slowly trying to get a grasp of how the nervous and immune systems talk to each-other. What usually stands out? Any description of the local and distant effects (and their mechanisms) of illness and injury. So here is my shortest possible take on one interesting study from a group in Switzerland.
Step 1:
Glial cell (e.g. astrocyte): thought to affect the firing at synapses (neuromodulation).
Glutamate: Astrocytes produce glutamate and keep it contained in internal pockets. When required, these pockets slowly move like little amoebas towards the astrocytic membrane. There they join up, open up, and spit out their contents.
Neuromodulation: An astrocyte, adjacent to a nerve synapse, fires. The astrocyte spits out glutamate. This makes the neighbouring nerve fire across its synapse.
Cytokine TNF-α: we always carry it in small amounts but add an injury or disease and the amount increases.
Step 2:
According to this study, remove TNF-α and the astrocyte glutamate system breaks down. Basically, the pockets of glutamate still join with the membrane but the process slows down like a truck in peak-hour traffic.
Why does this stop the astrocytic-stimulation of firing at the adjacent synapse? Astrocytes are always capable of slowly removing glutamate that they have released. But normally so much glutamate is released that the astrocytic clean-up system is overwhelmed and the adjacent synapse is stimulated. However, since the absence of TNF-α slows the glutamatergic-release system, the astrocytes can now slurp up the little glutamate that has been spat out and the potentiation of nerve firing does not take place.
Furthermore, the effect of TNF-α on the glutamate-release system is dependent on the concentration of TNF-α. At constitutive concentrations, TNF-α allows the glutamate mechanism to work. But increase the concentration of TNF and the glutamate release is directly stimulated. In other words, at higher concentrations TNF-α directly causes the synapse to fire.
Why is this interesting? Firstly, this is one small example of how injury and infection can modulate synaptic efficiency and activity. Secondly, this is another reminder of the complexity behind the fine homeostatic balancing act in which our bodies engage constantly. Lastly, this work was done on cells from the dentate gyrus in the hippocampus. This region is thought to be related to memory, depression, and stress. And, after all, my personal interest is in discovering mechanisms that may eventually uncover a tiny piece of the puzzle to our understanding of how illness can lead to systemic effects and neuroplasticity.
Luke Parkitny
Luke Parkitny is a PhD student at Neuroscience Research Australia. He is researching some of the factors that play a role in the development of complex regional pain syndrome (CRPS). Luke joins the Body in Mind team with a background of clinical practice and research in Western Australia. He has rapidly cultivated an interest in all things pain and has very successfully exploited every opportunity to share this knowledge with other health professionals and lay-persons. Link to Luke’s published research and here he is in person talking about what he does.
Reference:
Santello M, Bezzi P, & Volterra A (2011). TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron, 69 (5), 988-1001 PMID: 21382557