Motherhood alters brain and response to hormone therapy

Motherhood alters the brain permanently in ways significant for hormone therapy, says a new study explaining why the effects of therapy in treating cognitive decline is so varied.

Hormone therapy (HT) used to alleviate menopause symptoms in women could have a beneficial or deleterious effect depending on the form of estrogen used and motherhood status, says research by Liisa Galea, at the University of British Columbia.

Estradiol, the predominant form of estrogens in young women, has beneficial effects, while estrone, the form of estrogen in older women, impairs the brain further in treatment.

Besides, estrone-based HT impaired learning in middle-aged rats that were mothers, while it improved learning in rats that were not.

Galea's results were presented at the ninth Annual Canadian Neuroscience Meeting, on 25 May in Vancouver British Columbia.

"Our most recent research shows that previous motherhood alters cognition and neuroplasticity in response to hormone therapy, demonstrating that motherhood permanently alters the brain," says Liisa Galea.

Galea looked at the form of estrogens used in HT. There are three forms of estrogens: estradiol, estrone and estriol.

A systematic review of the published scientific literature indicates that estradiol-based HT may have more beneficial effects.

Galea studied how two forms of estrogens affect neuroplasticity. Her studies focused on the hippocampus, which has important roles in memory and spatial ability, such as navigational skills.

While both forms of estrogens increased the production of new cells in a part of the hippocampus called the dentate gyrus in young females, the survival of these neurons was aided by only chronic estradiol, which also increased the expression of zif268, a protein involved in neuroplasticity.

Chronic estradiol also improved performance of young female rats in a behavioural test called the water maze where they have to rely on cues located around them to swim ashore.

Changes in hippocampus

Working on her previous research that had shown that motherhood causes changes in the architecture of connections in the hippocampus, Galea's team investigated the varying effects of different forms of estrogens on rats that had experienced motherhood once (primiparous rats) and on those who had not (nulliparous rats).

They found that estrone-based HT improved learning in middle-aged nulliparous rats, but impaired learning in primiparous rats of the same age. These primiparous rats also showed a reduction in neurogenesis and zif268, a protein involved in neuroplasticity in the hippocampus.

"Hormones have a profound impact on our mind. Pregnancy and motherhood are life-changing events resulting in marked alterations in the psychology and physiology of a woman. Our results argue that these factors should be taken into account when treating brain disorders in women," concludes Liisa Galea.