On the neuroplasticity hypothesis of antidepressant action

By Mark Horowitz

On the neuroplasticity hypothesis of antidepressant action – I worked in a neurogenesis laboratory for 4 years and completed my PhD partly on this topic (For SSRIs). 

We treated human hippocampal stem cells with different combinations of chemicals and looked for neurogenesis with cell markers. 

One of the things that happened often was that the cells died – all or partially. When they all died we re-did the experiments. When it was just partial we used the cells. 

What I had not considered until after my PhD was that one of the major drivers for the growth of new cells is death or damage of cells.

So for example blunt trauma to the head, stroke, haemorrhage and electrical or chemical insult to the brain will cause neuroplasticity/growth of new brain cells, etc. Of course cutting or damaging the skin is one of the main drivers of dermatogenesis as it is in other parts of the body. 

We published a paper last year when a friend of mine treated mice with fluoxetine – half of them had seizures and died and the other half were examined – they had huge amounts of neurogenesis (growth of new brain cells)! This seemed to put damage and neurogenesis directly together.

So when I hear new substance cause neuroplasticity, it makes me think they are probably damaging the brain to produce plasticity. Is it more likely that a synthetic substance is ‘MIracle-gro’ for the brain or that it is toxic to a very delicate organ?