Past Winner
2002 NSERC Doctoral Prize

Ashley Monks

Psychology

Simon Fraser University

A Canadian researcher has uncovered molecular evidence for how sex hormones work to actually rewire the adult brain and various motor neurons.

It's groundbreaking research for which Ashley Monks, a recent Simon Fraser University psychology graduate, is being awarded a 2002 Natural Sciences and Engineering Research Council Doctoral Prize — one of Canada's premier graduate student awards.

Dr. Monks' research was the first to demonstrate that sex hormones, including testosterone and estrogen, regulate the expression of N-cadherin in the central nervous system.

Cadherins are a group of cell adhesion molecules thought to regulate cell development, including the creation of neural synapses, the connections between nerve cells.

Prior to Dr. Monks' work it was widely thought that cadherins were primarily associated with cell differentiation during early development, and were only present in the adult nervous system in low and static levels.

However, in conjunction with his thesis supervisor Dr. Neil Watson, Dr. Monks has demonstrated that, in rats, sex hormones trigger the production of N-cadherin, which is responsible for remodeling key components of the central nervous system — including copulation-controlling motor neurons and the hippocampus in the brain.

"When we treated castrated rats with testosterone, we found increased N-cadherin expression along with a 40 per cent increase in the number of synapses in the motor neurons that control the rats' copulatory reflex. This suggested a link between N-cadherin and synaptic density," says Dr. Monks, who's continuing his research as a Canadian Institutes for Health Research postdoctoral fellow at Michigan State University.

There are significant differences between how the nervous systems of male and female rats respond to sex hormones, says Dr. Monks. In general, N-cadherin expression tends to occur more rapidly in females, and a greater range of nerve types respond.

By tracking N-cadherin production through the estrus cycle, the researchers were able to link both its level of production and the neural connections that were being made and unmade to the natural fluctuations in sex hormones at the various stages of the cycle.

The findings were published in the prestigious Proceedings of the National Academy of Sciences of the United States of America last year.

Dr. Monks notes that the research raises important questions about the role of hormones and behaviour in humans. It also suggests a possible new medical concern about the increasing use of sex steroids in practices such as hormone replacement therapy.

"There isn't enough appreciation of the effects that sex hormones have on the nervous system in adults," says Dr. Monks. "The idea that neurons have a certain shape and don't change doesn't hold up. It looks like they do change and quite rapidly. Hormones really do affect how the brain is organized."