26. 07. 2024
Reading time: 5 minutes
An international team of scientists from the Italian National Research Council (CNR), the University of Bologna, and the Institute of Experimental Medicine of the CAS (Department of Cellular Neurophysiology) recently published their latest results in Nature Nanotechnology (open in a new window), which ranks among the most cited scientific journals, with an impact factor of 38.1. Using graphene electrodes, the researchers studied the possibility of stimulating calcium signalling in astrocytes, which may play a key role in the pathogenesis of a number of neurological diseases and the subsequent regeneration of nerve tissue.
Astrocytes are specialised glial cells that form a major part of the central nervous system (CNS). They are the most numerous and diverse cells in the brain and spinal cord and have a number of important features that significantly influence CNS functioning. Their main functions include metabolic and structural support of neurons and maintenance of the balance of ions and neurotransmitters in the extracellular space. In response to CNS injury, astrocytes become activated and, due to their ability to proliferate, form a barrier (glial scar) around the injured area, preventing further damage to the surrounding tissue. Concurrently, they contribute to the regeneration of nervous tissue by releasing a variety of anti-inflammatory cytokines and chemokines as part of the CNS immune response.
As aforementioned, astrocytes are multifunctional cells that are essential for maintaining normal CNS function and homeostasis, mainly through calcium signalling. This is why the international team of scientists has focused on understanding this essential mechanism by which glial cells communicate with neurons and other cells in the CNS. This signalling involves changes in intracellular calcium (Ca2+) concentration that can affect various cellular processes. The concentration of Ca2+ in astrocytes affects the release of specific substances such as glutamate, D-serine and ATP and modulates the activity of neighbouring astrocytes, neurons and vascular cells. Through these molecules, astrocytes regulate cerebral blood flow and can influence the balance between excitation and inhibition of brain activity. Disturbances in Ca2+ dynamics contribute to the development and progression of a wide range of neurological diseases, characterised mainly by cognitive impairment or changes in cerebral blood flow.
Current bioelectronic tools are primarily designed to study neurons, and are not suitable for controlling calcium signals in astrocytes. Therefore, the authors of this paper focused on the possibility of electrical stimulation of astrocytes in order to influence calcium signalling in these cells, and developed two types of electrodes that are coated with graphene oxide or its reduced variant. The results of the study showed that different conductive properties of the substrate affect the electric field at the cell-electrolyte or cell-material interface, leading to different signalling in both astrocyte cell culture and astrocytes in tissue sections of the mouse brain.
The authors of the study demonstrated that electrical stimulation of astrocytes with graphene oxide-coated electrodes induces a slow increase in intracellular calcium concentration, which is primarily mediated by calcium influx from the extracellular space, whereas reduced graphene oxide-coated electrodes induce a rapid increase in intracellular calcium concentration, solely due to Ca2+ release from intracellular stores. Using the patch-clamp technique, which allows the study of the electrical properties of cell membranes and ion channel behaviour at a very detailed level, including monitoring the effects of various pharmacological agents, and methods for imaging voltage changes and intracellular calcium concentrations using fluorescent dyes, they validated the results described above.
Nevertheless, calcium signalling in astrocytes remains a challenge for researchers to conduct further similar studies. However, the current research results have provided evidence of a simple tool for selectively controlling distinct calcium signals in brain astrocytes for use in neuroscience and experimental medicine. In the future, the newly proposed research model could target selectively novel neuromodulatory effects in pathological conditions such as ischemia, epilepsy and spreading depression, in which the diverse nature of astrocyte calcium signalling is implicated.