Estrogen Wires the Brain

Estrogen is famous for its role in regulating sexual development and infamous for its role in breast cancer. Now, it appears that the hormone also encourages neurons to hook up with their neighbors in a part of the adult rat brain called the hippocampus, known primarily as a site for memory and learning. The finding may ultimately help explain these functions in humans, and it could clarify the role of estrogen in some kinds of epilepsy.

The roots of memory, learning, and neurological problems such as epilepsy lie in the chatter of neurons. After a neuron picks up a signal, the message travels to the body of the neuron via a tendril-like projection known as a spine. Once the signal is processed, it may be sent down a longer projection to spines on a neighboring neuron. Several years ago, neurobiologist Catherine Woolley of Northwestern University and her colleagues showed that estrogen increases the number of spines on specific cells in the hippocampus and the connections between them. But did these new spines merely strengthen existing communication channels or form new ones?

To answer this question, Woolley's team members first removed the ovaries from rats, then treated half the animals with estrogen. After 2 to 3 days, they removed the hippocampus, sliced it up, and biochemically labeled individual neurons in each section. They then tracked whether and how the spines of the stained neurons connected with other neurons.

Practically all of the spines in estrogen-treated rats were connected to more than two other neurons, the researchers report in the 20 February online edition of the Proceedings of the National Academy of Sciences. Neural spines in the control rats, in contrast, tended to patch into only one other neuron. This means that estrogen may be adding new connections in the brain, Woolley says. This process could be "vital to understanding how the whole [neural] circuit works," she says, even if the exact mechanism is unknown.

The finding "reinforces the idea that the adult brain remains remarkably plastic," says Marc Breedlove, a psychologist at the University of California, Berkeley. Woolley adds that the finding may explain why high estrogen levels correlate with frequency of seizures in many women with temporal lobe epilepsy. The disorder, in which collections of neurons fire in synchrony, seems to originate in the hippocampus. "If one hippocampal cell previously spoke to seven cells," she says, "and estrogen causes it to talk to three more, this change could promote seizure activity."

Related sites

Novartis Foundation-sponsored interview on neural and cognitive effects of estrogen

Comprehensive Epilepsy Management Center at Albert Einstein College of Medicine