The current study, led by Teresa Milner, Ph.D., used animal tissue and evaluated changes in neuronal structure with electron microscopy techniques that could visualize changes in protein distribution inside individual dendrites. A different study, conducted independently with cells in fluid culture, obtained similar findings and was published in the same journal issue.

"We found a novel way in which estrogen affects neuronal structural remodeling in the hippocampus," said Bruce S. McEwen, Ph.D., a coauthor of the Milner study. "It shows us that estrogen plays an unsuspected role in primary biological processes involved in strengthening normal learning and memory function."

Findings from several previous studies have been mixed about whether estrogen replacement therapy supports brain function in postmenopausal women. McEwen said that the new study suggests some form of postmenopausal estrogen replacement may indeed be both helpful and neuroprotective.

"Even without estrogen, there are still plenty of synaptic connections in the hippocampus," McEwen noted. "The study suggests that without estrogen, the connections that are there don't work as efficiently in storing and recalling certain types of memories, such as word lists, or remembering where something is in space. The hope is that an estrogen mimic could be developed that protects women not just against memory loss, but Alzheimer's disease, the consequences of stroke and other brain disorders."

In earlier research with rodents, Milner and her group had demonstrated that neurons in the CA1 region of the hippocampus have estrogen receptors on their dendritic spines. When the spines are stimulated, they grow and enhance connections with adjacent neurons, a process called dendritic maturation.

The researchers believe that plasticity, the constant structural reshaping of synapses through formation of new dendritic spines, encodes processes necessary to promote learning and memory. These spines are diminished in the aged brain and are atrophied in Alzheimer's disease. Furthermore, McEwen believes that the formation of new spines may be a major way by which the brain protects itself from damage such as trauma and stroke. Plasticity also allows the brain to relearn skills that may have been lost to injury -- such as by stroke -- by rewiring important functions via alternate nervous system pathways.

Previous studies in mammals by several research groups have shown that low estrogen levels reduce animals' performance on learning and memory tests and estrogen treatment reverses this negative effect in the hippocampus. Human studies have shown that the ability of women to remember word lists and other experimental tasks varies during a normal menstrual cycle, which is characterized by variance in estrogen levels.

The current study is the first to shed light on the precise molecular pathway by which estrogen increases the plasticity of dendritic spines. Through the use of electron microscopy that could distinguish differences in protein level within a dendrite, Milner and her group were able to link the stimulation of estrogen receptors on dendritic spines to synthesis of new proteins within spines that result in dendritic maturation.

The authors hope that an understanding of the pathways through which estrogen stimulates neuronal plasticity will enable researchers to develop selective agents that affect the pathways in a manner similar to that of estrogen.