New Scientist visits the lab where brains are sliced in search of the underlying mechanisms of multiple sclerosis and Parkinson's
FOR 12 years, the man in front of me lived with Parkinson's: he had a stammer; he dragged his left foot. At 79, his mental faculties were slowing - but strangely, he didn't have the tremors we normally associate with the disease.
When I say he is in front of me, what I mean to say is that his central nervous system - his brain and spinal column - is laid out before me. I am in a dissection room at the Division of Brain Sciences, Imperial College London.
Neuropathologist Steve Gentleman rotates the man's brain in his gloved hands. With a scalpel he removes the olfactory bulb at the base - sometimes this is smaller in Parkinson's patients, and if it is, they lose their sense of smell. Gentleman points out a slight thickening in the cranial carotid artery, one of the main blood supplies to the brain. "A bit of atherosclerotic build-up, to be expected in a man of this age."
Next, Gentleman locates a couple of bits of tissue under the brain called the mammillary bodies. Using them as a kind of grid reference, he slices the brain in two with what resembles a large bread knife. It opens like a walnut.
"Straight away I can see that the ventricles are very wide," says Gentleman, who has dissected around 1000 brains in his career. "It is consistent with the long progression of the disease."
In the laboratories around us is a small but valuable bank into which about 900 people have made a deposit - one might say the ultimate deposit. The UK Multiple Sclerosis and Parkinson's Tissue Bank contains more than 100,000 individual samples of frozen brain tissue. Some 9000 people have pledged to donate their central nervous systems when they die. The bodies are returned to families for funerals; even an open casket funeral is possible as the brain and spinal cord are removed from the back.
Neuroscientists from around the world apply to the bank for samples, and if successful, they only have to pay for postage. "There's a growing demand, as animal models aren't mirroring the diseases too well," says David Dexter, director of the bank.
Parkinson's disease affects 1 in 1000 people, and in the over-60s, 1 in 100. Multiple sclerosis on the other hand is more likely in younger adults, affecting between 2 and 150 people per 100,000. Both are debilitating neurodegenerative disorders. Drugs can treat the symptoms but in both cases the underlying trigger is unknown. Damage to the insulating cell sheaths in MS cannot be halted or reversed, nor can the death of dopamine-producing cells that are a hallmark of Parkinson's. "The holy grail is to develop neuroprotection," says Dexter.
That is what Dexter is working towards. In his latest publication, he and colleagues examined brain bank tissue and found that the X chromosome is less active in the brains of people with neurological disorders (Frontiers in Neuroscience, doi.org/j8p). Dexter also wants to look at links between epigenetic factors and disease. These chemical modifications of DNA play an important part in controlling how genes are expressed. From donated brain tissue, Dexter has found that part of the epigenetic modification system can inhibit the tightening of the coils of DNA. This seems to protect against Parkinson's.
"As we live longer, more and more of us are going to be affected," Dexter says. "If you look at the 'normal' brains that come into the bank, about 15 per cent actually aren't normal - they've got early stages of a neurodegenerative disease."
Thirty minutes or so later, Gentleman has finished the dissection. Brain tissue is spread out over the table in neat 10 millimetre slices, like some kind of macabre deli counter. "The convolutions of the brain are like fingerprints - no two are the same," he says. "These were individuals. I still see it as a privilege to dissect them. But I have to have a practical disconnect, and I still have no idea how a pile of fat - a lot of lipid membranes - can represent a person."
This article appeared in print under the headline "Your brain in their hands"
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