Research into neuroglia—and astrocytes, in particular—has only recently come under the scientific spotlight. Our aim is to reveal the role of astrocytes in brain functionality in order to determine the cause of all forms of intractable cerebropathia.
Astrocytes are an integral part of the brain and are the major cell type in the brain. But despite their number and importance, their known biological contributions have been limited to mere supportive functions for neighboring neurons.
However, in recent years, the role of astrocytes has been re-evaluated, and numerous recent reports indicate that these cells have an important impact on many physiological and pathological phenomena. We are particularly interested in their ability to release various transmitters (termed “gliotransmitters”), including glutamate, d-serine, ATP, GABA, and taurine. It seems that astrocytes actively release various transmitters and communicate dynamically with neighboring neurons.
In addition, astrocytes wrap around each and every synapse and form a specialized structure called a “microdomain.” These microdomains meet the structural requirements for close communication between astrocytes and neurons.
In the course of investigating potential molecular mechanisms for the astrocytic release of gliotransmitters, we found that Ca2+ signaling and Ca2+ dependent channels(Ca2+ activated anion channels, in particular) are a critical component of the release machinery.
This is quite contrary to the well-known neuronal release mechanism that utilizes vesicular exocytosis machinery. We have obtained compelling evidence that astrocytes utilizes various ion channels—specifically, Ca2+ activated anion channels encoded by the bestrophin 1 gene—for the release of various gliotransmitters such as GABA and glutamate.
Thus, in addition to studying glia-neuron interactions via gliotransmitters, we also actively investigate the release mechanisms involving anion channels by direct permeation through the channel pore. Finally, we are also interested in the question of how G protein-coupled receptors interact with and modulate ion channels. Astrocytes are loaded with various GPCRs that cause Ca2+ increases as well as changes in cAMP levels. The signaling that cascades downstream from GPCRs dynamically controls ion channel functions. The pathological consequences of abnormal GPCR and Ca2+ signaling are evident in the case of glioblastoma cells that originate in normal astrocytes. In these cells, increased expression of GPCR and Ca2+ release channels contribute to the invasiveness and migratory behavior of these
cells, as well as the pathogenesis of glioblastoma.
- Glia-neuron interaction via gliotransmitters
– Role of gliotransmitters in synaptic transmission and plasticity
– Mechanism for the astrocytic release of gliotransmitters: glutamate, ATP, GABA, d-serine, taurine
- Anion channel function in glial cells and neurons:
– Brain distribution of mBest1
– Glutamate release by permeation through anion channels
– Tonic GABA release by anion channels
– Bestrophin channel mediation of AHP currents in neurons
– Volume regulation by anion channels
– Developmental role of bestrophin channel in Drosophila
- Ca2+ signaling in glial cells through GPCR and Ca2+ dependent channels
– Pathological role of Ca2+ signaling and receptor/channels in glioblastoma
- Interaction between GPCR and Ca2+ permeable channels.
– TRPV1 activation by DAG produced by GPCR
– Role of histamine receptors and the modulation of L-type Ca2+ channels in SCN neurons and circadian clocks
– GABAA receptor in the modulation of L-type Ca2+ channels in SCN neurons and circadian clocks