Neuron-glia interactions in the pathophysiology of epilepsy
Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of research into the role of glia in supporting and modulating neuronal activity, providing compelling evidence of glial involvement in the pathophysiology of epilepsy. The mechanisms by which glia, particularly astrocytes and microglia, may contribute to epilepsy and consequently could be harnessed therapeutically are discussed in this Review.
Scientists link concussions to seizures, development of epilepsy
Scientists from the Dr. Robel research team found that some astrocytes are altered in a new and unique way almost immediately after mild traumatic brain injury/concussion. Then, weeks later, the scientists observed spontaneous, recurrent seizures in those mice with most altered astrocytes.
AP-1 and the injury response of the GFAP gene
Increased GFAP gene expression is a common feature of CNS injury, resulting in its use as a reporter to investigate mechanisms producing gliosis. AP-1 transcription factors are among those proposed to participate in mediating the reactive response. Prior studies found a consensus AP-1 binding site in the GFAP promoter to be essential for activity of reporter constructs transfected into cultured cells, but to have little to no effect on basal transgene expression in mice. Since cultured astrocytes display some properties of reactive astrocytes, these findings suggested that AP-1 transcription factors are critical for the upregulation of GFAP in injury, but not for its resting level of expression.
Process- and bio-inspired hydrogels for 3D bioprinting of soft free-standing neural and glial tissues.
A bio-inspired hydrogel for 3D bioprinting of soft free-standing neural tissues is presented. The novel filler-free bioinks were designed by combining natural polymers for extracellular matrix biomimicry with synthetic polymers that endow desirable rheological properties for 3D bioprinting. Crosslinking of thiolated Pluronic F-127 with dopamine-conjugated (DC) gelatin and DC hyaluronic acid through a thiol - catechol reaction resulted in thermally gelling bioinks with Herschel-Bulkley fluid rheological behavior. Microextrusion 3D bioprinting was used to fabricate free-standing cell-laden tissue constructs.
Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus.
A subset of neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating depth and frequency of breathing in response to changes in tissue CO2/H+. The activity of chemosensitive RTN neurons is also subject to modulation by CO2/H+-dependent purinergic signaling. However, mechanisms contributing to purinergic regulation of RTN chemoreceptors are not entirely clear. Recent evidence suggests adenosine inhibits RTN chemoreception in vivo by activation of A1 receptors. The goal of this study was to characterize effects of adenosine on chemosensitive RTN neurons and identify intrinsic and synaptic mechanisms underlying this response.
Scientists solve century-old neuroscience mystery; answers may lead to epilepsy treatment
Scientists at the Virginia Tech Carilion Research Institute have solved a 125-year-old mystery of the brain, and, in the process, uncovered a potential treatment for acquired epilepsy. The School of Neuroscience is very proud to publish this great accomplishment of a research team led by our director, Harald Sontheimer. Scientists at the Virginia Tech Carilion Research Institute have solved a 125-year-old mystery of the brain, and, in the process, uncovered a potential treatment for acquired epilepsy.