#SfN14 Day 2: On the Origin of Sex Differences in the Brain (Theme E)

This post is part of my series on the 2014 Society for Neuroscience annual meeting. You can read other posts in this series here. I’m also live-tweeting some sessions @GainesOnBrains. Join the conversation at #SfN14.

This is what a bunch of hungry neuroscientists look
like when it's 5pm and the poster session is over.

One of my mentors likes to occasionally tease me when I bring him data: “You’ve discovered something new. Men and women are different.”

He kids, of course. Male and female brains are different in funny and fascinating ways we don’t quite understand.  My poster (which I presented this afternoon) was on gender differences in the loss of slow-wave sleep across adolescence. I just had a paper accepted (today, actually!) on gender differences in some aspects of sleep apnea. (I could actually probably build a pretty successful career on studying gender differences in sleep alone, actually. If I wanted to.)

So I was very excited to attend Dr. Margaret (Peg) McCarthy’s talk on the origin of sex differences in the brain earlier this afternoon.

Let me get two things out of the way before I begin. First of all, I really admired Dr. McCarthy, who hails from the University of Maryland School of Medicine, for how she spoke about her past and present colleagues, giving credit where credit was due to previous labmates and graduate students. You don’t realize how few people do that until someone does it explicitly.

Secondly, McCarthy covered the history of research in sex differences in the most genius way possible: a parody of The Big Bang Theory theme song. Seriously—it was golden.

The simplistic view of biological sex differences goes a little something like this: an undifferentiated group of cells destined to become the gonads will, by default, be ovaries. But it’s the influence of the Y chromosome that gives half of our population testes. In this way, too, the “female brain” is the “default brain.”

So the dogma is simple: sex differences are due to hormonal differences. But McCarthy challenged this notion in three ways. What, other than hormones, is the Y chromosome contributing? How can so many pervasive, multifactorial observations between these gender differences be explained by hormones alone? And how do you explain the convergence and divergence of certain traits in response to homeostatic challenge?

McCarthy’s approach was simple at first; she simply interrogated a single brain region, the preoptic area, to see what she could find. She picked a lucky spot: male rats appeared to have twice the number of dendritic spines, or small outcroppings of the “receiving” end of neurons, compared to females. When females, then, were treated with masculinized estradiol hormone, they, too, developed more spines.

Estradiol worked to induce this synapse formation via prostaglandin E2 (PGE2) synthesis, it seemed. When female pups were injected with PGE2, they developed male-like sexual behavior. Conversely, blocking COX2 in males inhibited male sexual behavior. Amazingly, it took just one injection on the day of birth to stimulate lasting, lifelong changes.

In the years that followed, McCarthy’s lab also examined differences in endocannabinoid tone in the newborn amygdala; differential neurogenesis of hippocampal neurons in neonates; and, what I found most interesting, epigenetic differences that altered sexual behavior without hormone treatment. Some truly fascinating and elegant work. (I encourage you to check out her lab’s website for a publication timeline. You’ll get a good sense of the rationale behind each of their experiments.)

So what’s the big picture? McCarthy says that the sex differences in the brain are unique to each “endpoint” and each region. There are two competing but compatible concepts at play:

1. There’s no such thing as a “male” or “female” brain, per se. It’s all a mosaic, with many regions also being quite “neutral.”
2. The same patterns and magnitudes are observable in almost every endpoint. In the regions McCarthy’s studied, it’s funny—males seem to have almost exactly *twice* of this and *twice* of that compared to females. And you can’t make males more masculine (or females more feminine) by giving them more of hormone X. 

If your system has a sex difference, it should be easy to detect, according to the latter concept. And if this is true, it should be studied! Be warned, because if you’re not doing it, NIH will make you. (Unless you don't want a grant funded, then by all means...)

Tiring day, and not even halfway through. Thankfully this hotel has a Starbucks in the lobby!

Sneaky photo of me explaining my poster. Slow-wave sleep is cool!
I'm about to go have a lot of it right about n-...zZzZz...