Feathered Friends Help Scientist Learn about Tobacco

True or false: Nicotine is bad for you.

No matter how you answered, you're correct. Nicotine is good for you. And bad for you. It all depends, at least in part, on the age at which you are exposed to nicotine.

It's a medical mystery that FSU College of Medicine Assistant Professor Susanne Cappendijk is trying to unravel with the help of the MagLab's 900 MHz magnet and some fine, feathered friends.

Cappendijk has been researching the long-term effects of drugs such as nicotine on the brains of zebra finches. Why zebra finches? Turns out these beautiful, bitty birds, weighing in at around 15 grams, have to learn to sing in a way not unlike how babies learn to talk. The areas of their brains involved in song learning and memorization (cognitive functioning) are similar to comparable structures in humans. Also, these animals mature relatively quickly: Within 90 days after hatching they are sexually mature. So, long-term studies in finches can be performed in a shorter time span than studies with rodent and primate models.

In pregnant women, nicotine readily crosses the placenta and induces growth and neurobehavioral abnormalities (disturbed cognitive functioning) in their children. Those deficits persist at least up to 1 year of age, according to some studies, while other studies suggest they may continue into late childhood or adolescence.

In contrast, research has shown that nicotine can actually enhance memory and other neurological processes in patients suffering from neurodegenerative disorders such as Alzheimer's disease.

Cappendijk's finches are helping her figure out why young and old brains respond so differently.

"What we are doing in my lab is trying to search for the underlying mechanisms of actions in the developing zebra finch brain," she says. "Why is [nicotine] so damaging when you are young and developing your brain, while when you are, for example, an Alzheimer's patient, it's beneficial to your brain?"

Working with the MagLab's Sam Grant, an assistant professor of engineering at the FAMU-FSU College of Engineering, Cappendijk examines finches before and after injecting them with the drug. She monitors various changes, including behavior, movement, song patterns, eating and weight. She also looks at what's going on in the brain: That's where the MagLab's "900" comes in, the most powerful MRI machine in the world.

In the 900, Cappendijk scans the finches' brains before injection, and then brings them back a few weeks later. "We rescan the animal and then we have two templates we can put on top of the other, and we can see how nicotine can affect brain nuclei," she explains.

"I can see that a volumetric change in some brain areas occurs using the 900, but I can't see what the change is due to," Cappendijk says. To answer that "why" question, the animal must be sacrificed and its brain examined. Cappendijk and her students look for genetic changes and for the neural pathways nicotine is acting on, which potentially differ for young and old finches.

For a magnet of its strength, the 900 has a very large experimental space – plenty big to fit live finches. This not only allows Cappendijk to design better experiments, it also decreases the number of birds she needs to sacrifice.

"Before I had the option of going to the 900, I had to sacrifice animals before [injection] to make a baseline, and I had to sacrifice animals after," Cappendijk explains. "But the problem is that an animal is not its own control, so there could be an inborn genetic difference present, which might affect the data interpretation. Using the 900 allows us to use an animal as its own control, which is very important."

Cappendijk says these studies, funded by the James and Esther King Biomedical Research Program, the First Year Assistant Professor Grant Award and FSU's Department of Biomedical Sciences, will lay the foundation for her long-term research goal: contributing to the understanding of the role of the nicotinic receptors in age-related neurodegenerative disorders and examining how nicotinic therapies can treat these disorders, without the toxic side effects of nicotine.

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