New neurons and a new therapeutic target

The recent discovery that the human brain produces new neurons throughout life has led us to re-evaluate how we think about our brains and their plasticity, as well as examine potential new targets for psychiatric treatment.

In the narrow space between your ears, a roughly three-pound lump of tissue (composed mostly of water) contains everything that makes you who you are. Your brain is responsible for all of your memories, emotions, actions and aspirations. The human brain is also the source of all of our joy and misery, and understanding its workings offers hope for the amelioration of psychiatric suffering and, possibly, greater potential for happiness and enjoyment of life. However, one difficulty in dealing with the complexity of psychiatric disorders is that frequently multiple theories arise to help explain the origin or cause of any particular condition.

Depression is one example of this; there are many hypotheses attempting to explain this debilitating condition that affects more than 120 million people worldwide. One of the most widely-known theories is the ‘monoaminergic theory’ of depression, which focuses on neurotransmitters (chemicals used by neurons for communication) like serotonin. However, in this entry I will try to give a brief review of a more recent theory, the ‘neurogenic theory’ of depression.

Up until relatively recently, it was believed that the brain stopped producing new neurons after development; as the famous neuroscientist Santiago Ramon y Cajal said around a century ago, “In the adult centers, the nerve paths are something fixed, and immutable: everything may die, nothing may be regenerated”. However, in 1998, the creation of new neurons in the mature brain, a process known as ‘adult neurogenesis’, was confirmed in humans. This experiment, led by Fred Gage at the Salk Institute, looked at the postmortem brains of cancer patients who had been injected with a compound used to ‘label’ the DNA of cells about to divide. This compound (bromodeoxyuridine, commonly called BrdU) was used in these patients to evaluate (peripheral) tumor proliferation. But as BrdU crosses the blood-brain barrier, Gage and colleagues cleverly used this labelling to show that new cells had also proliferated in the brain, and that a number of these cells had differentiated into mature neurons. BrdU is now commonly used (including here at the Douglas) to study adult brain neurogenesis in animal models.

But there are some mysterious aspects to this phenomenon. For one thing, there initially seems to be only two clearly neurogenic areas in the brain; the olfactory bulb, and the dentate gyrus of the hippocampus. There’s some early evidence to suggest other parts of the brain may be neurogenic as well, but even in these areas, the number of new cells produced seems to be limited at best. So this raises some questions; why just these few areas in particular, and not others? And what is the function of these new cells?

Although adult neurogenesis is still a relatively new discovery, it’s become something of a hot topic in neuroscience, so we have some preliminary answers to the questions I just posed. For one thing, these new neurons seem to have special properties, in that immature neurons seem more ‘plastic’ or flexible in their firing responses than other cells. We also have some hints at their function, particularly with hippocampal neurogenesis; it’s been shown to be involved in learning and memory and, most importantly for this entry, has been associated with emotional functioning.

This brings us back to the neurogenic theory of depression, an idea that essentially states that if the rate of production of these new ‘special’ neurons decreases, depressive symptoms may appear or be increased in severity, whereas increases in the rate of adult hippocampal neurogenesis can reduce the severity or appearance of depressive symptoms. Although this idea is only a few years old, there’s some evidence supporting it. For one thing, factors that seem to make depression worse, such as stress, also decrease hippocampal neurogenesis, and factors that have been shown to improve depressive symptoms, such as antidepressant drugs and electroconvulsive treatment, also increase hippocampal neurogenesis. Human depressed patients also show decreased volume of the hippocampus. In addition, the delay between starting antidepressant medication and the amelioration of depressive symptoms, roughly four to six weeks, closely mirrors the time necessary for newly-proliferated cells spurred by these medicines to develop into functional neurons. And finally, experiments using animal models have shown that factors that increase neurogenesis also induce antidepressant behaviour.

So the neurogenic theory of depression, although it’s still a relatively new idea, has the potential to offer some exciting insight into depression and other psychiatric conditions, including treatment applications; if increasing the rate of neurogenesis can improve depression and depressive symptoms, then we can potentially develop new medications and treatments aimed specifically at increasing adult neurogenesis.

It’s important to keep in mind that a lot of the theories scientists have developed concerning psychiatric illness are still preliminary, and a lot of important research is still needed before we can provide the definitive answers patients and their families are desperate to hear. However, the silver lining is that with the work of researchers and clinicians here at the Douglas and elsewhere, we’re constantly getting closer to finding those answers, and offering hope to those searching for it.

[An abridged version can be seen here.]

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Posted in Antidepressant, Depression, Neurogenesis, Neuroscience, Psychiatry, Public Education.

Posted on 21 Oct 2010

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8 comments to New neurons and a new therapeutic target

  1. Cam Zacchia
    On Oct 22nd 2010 at 13:53

    Since the hippocampus is most involved in emotional memories (correct me if I’m wrong), neurogenesis in the hippocampus seems to suggest that the brain needs to be more adaptable to emotional cues and changes than it needs to be in other areas of learning. This does make sense since fear and other emotions are more responsive to immediate situations and dangers. In other words, our brains had better learn quickly and remember the link between a situation and the emotion it elicits in order to ensure survival.
    If “need to adapt” is behind neurogenesis, one would expect more of it in all parts of the brain involved in learning and memory (i.e. a little of it everywhere, but more of it in specific structures).
    Amazing work.

    • Ian Mahar
      On Oct 24th 2010 at 16:33

      Actually it depends on which part of the hippocampus you’re talking about; there’s good evidence to suggest that the ‘dorsal’ part of the hippocampus is mostly involved in spatial learning and memory, and the ‘ventral’ part is more involved in emotional modulation. As for fear learning, the structure most associated with that function is the amygdala, and in fact people are currently investigating whether neurogenesis occurs there, too. Thanks for the comment!

  2. calonne
    On Mar 17th 2011 at 20:39

    This blog is a good idea!!!

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  4. Gerald Lemaire
    On Sep 12th 2012 at 22:55

    Dr. Ian Mahar, I recently read Dr. Norman Doidge book: “The Brain that changes itself”. Dr. Doidge’s works is opening hopes to my wife and me. – I’m 80 year young, and while I’m not a trained medical person, my four battles with depression (the last one 18 years ago) entitle me to speak (intelligently, I hope) on the subject. – My wife (53 year young) went through more severe depression episodes. – A cocktail of prescribed pills minimally allows her a certain quality of life.
    My hope: Finding in Montreal, a mental heath specialist (hopefully French speaking) whom would be familiar with the approach described in Dr. Doidge’s book.
    Dr. Mahar, Could you please direct us to the right people?

    • Ian Mahar
      On Sep 18th 2012 at 21:05

      First of all, thanks for your comment. I am not a physician (I’m a PhD candidate), and so unfortunately I cannot personally provide medical advice or referrals; however, you may find resources on the Douglas Institute’s website, including the “Need help?” section at the top of the page. Best of luck to both you and your wife in the future!

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