Lightning in a bottle

Persuading a dead neuron to fire is a key step in conquering diseases that ravage the human mind
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First Published: Thu, Oct 04 2012. 06 23 PM IST
A still from the movie ‘Deep Blue Sea’.
A still from the movie ‘Deep Blue Sea’.
“And what you’re looking for here is lightning in a bottle.”
“Protein complex is interacting with the neurons.”
“Neurons are becoming hyperosmotic.”
“Membrane integrity’s improving.”
“They’re firing! They’re firing!”
The dialogue is campy, and the science is riddled with absurdities. But the scriptwriter of a 1999 movie Deep Blue Sea was remarkably prescient in discerning a scientific frontier: To reactivate or regenerate dead human neurons and conquer diseases that ravage the human brain.
The folks at Warner Brothers inadvertently re-ran the movie—in which 3,600kg mako sharks conspire to destroy an undersea research facility after they are made intelligent by scientists hurrying to find an Alzheimer’s cure—on satellite television during a week when at least three diverse, but significant advances were announced in efforts to reverse brain damage.
The first advance, announced in The FASEB (Federation of American Societies for Experimental Biology) Journal, centred on, not a shark, but a camel. A team of French and US researchers described a new type of antibody discovered in camelids (that means camels, llamas and alpacas). The serum apparently can, without assistance from drugs, seep across what is known as the blood-brain barrier and reach specific brain cells, in this case star-shaped cells called astrocytes, whose function is to supply neurons with nutrients and serve as scaffolding to hold them in place.
Think of astrocytes as being part of the neuron support team. There is growing evidence that astrocytes can influence the construction of neurons and attract other cells to repair neuronal damage. Neurons, some 100 billion of them, are the building blocks of the brain and the nervous systems. They relay messages that allow us to feel emotion, do things and be who we are or think we are.
The second advance, announced in the journal Cell Stem Cell by a team of German scientists, reveals how human neurons can be created from other brain cells called pericytes, which, apart from helping heal injuries in other parts of the body, appear to work with astrocytes to keep the blood-brain barrier intact.
The blood-brain barrier separates the bloodstream from brain tissue and regulates the flow of nutrients, proteins and chemicals between them. The barrier is especially made to keep out bacteria, but some manage to cross over, including those responsible for tumours, brain traumas and multiple sclerosis. It is at this junction that scientists attempt many interventions, as the German team did in reprogramming pericytes to become neurons.
“The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain,” said Benedikt Berninger, a neurobiologist, quoted in a press release.
The third advance, described in two papers in the Proceedings of the National Academy of Sciences, identifies a family of chemical compounds that protect neurons from the ravages of degenerative diseases such as Alzheimer’s and Parkinson’s.
The advances come thick and fast at a time when century old wisdom—that human neurons cannot grow after maturity —is being discarded. There is sustained research, and there is serendipity, all combining to advance medical research towards the holy grail of regenerating neurons and reversing brain damage.
In July, for instance, Canadian medical researchers announced, also in Cell Stem Cell, that a drug called metformin, commonly used to control Type 2 diabetes, helps kick-start stem cells into becoming brain cells, including neurons.
Stem cells are precursor cells that can become other cells and so repair, as the hope goes, injuries to the body. They can either be harvested from the body or artificially grown to form specific tissues. Pericytes, too, are a type of stem cell.
In the metformin study, the drug was infused into stem cells from mice and the human brain. Both experiments led to the creation of new brain cells. Rats given daily doses of the drug for a couple of weeks even appeared to become smarter.
For all the excitement, much of the research in neuron and brain repair has been conducted in petri dishes or, at most, in mice and worms. Some worms are particularly attractive to science because they can regenerate not just neurons but their entire bodies from tissue fragments.
In the case of metformin, there simply may not be enough brain stem cells to produce new neurons as people age and stem cells diminish. As for Alzheimer’s, there is, yet, no cure in sight, although it is the disease most often spoken about as a target if science can grow new neurons or persuade dead neurons to fire again. Research is generating many sparks but no lightning in a bottle.
“I’ll be damned,” says the millionaire financier to a scientist after the neuron-firing scene in Deep Blue Sea.
The scientist replies: “No sir, for six seconds, you saw what it’s like not to be damned.”
If only.
Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology.
To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail
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First Published: Thu, Oct 04 2012. 06 23 PM IST
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