Tiny Crystals May Help Scientists Trace Causes of Brain Inflammation in Parkinson’s, Study Reports

Tiny and traceable man-made crystals, known as quantum dots, may be useful in carrying toxins to select cells in the brain, allowing researchers to better understand Parkinson’s neurodegenerative processes by being able to model and visualize them, researchers in Canada report.

Their study, “Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration,” was published in NeuroToxicology.

Microglia, primary immune cells of the brain and spinal cord, are known to contribute to the inflammation that underlies Parkinson’s neurodegeneration, which severely affects a brain area involved in motor control called the substantia nigra.

A key aspect of Parkinson’s research is to understand new and targeted ways of modulating microglia’s behavior, with a goal of influencing the survival or neurons or nerve cells. Such an ability would help to address the precise link between neurons and microglial cells.

Quantum dots, or nanoscale crystals, can be specifically taken up by microglia cells and may be useful as a direct way of targeting these cells. The nanoparticles also glow a particular color after being illuminated by ultraviolet light, allowing scientists to trace the molecules inside cells and study their cellular behavior.

Researchers at Carleton University investigated whether microglia within the substantia nigra of mice would take up quantum dots alone, and quantum dots carrying an immunotoxin called saporin. The latter works by inactivating ribosomes — cells’ protein builders — which compromises protein synthesis and leads to cell death. The scientists also studied how these nanoparticles affected microglia status (i.e., whether it is active or inactive).

Animals were given a four-minute infusion directly into their substantia nigra of either quantum dots alone, or of one of two doses of quantum dots conjugated with saporin. Within a week post-infusion, the mice’s balance and coordination were assessed.

Using imaging technology, researchers observed that quantum dots alone were selectively taken up by microglia and activated them. Microglia activation is a hallmark of inflammation in the context of neurodegenerative disorders. Despite their activated state, however, microglia had minimal effects on neurons and other neuronal support cells like astrocytes.

But in mice whose quantum dots were administered together with saporin, scientists observed a significant dose-dependent reduction in the number of nigral — meaning “of the substantia nigra” — neurons that produce dopamine, as well as impaired motor coordination six days after the infusion.

Quantum dots conjugated to saporin also increased the levels of a molecular mediator of inflammation, called WAVE2. This protein “is critical for the changes in activation state morphology of microglia,” the scientists wrote

The researchers believe that quantum dots carrying saporin could be a new and targeted way of modeling Parkinson’s-related inflammation, and evaluating new therapies aiming to treat it.

“[Quantum dots] might be a viable route for toxicant delivery and also has an added advantage of being fluorescently visible,” they wrote.

“Future work using this model should attempt to establish various degrees of neuronal loss. This model could then be used to test neuro-recovery or protective agents at differing stages of [the disease],” the researchers added.