The Estrogen Connection

1012 neuro4Aging-related diseases are not the only causes of learning and memory problems, as anyone who has suffered from depression can tell you. Women are diagnosed with depression twice as often as men and tend to be more susceptible to depression during hormonal changes like puberty, postpartum, and menopause, says Lori McMahon, Ph.D., Jarman F. Lowder Professor of Neuroscience at UAB, director of the UAB Comprehensive Neuroscience Center, and associate director of the Center for Aging. But “estrogen doesn’t cause the depression—it’s due to the misregulation of hormones,” she explains.

Moreover, McMahon’s research in animal models indicates that estrogen can alleviate some of the cognitive problems associated with depression. By looking at neurons in the hippocampus directly, McMahon’s lab found that estrogen has a neuroplastic effect, increasing the number of synapses (sites of neuronal connections).

By looking at neurons in the hippocampus directly, McMahon’s lab found that estrogen has a neuroplastic effect, increasing the number of synapses (sites of neuronal connections).

At first glance, McMahon’s findings appear to contradict the results from the Women’s Health Initiative study, which reported that hormone replacement therapy did not provide any benefits to women experiencing memory problems after menopause. However, McMahon points out that the benefits may have been missed because most of the women went without estrogen for 10–15 years before treatment. In a study published in Proceedings of the National Academy of Sciences in 2010, McMahon found that even very old animals benefitted from estrogen replacement after ovary removal (a mimic of menopause)—but only if the period between removal and the start of estrogen therapy was short. “So, it’s really not chronological age, but the period of hormone deprivation that’s the problem,” she notes. If hormone replacement therapy is started too late, “age-related mechanisms are probably already in motion.”

McMahon’s lab continues to investigate the impact of estrogen loss in aging and the value of estrogen replacement, as well as estrogen’s role in depression. The researchers are particularly interested in NR2B, a subunit of the NMDA glutamate receptor implicated in learning and memory. A new paper by the scientists in the journal Hippocampus shows that estrogen increases NR2B function, which in turn increases novel object recognition. This follows a landmark 2006 finding by the McMahon lab that increased activation of NR2B is also responsible for a rise in synaptic plasticity in the hippocampus, “suggesting that the increase in plasticity underlies increases in learning and memory,” McMahon says.

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