Mind the Gap: The Synapse and Why It Matters

Ketamine has been used for decades as an anesthetic. It is also an analgesic and a potential hallucinogen. How does this strange drug work to alleviate symptoms of depression?

In an age of burgeoning developments in molecular medicine, the evidence points to some exciting answers. Ketamine seems to heal the damage done to the brain’s synapses by depression and severe stress, and to do so within a matter of hours.

The word synapse first appeared in Foster and Sherrington’s 1897 Textbook of Physiology. It was suggested by English classicist Arthur Woollgar Verrall and comes from the Greek synaptein meaning “to clasp, join together, tie or bind together, be connected with.” In the brain, synapses are the junctions between cells at which molecular signaling takes place.

Neurons are not unlike ourselves: if they can stay in healthy relationship with one another, connected, communicating, then their world, the brain, can thrive. Stress or depression, however, breaks those connections, damages individuals and the world they inhabit, disrupts communication. When depressive illnesses take hold, in more ways than one, the mind goes dark.

Researchers Ronald S. Duman and Nianxin Li wrote in the abstract for a 2012 paper, ”We have found that ketamine, an [NMDA] receptor antagonist, causes a rapid induction in synaptogenesis and spine formation in the [prefrontal cortex] via stimulation of the [mTOR] signaling pathway and increased synthesis of synaptic proteins.” In other words, what ketamine does is rebuild broken synapses. It increases the synthesis of synaptic proteins – the building materials needed for structurally sound synapses – and reverses the atrophy of neurons caused by stress and depression. As shown in the image from Duman’s laboratory that has become an instant classic in this field of research, and as described by N.I.H. researcher Carlos Zarate, ketamine can make neurons that once looked like dead trees in winter look like blooming trees in spring again (image source here):

 

 

It’s sometimes said that “the space between” is what matters most. It’s where things are set in motion, where fruitful exchanges can happen. Ketamine targets that space on a molecular level: it can be a powerful contributor to synaptic plasticity and synaptogenesis. Simply put, at the appropriate doses it has the potential to restore the structure and function of patients’ brain cells and offers, for many, the possibility of resetting and restoring their lives – and without the six-to-eight-week wait required by so many oral medications. Spring is no longer just around the corner. It’s here.

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