Dementia
Sleeping on it
Feb 2nd 2006
From The Economist print edition
Similarities between dementia and hibernation suggest a treatment
WHEN an Arctic ground squirrel hibernates, its body temperature drops below the freezing point of water and the blood-flow through its brain slows to a trickle. Though the squirrel's brain survives, it loses many of the nerve-cell connections that govern how it operates. The brain regenerates itself soon after the animal emerges from its long sleep. Exactly how is a matter of intense research but one group of scientists thinks that part of the explanation lies with a protein associated with Alzheimer's disease. And that raises the hope that the ravages wrought on the human mind by Alzheimer's disease could be as reversible as the winter freeze.
Arctic ground squirrels hibernate for up to seven months of the year, sinking into a torpor from which they periodically rewarm their bodies to 37°C before re-entering the supercooled state. Research has shown that during hibernation these animals lose memories they laid down beforehand and also their ability to form new ones. This loss must be temporary, however, or the animal would become more amnesic with each hibernation.
The brain stores information in neuronal networks. The chemical connections between neurons, called synapses, are thought to be critical to the formation of those networks and hence the laying down of memories. In 2003 a group led by Thomas Arendt of the University of Leipzig in Germany showed that the number of synapses in the hippocampus, a brain structure crucial for learning and memory, falls during hibernation. This is partly because hippocampal neurons lose many of their branching projections, or dendrites, and so provide less opportunity for forming synapses with neighbouring neurons.
All that changes within two or three hours of an animal emerging from hibernation, when a wave of new growth ensures that the number of synapses in the hippocampus soars beyond even pre-hibernation levels. The next 20 hours see a pruning back of those connections, rather as in the very young human brain. Just as in that developmental process, the new synapses seem to enhance memory only once the pruning has taken place.
Nobody knows what triggers these dramatic morphological changes in the hippocampus during and after hibernation. But Dr Arendt's group has made the startling discovery that hibernating brains accumulate a protein called hyperphosphorylated tau. This protein is known also to accumulate in the neurons that degenerate in the brains of people with Alzheimer's disease. Notably, though by no means exclusively, it accumulates in the hippocampal neurons, where it is associated with the formation of lesions.
There are several competing theories about what causes Alzheimer's disease. One possibility is that the tau protein causes the lesions in the brain. Another is that something else causes the lesions, and the tau protein is the brain's defence against that attack. Thus, it is possible that the tau protein might not be the problem, but rather a symptom of the problem.
During hibernation, the levels of tau protein in a squirrel's hippocampal cells are directly correlated with the loss of synapses—but not with the appearance of lesions. On emerging from hibernation, the squirrel eliminates the tau protein from its brain. This has led Dr Arendt to suggest that rather than being a part of a disease process, the formation of the tau protein could be a mechanism by which the brain protects itself. He argues that the brain is armed with mechanisms for clearing the tau protein and that the reason it doesn't in people with Alzheimer's disease is because the protein is protecting the neurons.
His stance is contentious. “As the field stands, viewing pathology as anything other than pathogenic is controversial. Saying it is protective is heretical,” says Mark Smith of Case Western Reserve University in Cleveland, Ohio. He has conducted studies on living neurons which suggest that the tau protein is produced in response to oxidative stress, thus lending support to the protective hypothesis.
Dr Arendt's group is now engaged in discovering exactly how the tau protein can be cleared from the brain. Help for Alzheimer's patients remains uncertain and a very long way off, but spring seems to have come a bit closer.
