Sharonda’s Neuroprotection Hypothesis of Depression

I plan to go on one of my strange tangents again! Please forgive me! I read this cool article called “CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis.” Before you walk away screaming “MURDER,” give me a chance to explain. The general idea behind this article was that the immune system (my new favorite thing to talk about—honestly) plays a specific role in generating a microenvironment for baseline neurogenesis. To test this hypothesis, they used T/B Cell KO or mutated mice. They also played with cluster of differentiation (CD4) glycoproteins. This protein is expressed on the surface of T-cells–It’s the reason why HIV can infect T cells. Anyhow, the results suggest that depleting CD4 decreases Brdu+/DCX+ positive cells AND decreases BDNF production in the brain.

What does that sound like? Well, it sounds a lot like our discussions on depression. My question is should we be examining the shift of these immune system populations in depression? I once read a paper that looked at spleen/bone marrow cell populations from socially defeated rats. Most of the results were based on in vitro studies. So, why can’t we talk about immune system abnormalities that shift baseline neurogenesis? Maybe this shift predisposes people to depression.

I also have a big finale! Maybe it is not really a finale… So, the researchers in the immune system paper did a morris water maze test. By the way, Immunologists should get extra brownie points for doing behavioral studies!  Okay, back to the subject!! In the water maze test, they found that CD4 depleted mice have a problem with the reversal learning phase. Let me back up. In this particular study, the test was divided into the acquisition phase (3 days), reversal learning phase (2 days), and the normal probe test. There was no significant difference between the learning curves or the latency to the center for the controls and CD4 depleted mice. When the platform was placed in the opposite quadrant (reversal learning phase), the latency times were significantly higher for the CD4 depleted mice compared to the controls. The researchers suggested that this reversal learning phase tests the ability to reconsolidate/relearn new situations. They eventually explain that neurogenesis is not extremely important in learning and memory, but “to avoid catastrophic interferences in relearning situations.” I think that sentence could drive a lot behavioral neuroscientists crazy, but that is not the point. What if a similar “conclusion” could be made about depression? What if these new neurons protect people from these “catastrophic episodes” that interfere with mood? The inability to create these new neurons might mean that the protection gets disrupted and people experience depression. It could also mean that all of this is under immune system function. Have we heard this before?

Think about it!

Peace,

*Sharonda*

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4 thoughts on “Sharonda’s Neuroprotection Hypothesis of Depression

  1. This would be an interesting theory to try on depression, but what would a relearning example be for depression? Would experiences be dealt with until a certain point where all new situations would not be able to be dealt with in a normal manner? It does make sense however, that memory is not affected by neurogenesis, only new memories are affected.

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  2. FOR THE RECORD, I’m sure there are many flaws in my this hypothesis. That is why I wrote it. 🙂 The idea behind learned helplessness is interesting. Learned helplessness corresponds to a decrease in neurogenesis, right? Maybe the ability to form new neurons actually protects non-depressed people from learning this helplessness? Perhaps in depression, stressful live events causes a depletion of these neurons and promotes learned (relearning) helplessness.

    As for your second point, there might be a threshold for neuroprotection. I don’t know. I honestly think we already have this built-in antidepressant system. This endogenous system becomes ineffective at some point, hence why people need to take drugs to restore the balance. I hope to see this in my senior project/thesis/independent study.

    Their idea about neurogenesis and learning/memory is interesting. They do not CD4 depleted mice (which decreases neurogenesis) should have issues learning the location of the platform in the morris water maze. Surprisingly, both the CD4 depleted mice and the wildtype have the same learning curve. So, perhaps nerogenesis provides neuroprotection, which is the basis of their ‘argument.’ I just applied the same logic to depression.

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  3. I really like this Sharonda-Neuroprotection Hypothesis of Depression to close out the topic! I am probably partial because I am in immunology this semester so am excited to understand the logistics (to a small degree), but also because I really liked the analogy Michael presented in class relating depression to the immune system.

    Also I am curious about the results of the socially defeated rats’ spleen/bone marrow cell populations. (To complement your theory…) Did the socially defeated rats have smaller spleen/bone marrow cell populations?

    Way to be original and thanks for sharing your hypothesis 🙂

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  4. Lisa!! I am so glad you ask the question. It might be a little hard to answer. Based on my hypothesis, I believe that the bone marrow/spleen cell populations should get smaller. Specifically, it is possible that external stress could directly deplete the CD4 populations and cause a decrease in baseline neurogenesis. Thus, those rats would no longer be neurally protected from subsequent social defeat. Now check this out!! This is an abstract from a paper I just found in Pubmed.

    ***********************************************************************

    Title: Changes in Various Measures of Immune Status in Mice Subjected to Chronic Social Defeat

    Abstract: Levels of the major regulatory subpopulations of lymphocytes in the thymus and spleen and blood lymphocyte dehydrogenase levels were measured in male mice with aggressive and submissive patterns of behavior formed over 10 or 20 aggressive confrontations leading to repeated experience of victory or defeat. The results showed that repeated experience of social confrontation non-specifically increased the proportion of segmented neutrophils and lactate dehydrogenase activity in both participants in aggressive encounters, and decreased the numbers of CD4+ and CD8+ T-lymphocytes in the spleen. Succinate dehydrogenase specifically decreased in the lymphocytes of aggressive mice and increased in the lymphocytes of submissive mice. The proportion of CD4+ T-lymphocytes in victims’ thymuses also decreased. Changes in metabolic measures and percentage ratios of lymphocyte contents were dynamic and depended on the duration of confrontational interactions.
    *******************************************************************

    Even the paper that I referenced in my post measured the thymus (the source of T-cells) mass after repeated defeats. Rats in the 6 defeat condition had a significantly smaller thymus mass compared to controls. So, Lisa, there might be something there! I think it is worth exploring :). Maybe I am biased.

    I really REALLY wanted to take immunology this semester. I don’t know much but definitely let me know what you think. Perhaps we can get together and talk a little more about the connections between neurogenesis, immune system, and depression.

    I am also curious about antidepressants now. What if they increase neurogenesis and CD4 populations in the immune system?

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