The brains of hibernating animals undergo wide temperature variations and periods of energy deficiency. Neurobiologist Ate Boerema has shown that changes occurring in the brains of hibernating Syrian hamsters as a result of energy deficiency are very similar to the brain damage in Alzheimer’s sufferers. The Syrian hamster is therefore a reliable model for studying brain changes relating to Alzheimer’s disease. Boerema will be awarded a PhD by the University of Groningen on 16 March 2012.
Hibernation is a way to survive harsh conditions. In order to conserve energy, hibernators enter a state of torpor – a period during which they effectively shut down their metabolism. The body cools, sometimes to temperatures just above the ambient temperature.
By no means all hibernating animals remain in a state of torpor throughout the winter. For short periods their body rewarms, probably for the purpose of brain ‘maintenance’. Boerema studied the brain of an ‘interval sleeper’, the Syrian hamster (golden hamster). The brain changes that Boerema observed in this hamster during hibernation are similar to changes in the brain of Alzheimer’s sufferers: the tau protein undergoes phosphorylation (the addition of a phosphate group).
Tau proteins are found in healthy nerve cells. They reinforce the skeleton of the cell, in the same way as the rungs of a ladder, and enable the transport of nutrients in the cell. When phosphate groups accumulate on the tau protein (phosphorylation), they impair the function of the protein and eventually even cause it to curl up. The result is disastrous: the cell dies. This change also takes place in people with Alzheimer’s disease,’ explains Boerema. ‘the curled-up tau proteins form the tangles in the brain that are characteristic of Alzheimer’s.’
In hibernating Syrian hamsters, however, the results are not disastrous. Before irreversible brain damage can occur, they emerge from the torpor for brief periods and the brain rewarms. Boerema: ‘The brain rewarms first, then the rest of the body. The phosphate groups disappear from the tau protein at a temperature of approximately 28°C – the same temperature at which they began to accumulate.’ The hamsters do not have Alzheimer's disease, says Boerema: 'After a period of hibernation, the animals can remember precisely where they have stored food.'
As to why phosphorylation occurs precisely at 28°C, Boerema can only speculate: ‘It is precisely the point at which REM sleep no longer registers on the EEG of hibernators whose body temperature is cooling. At lower temperatures there is almost no visible brain activity on an EEG. We suggest that the phosphate groups on the tau protein are taking the place of sugars. thereby limiting the cell’s ability to expend energy. The phosphorylation ‘sets’ the brain structure, as it were, and helps to limit energy use by the nerve cells as the body cools, so that the cells are protected from damage.’
Boerema’s findings do not mean that the tau-protein hyperphosphorylation and the resulting tangles in Alzheimer’s sufferers are irreversible. Boerema: ‘There are differences between the brain of an Alzheimer's sufferer and that of a hibernating animal. In the case of Alzheimer’s, there are many factors that influence the disease process, including a problem with cellular energy in the brain that causes the damage. The underlying problems need to be solved first. This research is important because we have found a natural animal model for studying changes in the brain – changes that we also observe in people with Alzheimer’s disease.’
Ate Boerma (Groningen, 1979) studied biology at the University of Groningen. After graduating, he also carried out his PhD research at the University of Groningen, in the departments of Chronobiology and Molecular Biology. Boerema will be awarded a PhD in mathematics and natural sciences. His research was supervised by Prof. Serge Daan and Prof. Eddy van der Zee. His thesis is entitled: The brain at low temperature: neuronal and behavioural dynamics in mammalian hibernation and torpor.
More information: Ate Boerema, e-mail: a.s.boerema rug.nl, tel. +31 (0)363 7848; +31 (0)361 5779
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