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The Neurogenesis Story

This is a much-too-brief version, in the name of allowing you to get back to whatever chapter you were reading in the Brain Chemistry essays.  With apologies, to Dr. Peter Eriksson and colleagues and the many researchers who have expanded Dr. Eriksson's original findings, for the brevity and simplifications, here goes. Here's a link to their paper, including full text and figures. 

First, to orient you to the hippocampus again, this time we're going to look at it from the front.  Imagine Cindy is standing in front of you and the whole front half of her disappears.  You're looking at the back half of Cindy, still standing there.  Here's what her brain would look like (note the position of her right ear, if you're following me):

     (Cindy's right ear is over here, right?)

 

See the red line to the hippocampus, from the lower left corner?  Of course it looks completely different in this view because instead of looking at it from the side, as we did in the rest of the hippocampus Brain Tour, we've swung around to look from the front.  We're about in the middle of it, thinking from front to back, but now we can see what it looks like inside. This view of the hippocampus is magnified in the next picture:

The red boxes are supposed to mark roughly the same spot in both pictures, to help you keep track of where you are.  (These two pictures are from an essay on hippocampal anatomy at Washington University at St. Louis, which is much more authoritative and thorough than the one you're reading-- but it's all in medical lingo.  There are more superb pictures and explanations, however.  Scroll straight to Section D to see these pictures in their original context, a course for medical students. )

Having come this far, you can finally see now why it's called the hippocampus, from the Greek hippokampos (hippo=horse; kampos=sea monster).  See the curvature, vaguely suggestive of a seahorse? 

Enough anatomy, then.  Back to the neurogenesis story.  The action centers in the dentate gyrus, labeled in the figure above.  Eriksson and his colleagues showed that new cells were growing in this region, in humans.  How did they do this?  Somebody had a very smart idea.  They thought, "hey, there's a cell genesis marker being given every day to cancer patients as part their treatment.  If one of those patients was to die of their cancer, we could look in their brain [they asked permission to do so first]. If they really were making new cells, we'd see that marker show up." 

The marker is called bromodeoxyuridine (BrdU), and it only is taken into cells if they are making new DNA.  Since the only time cells do that, generally, is when they are dividing, the researchers figured that they'd only see BrdU if these patients, before they died, had really made brand new neurons in their brains.  This research, by Dr. Peter Eriksson, was published in 1998 and stunned a whole lot of people, including former medical students who didn't know this was part of the "wrong half" they had learned!   Here are the crucial figures:

The photograph above shows the "granule cell layer" of the dentate gyrus.  Erikkson's research shows that this is where the new cells are formed.  The stain used above will mark the nucleus of any cell.  But the stain in the next two photos below is BrdU, marking the nucleus, indeed the DNA, of these cells -- which indicates that they were "born" after the BrdU was injected.  There they are, right there in the granule cell layer (you can see the ghost-like outline of the same cell shape as shown in the previous slide).

 

Now we'll see this same kind of stain showing the new cells in a mouse hippocampus.  You can see the same kind of pattern, with small labeled nuclei at the edge of the granule cell layer:

Showing that neurogenesis occurs in humans, as well as mice, opened the door to thinking that this might play a role in human neuroplasticity, which has since been shown to be a very central process in mood disorders.  Let's go back now to Chapter 7, picking up the story of neurogenesis and how appears to be involved in depression, and its treatment.