UW mice mousing for Alzheimer's breakthrough

It is a mystery why those who suffer from the degenerative disease known as Alzheimer's lose their memory. However, a recent discovery made by a professor at the UW's School of Medicine may shed some light as to why this occurs.

Dr. Robert Steiner, a neuroendocrinologist, created transgenic mice to aid him in a study of the relationship between neurotransmitters and the reproductive system. A transgenic mouse has one or very few specific genetic traits modified by the researcher. In this case, Steiner deliberately gave the mice an overabundance of the neurotransmitter Galanin.

Galanin has several functions in the brain, from regulating food intake to playing a role in learning and memory. Neurons, the basic nerve cells in the brain, produce Galanin; when a nerve is damaged, extra Galanin is generated to repair it. However, this normally benign chemical has also been found in large quantities in areas of the brain that have been affected with Alzheimer's.

Steiner collaborated with Dr. Jacqueline Crawley of the National Institutes of Mental Health and a Galanin researcher. Together, they decided to use Steiner's mouse model find a link between excess Galanin production and Alzheimer's disease.

Along with various colleagues, Steiner altered his study of the transgenic mice and found an interesting link between Galanin and Alzheimer's:

• The mice appeared to have normal motor and sensory abilities, yet they had difficulties performing tasks that required the use of memory.

• Specifically, olfactory (smell) and spatial memory were the most affected by the excessive Galanin.

• Since the olfactory and spatial memory functions rely on different parts of the brain, Steiner concluded the symptoms of the mice mimicked the wide-ranged memory loss that afflicts humans with Alzheimer's.

"This could be a sad irony," said Steiner. "As the brain attempts to rescue itself with Galanin and the disease progresses, the overexpression of Galanin may become its own problem."

Steiner's discovery is not, however, concrete evidence that excessive Galanin production is the main cause of Alzheimer's disease. Alzheimer's researchers suspect a combination of Galanin excess, along with the loss of key brain cells, leads to the gradual decline in memory.

Since Steiner's transgenic mice can now be used as a model to test possible treatments for Alzheimer's, researchers are deciding whether to test Galanin-blocking drugs on the mice. Dr. Elliot J. Mufson, one of Steiner's colleagues who participated in the study, said using the mice to find a single drug to prevent Alzheimer's.

"Because Alzheimer's is so complicated, it may be that someday people will have to take a whole cocktail of drugs," said Mufson.