Northwestern Medicine researchers have discovered how oestrogen physically works in brain cells to boost mental performance.

Oestrogen is an elixir for the brain, sharpening mental performance in humans and animals and showing promise as a treatment for disorders of the brain such as Alzheimer’s disease and schizophrenia. Now, the team has found how benefits of oestrogen can be reaped without risks of cancer, heart disease and stroke. Using a special compound, they flipped a switch that mimics the effect of oestrogen on cortical brain cells.

When scientists flipped the switch, they witnessed a dramatic increase in the number of connections between brains cells, or neurons. Those connections, called dendritic spines, are tiny bridges that enable the brain cells to talk to each other. “We created more sites that could allow for more communication between the cells. We are building more bridges so more information can go from one cell to another,” said Deepak Srivastava.

“A major theory is if you increase the number of spines, it could be a way to treat these significant mental illnesses,” he added.

Northwestern scientists also identified aromatase, a critical protein needed to produce oestrogen, to be in precisely the right spot in the brain cell to make more dendritic spines. The team now wants to further identify the key molecules involved in the dendritic spine production and target them in the same way as the oestrogen receptor in order to ultimately be able to treat schizophrenia and other mental disorders.

"As we understand the effects of these specific oestrogen receptor beta compounds in preclinical models, we are discovering effects on specific neuronal functions, which could be relevant for the treatment of cognitive disorders, depression and schizophrenia,” said Nick Brandon, head of psychiatry at Pfizer Inc., whose group collaborated with the Penzes lab for this work.

The findings will be presented Nov. 17 at Neuroscience 2010 in San Diego.

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