Stress and myelin structure
Studies into depression and social anxiety have tended to dwell on what the neurones in the brain are doing. But that ignores over 75% of the cells in the nervous system! These are the glia, and they include cells called oligodendrocytes that make the brain’s white matter - or myelin - which invests and nourishes nerve fibres. And the structure of this myelin turns out to be critical to how the brain works and how it defends us against stress. By exposing mice to bullying from more dominant animals, City University New York (CUNY) scientist Jia Liu finds that 60% of them become socially withdrawn in the aftermath, and this is reflected in changes to the myelin pattern in discrete parts of the brain…
Jia - We look at the brain particularly at 'non-neuronal cells', and the reason for is that the current literature has been heavily focused on the role of neurons, and we're trying to tackle this problem from a different perspective: the other cell types in the brain. We particularly look at one type of glial cells, called the oligodendrocytes, which produces a protective coating layer called the myelin. This myelin allows neurons to better and more efficiently communicate with each other, and the oligodendrocytes also provide nutrition and energy to maintain the health of this nerve fibres.
Chris - And what did you look throughout the brain, or did you focus on any particular areas?
Jia - We particularly focused on two brain areas, and one is named 'medial prefrontal cortex' and that is the area of the brain which plays a critical role in emotion and thinking. The other region we also look at, is the nucleus accumbens, which is involved in the reward response; and specifically we look at the number of oligodendrocytes in these two brain regions, as well as the property of the myelin in these two brain regions. The first thing we find is we see fewer number of mature oligodendrocytes and thinner and shorter segments of myelin in the susceptible mouse that display the social avoidance. We only find this in the prefrontal cortex, but not in the nucleus accumbens. When we further investigated by inducing damage to myelin, specifically in the prefrontal cortex, we find this damage was sufficient to impair the social behavior and also when the myelin was restored, the social behaviour was also restored. Therefore we think myelin is also contributing to why there are different behaviours after particular social stress.
Chris - Why do you think that that hypomyelination in the prefrontal cortex causes - or manifests as - a change in social behaviour. Why should it do that?
Jia - We don't directly know the answer to that. What we think is that oligodendrocytes is the cells that produce this myelin layer, which is known to help the neurons to better and more efficiently communicate with each other. A proper brain function or proper behaviour output, such as social interaction, will rely on proper communication between multiple brain regions. Such kinds of communication can be manipulated or regulated depending on how the nerve signals propagate from one region to another, and such kind of propagation, especially for example in a medial perfect cortex, which connects so many area of the brain, can be regulated due to the different property of the myelin.
Chris - So how do you think then that the myelin gets changed in this way, because your inputs are behavioural and social ones and it's manifest as a structural change, not so much in the neurons but in the cells that support them. So how do you think the message gets from the nerve circuits onto the oligodendrocytes?
Jia - As a matter of fact, oligodendrocytes also expresses molecules which uses the same type of signal that neurons use to communicate; therefore they're able to receive signals from the neurons to regulate their own molecular properties.
Chris - So do you think then - and I'm speculating wildly I'm being highly provocative with my suggestion - that if we look at humans who become depressed, do you think that at least a fraction of those could well be that there is not so much a neurochemical imbalance in the brain but there might be a disruption, albeit temporary, in the myelin architecture of the brain? And that perhaps some of the therapeutic effect of these drugs we give people is to help the brain actually to remyelinate in a more healthy way?
Jia - I would be happy supporting that! Actually there has been association studies looking at post-mortem tissues from depressive disorder patients which showed that there are differences in the white matter content and what we're hoping to emphasise is that while the current treatment for depression or other psychiatric conditions will target neuronal cell function, perhaps we should also look at other cell types in the brain as the potential causes for stress-related mental disorders.