I’ve read that patients start showing Parkinson’s symptoms (tremors, muscle rigidity, etc.) when 60-80% of dopamine-producing neurons have died. (The ten-buck medical term for dopamine-producing neurons is “dopaminergic neurons”.) So this started me wondering….
–How many dopaminergic neurons did I start out with?
–How many neurons do I have overall? What percentage are the dopaminergic neurons?
–How come the brain doesn’t just produce more dopaminergic neurons?
All answers turn out to be very complicated, and immediately plunge you down the rabbit hole of neurologic scholarly journals. The question about the total number of neurons is the most straightforward to answer. For a long time, neurologists estimated the brain contained 100 billion neurons — a suspiciously round number. However, as reported 2/28/12 in the UK newspaper, the Guardian:
” ..When a researcher in Brazil called Dr Suzana Herculano-Houzel started digging, she discovered that no one in the field could actually remember where the 100bn figure had come from – let alone how it had been arrived at. So she set about discovering the true figure….This involved a remarkable – and to some I suspect unsettling – piece of research. Her team took the brains of four adult men, aged 50, 51, 54 and 71, and turned them into what she describes as “brain soup”. ” (The men, needless to say, were cadavers.)
Doing analysis that the article did not detail (and you probably don’t want to know anyway), Dr. Herculano-Houzel came up with the revised estimate of 86 billion neurons —still a comfortingly large number.
So how many of these neurons are dopaminergic neurons? I came across an article from way back in 1991 (the Stone Age in rapidly changing Parkinson’s research) that put the number of pigmented and non-pigmented neurons in the substantia nigra (a stand-in for dopaminergic neurons) at a measly 810,000 (550k+210k). Here’s more info from the abstract:
“Using an unbiased stereological technique, the total numbers of pigmented and non-pigmented neurons were estimated in the substantia nigra of seven patients with Parkinson’s disease and seven control patients. Compared with the controls, in which the average total number of pigmented neurons was 550,000, the number of neurons was reduced by 66% in the patients. The average total number of non-pigmented neurons was 260,000 in controls and reduced by 24% in the patients… The stereological estimates made in this study are unbiased, in that they are independent of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures.”
If I’ve done my math right, the dopaminergic neurons are 0.00094% of the total 86 billion neurons. It’s amazing to me that this tiny sliver of neurons can cause so much trouble!
So for the final question: How come the brain doesn’t just produce more dopaminergic neurons? Wouldn’t this be like the body producing more white blood cells when there is an infection? Of course, when you’re dealing with the brain, it’s never that simple. For a long time, scientists thought the number of neurons was fixed at birth. Then, as Dr. Wikipedia diplomatically puts it: “Studies in the 1990s finally put research on adult neurogenesis into a mainstream pursuit.” However, the neurons being continually born throughout adulthood are only in certain areas of the brain, not where dopaminergic neurons hang out.
So, what about transplanting dopaminergic neurons into the brain to take the place of all those dead soldiers? Turns out, this has been successfully done by Dr. Curt Freed out of the University of Colorado. Here is a description from his bio:
“In 1988, my neurosurgical colleague, Robert Breeze, MD, and I performed the first transplant of human fetal dopamine cells into a Parkinson patient in the United States. Since that time, we have performed implants on more than 60 Parkinson patients. With support from the National Institutes of Health, we have conducted a double-blind, placebo surgery controlled clinical trial of the transplant method. It was the first placebo controlled trial ever done in the field of Neurosurgery. Results showed that transplants could survive without the need for immunosuppression and could improve objective signs of Parkinson’s disease. That research was published in the New England Journal of Medicine in 2001.
To extend transplantation to more patients, we are developing methods to convert human embryonic stem cells to dopamine neurons. These techniques should make it possible to produce unlimited quantities of dopamine cells for transplant. With these human cells, we have successfully treated animals with a condition similar to Parkinson’s disease. We expect that this stem cell strategy will be available to Parkinson patients in the coming years. “
If you’re noting this all happened a long time ago (2001) and wondering why this hasn’t yet “come to market”, Dr. Freed provided more background when he spoke at the Northwest Parkinson Foundation HOPE conference in November, 2012. First of all, the use of human fetal stem cells meant the stem cells available were drastically limited. This limitation has recently been lifted by Nobel-Prize winning work enabling stem cells to be created from adult skin cells. Another factor is that NIH (National Institute of Health) funding has been flat since 2004, per Dr. Freed. As Congress stumbles towards a balanced budget, it’s likely that something “extra” like NIH could be cut even more. And finally, as with all medical trials, finding volunteers is always a time-consuming challenge. Facilitating recruitment for medical trials has been the particular mission of the Michael J. Fox Foundation.