schmuck schmaltz schmendrick: Pink Medley

neurolove:

Depression and the brain

I’ve gotten questions about depression and what causes it, so I thought I would start talking about that- and I would start at the very small cell-level (and move out to brain regions, etc in later posts).  It’s important to note that diagnostically, depression is a disorder of exclusion, meaning that if a patient fits the rather vague and varied symptoms and doesn’t seem to meet the diagnosis for anything else, they can be classified as depressed.  For instance, depression can be indicated by eating too much or eating too little; sleeping too much or not sleeping enough; etc. It is a catchall, and therefore, there are a lot of theories about how it might manifest, and it probably manifests in different ways in different people.

One theory I am finding particularly interesting and which seems to have growing evidence is that depression involves glia.  In the diagram at the top from a recent paper in the journal, Current Opinion in Cell Biology, the Duman lab has diagrammed the way that they think the glial cells, astrocytes, play a role in depression.  Astrocytes reuptake glutamate, an excitatory neurotransmitter, after it has been released by neurons and break it down to its precursor glutamine, which they feed back to the neurons so that they can make glutamate again.  Depression seems to involve decreased numbers of these astrocytes.

On the other side of the diagram, they also show that there seem to be decreased numbers of GABAergic interneurons, which provide critical inhibition of glutamatergic neurons. (GABA is typically, as it is here, an inhibitory neurotransmitter.)  This means that there is decreased reuptake of glutamate by astrocytes and decreased inhibition of glutamatergic neurons in depression.  Too much glutamate can lead to (and seems to in depression) excitotoxicity.  This means neurons are being stimulated/excited too much, and this can lead to their death (the toxicity part of excitotoxicity).

I find this particularly interesting because it suggests a role for glia other than just neuronal support- they actually seem to be contributing to disease/disorders when they are missing and may play even a bigger role as we learn more about them.

[Image Source: Banasr M, Dwyer JM, & Duman RS (2011). Cell atrophy and loss in depression: reversal by antidepressant treatment. Current opinion in cell biology, 23 (6), 730-7 PMID: 21996102]