Seeing stars
Cells known as astrocytes could be considered stars of the brain’s cellular cosmos. These star-shaped bodies help maintain neuronal health by regulating nutrients and directing the chemical messages neurons use to communicate. But when stressed, astrocytes are less stellar in that role—yet they can signal the early progression of neurodegenerative diseases. Better understanding the cells’ connections to neurodegeneration could help scientists chart courses for new approaches to care, and even prevention.
In glaucoma
On the neurological bridge between the eye and the brain, glaucoma can take hold. That’s where scientists have noticed astrocyte reactivity and changes in shape that correlate with the disease’s progressive vision loss.
“We know that these changes in astrocyte morphology can be detected before any [observable] neurodegeneration sets in,” Susannah Waxman, a doctoral student in the Laboratory of Ocular Biomechanics at Pitt, explains in a recent UPMC blog. However, identifying the specific shapes, twists and bends correlating with disease outside of rodent models has been largely limited to examining astrocyte cytoskeletons—which Waxman describes as “a lot like imagining what dinosaurs looked like based on what paleontologists know of their bones.”
To push past this limitation—with direction from Ian Sigal, a PhD associate professor of ophthalmology and of bioengineering and principal investigator—Waxman and colleagues from Pitt and Harvard University are using high resolution images to build 3D models of astrocytes.
Their work reveals previously unseen structural details of astrocytes that illuminate their size, shape and complexity, as well as their spatial relationships with their neighbors.
In Alzheimer’s
Astrocytes are “a new frontier explored in Alzheimer’s disease,” says Tharick Pascoal, an MD, PhD associate professor of psychiatry and neurology.
In a study published in Nature Medicine, postdoctoral researcher Bruna Bellaver of Pascoal’s lab and collaborators demonstrated that biological signs of astrocyte reactivity can be used to identify, track and understand the progression of Alzheimer’s. Pascoal and fellow Pitt psychiatry faculty Victor Villemagne, an MD, and Thomas Karikari, a PhD, are also authors on the study.
When astrocytes become stressed and reactive (changing in shape, gene expression and function) amid preclinical pathological changes in the brain, they release high levels of a protein (glial fibrillary acidic protein or GFAP), which can be detected in blood. As their reactivity persists, they lose their ability to support neuronal health.
The study found that abnormal levels of GFAP in blood samples from people without cognitive impairments indicated the onset of astrocyte reactivity, which correlated with neuronal dysfunction in the brain over time. Those protein levels also rose alongside the accumulation of amyloid-beta and phosphorylated tau proteins—precursors to clinical symptoms in Alzheimer’s.
“Astrocytes might be like a maestro in an orchestra guiding the musicians that are amyloid, tau and all the other cells into the disease pathway or health pathway,” Bellaver explains.
Eye astrocyte image: Reprinted from Experimental Eye Research, Vol. 230, Individual astrocyte morphology in the collagenous lamina cribrosa revealed by multicolor DiOlistic labeling, S. Waxman et al., 2023., with permission from Elsevier.
Brain images: Nature Medicine.
