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Recent research has shown that levels of serotonin in the brains of HD mice are lower than normal. A common and effective way to increase the amount of serotonin in the brain is by prescribing a class of drugs known as selective serotonin reuptake inhibitors (SSRIs).

How do SSRIs work?

In order to understand how SSRIs increase the amount of serotonin signaling in the brain, we must first understand how neurotransmitters like serotonin work. Neurotransmitters are important molecules in the brain that help nerve cells communicate with each other. A message is passed within a nerve cell electrically, but when it comes to the end of the nerve cell and the message must be passed to another nerve cell, the message must be converted to a chemical signal. This is where neurotransmitters come in: they are the chemicals that carry the message between nerve cells. The space between two nerve cells is called the synapse. The nerve cell that is sending the message is called the presynaptic cell and the nerve cell that is receiving the message is called the postsynaptic cell. When the presynaptic cell gets the signal to pass on the message, it releases the stored neurotransmitters into the synapse. Once in the synapse, the neurotransmitters can be taken up by receptors on the postsynaptic cell, and the message begins to be passed through the new cell. In order to prevent too much signaling, the neurotransmitter cannot stay in the synapse for too long. The presynaptic cell begins to take back the neurotransmitter, storing it for the next time that a message needs to be passed across the synapse. This recycling of neurotransmitter is called “reuptake.” (For more information on the neurobiology of HD, click here.)


When the nerve cells of the brain produce less serotonin, there is decreased serotonin signaling. Serotonin signaling is decreased simply because there are not enough serotonin molecules to interact with the receptors on the cells. Instead of figuring out how to make more serotonin, the amount of serotonin signaling can be increased by preventing the reuptake of the neurotransmitter back into the presynaptic cell. By allowing the serotonin more time in the synapse, there is a better chance that the proper amount of interactions will occur with the postsynaptic cell to pass on the message. This mechanism is where SSRIs come in: they block parts of the presynaptic cell so that less serotonin can be recycled, allowing it to spend more time in the synapse to pass on the signal.