Scientists uncover nuclear process in the brain that may affect disease

NIH | OCTOBER 1, 2015

Every brain cell has a nucleus, or a central command station. Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.

Some neurological disorders are associated with higher than normal brain levels of the growth factor TGF-beta, including Alzheimer's disease and brain injury. After brain injury, astrocytes produce greater amounts of p75 neurotrophin receptor (p75NTR), a protein that helps cells detect growth factors. The cells also react to TGF-beta by changing their shapes and secreting proteins that alter neuronal activity.

Scientists showed that eliminating the p75NTR gene prevented hydrocephalus in mice genetically engineered to have astrocytes that produce higher levels of TGF-beta.

Hydrocephalus is a disorder that fills the brain with excess cerebrospinal fluid. Eliminating the p75NTR gene also prevented astrocytes in the brains of the mice from forming scars after injuries and restored gamma oscillations, which are patterns of neuronal activity associated with learning and memory.

The cell nucleus is a ball of chromosomes wrapped in a protective fatty membrane. The researchers discovered that treating astrocytes with TGF-beta freed a small piece of the p75NTR protein to bind to nucleoporins, a group of proteins that regulates the passage of molecules in and out of the nucleus. Their results suggest that binding enhances the flow of certain critical molecules into the nucleus and enables astrocytes to enter a reactive state.

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