Frontier: Environment influences gene expression

by Tom Valeo

January, 2009

Certain genes apparently predispose some people to mental illness, as family inheritance patterns suggest, but new research demonstrates that environmental influences can alter the way genes express themselves, thereby influencing brain activity.

This process, known as epigenetics, involves chemical “marks” on the DNA that either stifle or enhance the activity of genes. Epigenetic changes in the brain can affect development, memory and fear, and contribute to mental disorders, according to research presented at the Society for Neuroscience meeting.

Epigenetic changes result, in part, from changes in methylation, or the presence of methyl group molecules in DNA. Methyl groups keep the DNA in a tight bundle. Altering the methylation of the gene for BDNF, a protein crucial for learning, can block the formation of a normal fear response, said

Farah Lubin, a neurobiologist at the University of Alabama. Abnormal regulation of this gene has been implicated in the development of mental illness.

Lubin and her colleagues induced fear in a rat by inflicting a mild foot shock whenever the animal was placed in a particular training chamber. However, after receiving zebularine, a cancer drug that affects the methylation of DNA, the rat failed to produce sufficient BDNF in its hippocampus to consolidate the experience into a long-term memory and therefore did not develop the normal fear response.

Because abnormal BDNF gene expression is suspected in psychiatric disorders including schizophrenia, depression and bipolar disorder, manipulating the epigenetic process may lead to new therapies, Lubin said.

Tania Roth, also a neurobiologist at the University of Alabama, believes epigenetic influences help explain the long-lasting effects of abuse early in life. When she and her colleagues exposed newborn rats for 30 minutes a day to a stressed adult caregiver who handled them roughly, the newborn rats developed changes in BDNF expression in the amygdala, the brain region responsible for emotional processing.

“We find early experiences produce changes in BDNF expression that persist into adulthood,” she said. “This is due to lasting changes in the methylation of the DNA.”