Comments on: Increased neurogenesis is not (necessarily) the opposite of reduced neurogenesis

By: Jason Snyder

Jason Snyder — Sun, 26 Dec 2010 19:48:22 +0000

Mmmm, no.

By: Mr.X

Mr.X — Mon, 06 Dec 2010 22:43:06 +0000

Hi Jason, I have an question for you. So basically your theory states that if brain exposed to high levels of stress would be also exposed to excessive neurogenesis enhancement
(by medications, cannabis etc;) in right areas of the brain it may cause neuronal growth which would positively affect behavior, memory and learning. Is there anything you want to add about this particular paragraph?

Thanks. Mr.X

By: Jason Snyder

Jason Snyder — Thu, 18 Nov 2010 16:25:15 +0000

Definitely there’s no absolute number of new neurons that is ideal for each animal but instead I’d propose that the optimal number of new neurons depends on how many the animal needs to maintain some sort of behavioral homeostasis. For example, say that learning increases neurogenesis and that these new neurons take part in storing this new information permanently. You could argue that as an animal ages it learns more and more about the things of the world, and less and less exists for that animal to learn about in the future. And so neurogenesis is reduced accordingly. An animal that learns more than average during early life may therefore have reduced neurogenesis later in life (and vice versa) – their optimal levels of neurogenesis are different. Take this sort of thinking and apply it to stress, nutrition, social factors etc. and you’ve got a lot of hard-to-tease-apart variables controlling the levels of neurogenesis!

By: Carlos Fitzsimons

Carlos Fitzsimons — Mon, 15 Nov 2010 20:43:12 +0000

Hey Jason,
to continue with the discussion “more-neurogenesis-is-not-always-good”, it would be interesting to note that in animal models of Alzheimer’s , increased proliferation and in some cases increased survival of new neurons has been observed (Haughey 2002 (2x) and Mirochnic 2009, a.o.). I shall say these observations add to the idea of the need to restore neurogenesis levels to normal (whatever that may be) instead of increase or decrease it in absolute terms. What rises the question of how to define normal levels, of course. This is, how (or where) would you place the y=0 in your graph above?
Cheers,
Carlos

By: Jason Snyder

Jason Snyder — Fri, 18 Jun 2010 15:59:05 +0000

Hey Carlos – I wasn’t super clear there at the end – I do agree there are ways to increase neurogenesis but the key is *selectivity*. Running increases neurogenesis but it has so many other effects on the brain that you can’t isolate the neurogenesis-specific benefits.

Your ideas with respect to seizures bring up a good point – that greatly-increased neurogenesis could be bad. Or maybe too much neurogenesis in an unhealthy (e.g. epileptic) brain is bad (creating a U-shaped curve) but in a healthy brain has little effect (creating the sigmoidal curve shown so artistically, above).

(BTW, I would argue the Jessberger paper doesn’t show increased neurogenesis is detrimental – they just show that new neurons are integrating differently in the epileptic brain. This altered integration could certainly be bad but, as Jakubs 2006, speculated, it may actually be an attempt to homeostatically restore normal functioning. I feel like someone *must* have looked at seizure susceptibility in normal and neurogenesis-deficient animals…)

Thanks for the ideas!

Jason

By: Carlos Fitzsimons

Carlos Fitzsimons — Fri, 18 Jun 2010 15:25:09 +0000

Dear Jason.
I have been reading extensively this entry of yours and although I agree in the point you are trying to make (i.e. decreased neurogenesis as opposite to increased neurogenesis, both compared to basal levels) I am not sure I absolutely agree with your affirmations. First of all, there ARE means to increase neurogenesis beyond normal levels: running; and even beyond “healthy” levels (whatever that means). For instance, almost everything that induces seizures affecting the hippocampus (i.e. kainic acid) will increase neurogenesis as compared to basal levels (i.e. Jessberger S, et al., J, Neurosc., 2007) and particularly in this model it has been demonstrated that too much neurogenesis is actually deleterious to the hippocampus.
All in all, I think that it would be quite safe to speculate that, to the contrary of what the press suggested, the problem is not as simple as it looks like ( is ever?) and that there is a adequate physiological level of neurogenesis that whether decreased or increased will affect its normal functions.
So, one should aim to revert or correct neurogenesis (no normal, relative levels) but never to increase or decrease it (in absolute terms) . Based on this I would suggest that your model needs to adjusted to a inverted U-shaped curve.
I will be very happy to hear your opinion on this
Carlos