Off the Cuff: Jan Thornton, professor of Neuroscience


Courtesy of Jan Thornton

Neuroscience Professor Jan Thornton, who recently published a review of the impact of hormones on the development of Alzheimer’s disease.

Oliver Bok , Editor in Chief

Jan Thornton is a professor of Neuroscience at Oberlin. She recently co-authored a review for Hormones and Behavior with Veronica Burnham, OC ’14 on the way hormones impact Alzheimer’s disease. The review arose from research Thornton presented at the International Congress on Neuroendocrinology in Sydney, Australia.

I should warn you, I’ve forgotten most of the biology I learned in high school.

I started in journalism in college. I started more in humanities, journalism and then actually communications, so I was working in the speech department and then psychology. And I like the humanities and the social sciences and all of that stuff.

So there’s hope for me. I can still be a neuro professor if I want?

Sure. And actually that skill set that I learned back then too is still useful. I am putting out the Neuroscience department newsletter this year. So those things that I learned about in journalism have been useful, I keep using those things.

What made you interested in studying Alzheimer’s disease?

Actually, I’m interested in a combination of biology and psychology, the biological basis of behavior. I’ve had a longstanding interest in that and I’ve studied it from a number of different aspects and a couple different endpoints. Now, for a while I’ve started thinking about [how] gonadal hormones — estrogens and androgens — are important for maintaining the maximal cognitive functioning of humans as well as other animals.

A lot of times there are these sex differences between males and females, and so people have said, ‘So what’s going on with some of those? Are they due to the hormones, or are they due to something else?’ One of those endpoints of cognitive function is memory, and one of those sex differences is actually in Alzheimer’s disease. … Women get Alzheimer’s disease more than men and earlier than men, and it looks like some of that might be because women go through menopause and their estrogens plummet. Whereas for men, their androgens decrease over time but it’s much slower, so they too will get Alzheimer’s disease, but a lot of times it takes a little longer than it does for women because of those estrogens.

So that’s what we’re thinking is going on: Those estrogens will help maintain that cognitive function as we age. … So we’re looking at an aging model — because of what happens with aging and memory loss — as well as [an] Alzheimer’s disease model, as well as actually a schizophrenia model.

I saw that in your research, you’re looking at the luteinizing hormone? What’s that?

It turns out that the whole control of the system — there’s a hormone for the brain that then goes to the pituitary that hangs off the base of the brain — causes a release of LH, or luteinizing hormone. That’s actually the hormone that causes estrogen to be produced in ovaries and androgens to be produced in testes. And then there’s negative feedback. So what those androgens and estrogens do is they keep those LH levels low, so that what happens with menopause is that those estrogens go down, that negative feedback is no longer there and LH levels go very high.

What we’ve been finding is that not only are the estrogens important and the estrogens are acting on the brain to help with memory functions, but estrogens are also important in keeping that LH level low. High levels of LH seem to be rather toxic to the hippocampus, an area of the brain that’s really important for learning and memory. As far as drugs to lower LH, as far as we know, none of those cause cancer. Those don’t have big problems like that, whereas estrogen does.

What kind of models are you using?

We use rat models because of evolution there’s a whole lot of physiology that’s the same across mammals, so they have the same hormones that cause the same kind of effects and they also seem to be very similar in terms of their effects on the brain. Certainly humans are much, much, much, much, much more sophisticated with what they can do with their brains. So rats are kind of a simpler model of simple memory, but there seems to be a relationship there.

How do you elevate the rats’ LH?

We remove the ovaries, the main source of estrogen. In humans, when that’s done it’s called surgically induced menopause.

So broadly speaking, the rats that you give estrogen to show improved memory?

Yeah, what happens is if you remove the ovaries in female rats, their memory gets a lot worse. If you give estrogen [to them], it gets better. But if instead of estrogen you just lower their LH level, their memory is also much better.

Is the LH level a potential cause of Alzheimer’s or simply just one factor?

It’s more of a treatment. It’s not going to be something that cures schizophrenia or Alzheimer’s disease. But right now, as far as Alzheimer’s disease goes, it’s a devastating illness; the baby boomers are all getting older, and we’re getting a lot more people with Alzheimer’s disease. It’s not just devastating for the individual, but for the whole family. And if this is something that really helps maintain one’s memory and the ability to recognize one’s loved ones, it’s going to be a great opportunity to have something that helps out with that.

In your opinion, are researchers making any progress on figuring out what causes Alzheimer’s disease?

Lots of people are looking at it. It’s been one of those tough nuts to crack as far as trying to figure out what’s going on. We don’t know. We know that there’s a lot of increase in a protein named beta-amyloid that seems to be really problematic in terms of causing destruction. One of the things the field is looking at now is inflammation and whether that may be playing a role. We don’t have a good handle on what causes these things or a good handle on how to treat them. And so kind of hitting it at both sides to kind of help things is a strategy that’s often used in science.

How is your research related to schizophrenia?

There’s some interesting correlational work in humans where individuals who have schizophrenia, women who have schizophrenia, tend to report that their symptoms are lower at times when usually their estrogen levels are higher. … Estrogens aren’t going to cure schizophrenia, but the treatments these days are just not as good as we would want them to be. So maybe if we learn more about what’s going on with the estrogens and how they’re acting, we might be able to come up with another tool in our tool belt to be able to help people lessen some of the symptoms of schizophrenia.

What’s next for your research?

We’re continuing to use this model of aging and Alzheimer’s disease to better understand how these hormones are acting on the brain, to again kind of think about potential treatment options. So one of the things we’re looking at is whether these hormones might be acting on what are called neurotrophic factors in the brain, which are these proteins that are involved in maintaining the health of neurons. So that’s one of things we’re looking at.