October 21, 2020

The Niche

Knoepfler lab stem cell blog

When it comes to brains, bigger is not always better

Humans have big brains, right? In fact, they are downright supersized.

But is that always such a good thing?

As it turns out, no.

Size matters, but bigger is not always better for brains at least.

When I was in high school, my biology teacher had us do the requisite frog dissection and offered extra credit if anyone to dissect out their frog’s brain intact. I managed to do it and found myself with a tiny little smooth brain in my gloved hand. Wow. That made an impression on me.

One of my interests as a ‘grown up’ scientist has been studying how the human brain grows, both normally and also abnormally as a result of birth defects or cancer. I study a gene called N-Myc that is required to direct normal brain growth such that too little N-myc causes small brains and heads (microcephaly). However, too much N-myc is not a good thing as it causes abnormal brain growth in the form of cancer.

p27When we get rid of both N-myc and its family member c-myc in neural stem cells in mice their brains are even smaller and we can see overexpression of the cell cycle inhibitory protein p27 (green in picture above) in the developing cerebellum, a structure in the back of the brain responsible for movement and coordination. Normal cerebella have almost no p27 at this same stage.

I’ve recently done two posts on my lab’s blog that might interest you: Why is the human brain super-sized? and Stem cells on the brain. These posts give background on the how and why human brains are big.

Here I want to talk about why when it comes to brains, bigger is not always better.

During the last several million years, the human brain has grown at a very rapid clip. I would argue that compared to other animals one might rightly say that the human brain is even “abnormally” large. Clearly, evolution has pushed human brain size supporting the argument that not only does size matter, but for human brains bigger is an evolutionary advantage.

There is a price to pay for such a large brain.

One cost of having a big, sugar-hungry brain has been proposed that our big brain is linked to the fact that our muscles are relatively weak. Haven’t you ever wondered why a primate that is roughly the same mass as a human is so strong that it can beat the living heck out of any human, even Arnold Schwarzennegger-sized when he was in his prime? At least in part I think that is a tradeoff we made with Mother Nature. Big brain, girly man muscles as Arnold might put it. Some might suggest he has a girly man brain however.

Another cost is that growing a jumbo brain like ours requires a lot of cell proliferation and stem cells, and one theory says that puts us at increased risk of brain tumors.

It is also true that larger brains do not necessarily equate with more optimal cognition. In fact, it is said that Einstein’s brain was not larger than normal, but perhaps simply organized in a different way. In addition, children with autism frequently have larger than average brains as well. In fact, having a very large head and brain is even considered pathological and called macrocephaly. Interestingly, while microcephaly (small head and brain) is associated most often with impaired cognition so is often (but not always) macrocephaly.

So when it comes to the human brain, bigger is not always better and in fact sometimes it is worse.

Now big ears like Spock…that’s a different story.