Thursday, September 23, 2010
In 1998, Dr Gage's lab turned neuroscience upside down by discovering that human beings are capable of growing new nerve cells throughout life, a process called neurogenesis. Following from this, Dr Gage found that environmental stimulation and exercise can promote brain cell growth.
Dr Gage's work has literally changed how all of us think about the brain and mental illness and recovery. Soon after, for instance, Ron Duman at Yale found that antidepressants can promote brain cell growth and Husseini Manji, then at the NIMH, found that lithium can act as brain fertilizer.
Together, these and other findings caused researchers and clinicians to rethink mood disorders. Dead or atrophied brain cells, for instance, may compromise entire neural networks. Neurons cannot efficiently communicate with other neurons. Thinking and feeling and perceptions become distorted, resulting in all manner of personal catastrophes.
Looking deeper inside the neuron, we find that various complex bio-chemical processes responsible for the cell's maintenance may be on the fritz. Of special interest are signal transduction pathways, which interact with incoming and outgoing signals from neurotransmitters.
Thus, if a key signal transduction pathway is down inside the neuron, the cell may lack the means to communicate with other cells. The cell may literally shrivel up and drop off the grid. We know that stress can be particularly toxic to nerve cells. Over-excited neurons literally buckle under the load.
But, thanks to Dr Gage, we know the process can be reversed. Physical exercise can regenerate brain cells, as can living in enriched environments. As can certain medications. In other words, we are not stuck with the brains we are born with. Neither are we hard-wired for life.
Neurogenesis takes place in the hippocampus, which is involved in both emotion and memory. Hippocampal neurons are also intimately wired into other areas of the brain. Dr Gage and his team found that not only do new brain cells grow here, but that these new cells can join neural networks.
Dr Gage's work may explain why it takes antidepressants at least several weeks to produce results. In theory, an SSRI should work almost immediately. But if these meds are involved with the complexities of brain cell growth and restoring neural networks, then obviously we are talking about long lead times.
This has led researchers such as Dr Manji to focus on new meds development that can more precisely target pathways inside the neuron (rather than neurotransmitters outside the neuron) and thus significantly reduce lead times. In the meantime, Dr Gage's work has encouraged patients to take a more active part in their own recovery by doing what we know is good for us, namely: be mindful of stress, make sure we are actively interacting with the world around us, and exercise.
I walk across the Salk Institute campus to a large building and find my way to Dr Gage's lab. Dr Gage greets me and leads me to his small office. He has a much larger office upstairs, but here is where he actually works. He apologizes for his casual attire and ducks in a back room to change into an emergency white shirt.
On a white board behind his desk is a very complex diagram of blobs and squiggles, apparently representing something going on inside the neuron. I spot three letters - Wnt - and joke to Dr Gage that I think I actually know what something on his rendering means: Wnt (pronounced wint) signaling pathway.
My knowledge of brain science is largely derived from hearing brain scientists such Dr Gage (I heard him three years ago at a conference) dumb down their presentations for psychiatrists. That way I can almost understand the broad outlines of what is going on. Trying to make sense of brain scientists talk to brain scientists is Mission Impossible.
Dr Gage is curious about where I fit into the picture, and when I tell him how I'm coping with my illness with very little use of meds, with no hesitation he replies, "good." A psychiatrist would have hesitated. I tell him that moving to southern California nearly four years ago did wonders for me.
Enriched environment, exercise - where have I heard that?
Dr Gage will be in London during our Awards Dinner and will be honored in absentia. I'm here to get a minute of him on film, for showing at the dinner. Dr Gage has received no end of high honors from the research community. He was also recognized by Time Magazine as one of the 100 most influential people of 2000. But he is also very clearly flattered that people like us are paying attention, and this comes across loud and clear with the camera rolling.
We finish shooting, then he escorts me outside, where we stroll across the campus engaging in small talk. I ask him if being at the Salk Institute means he doesn't have to worry about where his funding is going to come from, but that is not the case. Like researchers everywhere, he is responsible for raising literally every penny, including his own salary. He says this helps keep him on his toes and keeps his lab lean and mean (he has some 45 researchers under him), but then he adds he's looking at things from the glass half full.
Thus, in my view, the vital importance of bringing our world and Dr Gage's world together. Enlightened research can only flourish with an enlightened public. We shake hands. It's time for him to return to his world, and me to mine. But I cherish those precious moments when our worlds connect, and I'm looking forward to those attending our dinner getting a little taste of it.