Modelagem realista em neurociência computacional: cadê as glias?
Suponha que existam dois modelos: um modelo detalhado, biofisicamente realista, de uma rede neural sem glias, e uma modelo simplificado, onde os neuronios são representados por elementos excitáveis, porém onde os Astrócitos e Oligodendrócitos também sejam representados por elementos dinâmicos simples. Qual dos dois modelos é mais realista biologicamente?
Sadly, Sci’s home laptop died another little death last night. While Le Petit Mort might indeed feel great to my laptop, the sudden loss of function was pretty rough on Sci. While Mr. S attempts to work his super magic on the issue, Sci’s post for today comes to you via Ruby, Sci’s intrepid little netbook. Everyone wave hello to Ruby, and hope she can keep herself together long enough to get this thing written.
What this also means is that Sci will be unable to provide any interesting pictures until she is capable of getting to her other computer in the AM. She will do her best to paint a picture of this for you in your mind.
First…allow Sci into your mind.
MY GOD YOU HAVE A DIRTY MIND!!!!
Ok, let’s just try and paint a picture instead.
Now picture a rat. One very sad, depressed little rat. Now look at it’s brain. What do you think you see?
Do you see glial loss? Well yes, perhaps…you do.
For some time now, scientists who study depression have noticed that there is cell loss in the brains of depressed patients. Of course, what scientists see in humans is a reduction in brain volume in patients with depression, but does that mean that neurons are being lost? Neuronal connections? And what about those little cells on the side? What about the GLIA?!
Glia have been something of a black box to scientists until recently. At first, we thought they were just support cells, helping with reuptake and metabolism, forming myelin sheaths to allow for quick transmission of information, and giving neurons the supportive environment that they needed to thrive.
But is that really ALL they do? After all, glia outnumber neurons 3 to 2! (Oh hey, look I rhymed!) And it turns out that glia may have important roles in helping to control neurotransmission, though as of right now, scientists aren’t at all sure how they do it.
Now, scientists DO know that both glia and neuronal density is lower in patients with depression. The question is, are the decreases in glia themselves important? Or are they only important in the context of the neurons they support?
So in an effort to get at this question (Sci will go on to whether they really GOT at this question in the end), the scientists took a bunch of rats. They then did three different things to them:
1) They had the rats undergo a chronic, unpredictable stress. These are 10 different mild stressors that are given several times a day for a while. You’d be surprised what stresses out a rat, it includes things like tipping the cage one way or the other, raising or lowering the temperature, turning the lights on and off, strobe lights, taking the food away for a few hours, stuff like that.
2) They used the toxin L-Alpha-Aminoadipic Acid (L-AAA) to selectively get rid of astrocytes, a specific kind of glial cell, in the prefrontal cortex. This would selectively block the function of astrocytes for a few days.
3) They used another toxin, Ibotenic acid, which hits only NEURONS, as opposed to one that hits glia. This would divide out the effects of the neurons in depression vs the ones in the glia.
And here’s what they came up with:
1) They found that the chronically stressed rats had LESS GLIA than unstressed rats. This meant that the stress itself reduced the glia. These rats also displayed behaviors that scientists look at to characterize depression. They drank less sucrose and took longer to approach a tasty bit of food. They even didn’t swim as much in the forced swim test. The depressive like behaviors correlated with a decrease in glia.
2) They found that getting rid of astrocytes using L-AAA gave the same behavioral effects as the chronic stress procedure. The rats drank less sucrose and swam less, showing depressive like behaviors. These rats weren’t stressed, they were just missing glia.
3) This was a test where they infused a neurotoxin to just delete neurons rather than glia. This time, they DIDN’T get any depressive behaviors, which suggests that the depressive behaviors seen above were entirely the result of the deletion of the astrocytes, NOT a deletion of the neurons!
So what does this all mean? Well, it could mean that the important loss in depression is loss of the glia, not loss of the neurons. The neurons ARE lost, but that could be because of loss of the glia, which means loss of a neuronal support network.
Sci thinks this paper is a nifty little bit of research. It’d be interesting to see if all models of depression cause a loss of glia, and it’d ALSO be interesting to see if antidepressants INCREASE levels of glia. We know that antidepressants increase levels of neurons, but do they also increase levels of glia? Would increasing glia be more effective than neurons?
I think more work is needed. Sigh…every time you think you’re getting a handle on the brain, it just gets more complicated. First neurons, then neurotransmission, now GLIA?!
BANASR, M., & DUMAN, R. (2008). Glial Loss in the Prefrontal Cortex Is Sufficient to Induce Depressive-like Behaviors Biological Psychiatry, 64 (10), 863-870 DOI:10.1016/j.biopsych.2008.06.008