Lora D. Weidner, Ph.D., Winner of the 2017 NIMH Three-Minute Talks Competition

Transcript

>> LORA D. WEIDNER: Have you ever twisted your ankle? Or were bit by a mosquito?

You know how your ankle or the area of the bite gets red, puffy, and swollen?

Well, this is due to inflammation - your body's way of responding to an injury and trying to fix it.

Well, the same thing can happen in your brain.

This may seem obvious in cases such as a traumatic brain injury, but inflammation also occurs in diseases such as Alzheimer's and epilepsy.

The problem is, it is possible that in some cases, inflammation can actually worsen the disease.

This is where we come to two enzymes in the brain that are responsible for inflammation: cyclooxygenase 1 and 2, or COX-1 and COX-2 for short.

COX-1 and COX-2 work by converting arachidonic acid - one of those omega-6 fatty acids we are always hearing about on tv - to prostanoids.

These prostanoids then go on and carry out various inflammation-related functions throughout the brain.

Everyone here is already probably quite familiar with COX-1 and COX-2; anytime you take a non-steroidal anti-inflammatory drug, like aspirin or ibuprofen, you are inhibiting the activity of COX-1 and COX-2.

It is also known that COX-1 and COX-2 have different functions depending on where they are located.

Therefore, I would like to know which cells in the brain express COX-1 and COX-2.

To do this, I obtained surgical brain tissue samples from people with epilepsy, and measured the expression of COX-1 and COX-2 amongst 3 types of brain cells: neurons, astrocytes, and microglia.

I used antibodies for COX-1 and COX-2, and for the 3 types of brain cells, put them on the tissue and took images of the tissue with a light microscope.

We can see an example of COX-1 in green, and neurons in red.

From these images, I found that COX-1 is highly expressed in microglia, while COX-2 is expressed in both microglia and neurons.

This is important because most of the attention has been placed on COX-2, but my data suggest that since COX-1 is solely expressed on microglia, the cell responsible for inflammation, it deserves more attention for its role in inflammation.

My future plan is to image the activity of COX-1 and COX-2 in the living human brain.

We can do this using Positron Emission Tomography, or PET imaging.

A PET image is sort of like an MRI, but provides a picture of activity instead of anatomy.

My lab has already developed radiotracers for COX-1 and COX-2 and have used them in monkeys.

Here we can see an increase in COX-2 activity after we induce inflammation in the monkey brain.

So by knowing the cellular localization and the activity of COX-1 and COX-2 in the brain, we can develop better COX inhibitors to treat the underlying inflammation in diseases such as epilepsy.