Imaging Gene Expression in the Brain

An integral aspect of finding better treatment for some of our most intimidating neurological afflictions, like multiple sclerosis (MS) and Alzheimer’s disease (AD), is improving our ability to detect them early. Our capacity to do so has improved drastically with the advent of neuroimaging techniques. But even with neuroimaging, early stages of these diseases may not be discerned if they have not yet caused considerable damage to the brain. What if we could find a way, however, to image the expression of genes that were activated to repair damage done to the brain, however slight it may be? That might be a way to start aggressive treatment of a disease without having to wait for the damage it wreaks to be evident on a brain scan, or without having to do an invasive biopsy.

And it is just what Researchers at Harvard have done recently. Their goal was to be able to detect gliosis in a living brain after damage to the blood-brain barrier (BBB). Gliosis is the accumulation of supporting neural cells called glial cells in areas of the brain where there has been an injury. A particular type of glial cell, called an astrocyte, is involved in gliosis. So, when an area of the brain is injured (in this case, the BBB), one can observe a proliferation of astrocytes in that area. Astrocytes contain a protein, glial fibrillary acidic protein (GFAP), which is integral to their supportive role (more on that in a second).

Since the researchers at Harvard were investigating the brain’s reaction to trauma, they induced BBB damage in mice through a number of different methods. The expectation was that the areas of damage would become engulfed with astrocytes intended to repair the injury. But astrocytes aren’t detectable with standard neuroimaging techniques.

So, the group developed a magnetic resonance (MR) probe that was connected to a short DNA sequence complementary to the mRNA of GFAP. Their reasoning was, if the DNA sequence runs into mRNA that encodes for GFAP, the two will anneal. Remember, GFAP is a protein found in astrocytes. Thus, the probe will accumulate in areas of astrocytic activity. This will be detectable by an MRI and indicate spots where neurological damage has occurred.

That’s exactly what happened. The scientists administered the probe—get this—through an eye drop. That’s about as noninvasive as it gets. The probe accumulated at the places where the BBB damage had been induced. Therefore, the probe seemed to indicate areas of acute neurological damage, before it could be measured otherwise without extremely invasive techniques.

The applications of this could be profound. They could include an improved ability to detect brain damage associated with AD, MS, stroke, and glioma (tumor), among other neurological problems. This could mean earlier detection, and better treatment, which in some of these disorders could mean a world of difference in quality of life after their onset.