“Momnesia”: why and when memory lapses occur during pregnancy, and how much of a role hormones play

Where have I put my smartphone? Why can’t I follow a conversation? Why do I forget to buy what I need when I’m out shopping? For many pregnant women, especially in the third trimester, there’s a sort of ‘brain fog’ that seems to take over their minds, causing their concentration and memory to wane. Attributing these difficulties solely to the stress of pregnancy and worries is limiting and inaccurate, so much so that various hypotheses have been put forward to explain what is happening. But it now seems that the biological ‘key’ to these mental difficulties has been found, in a process linked to high levels of circulating oestrogen and their impact on a specific brain circuit.

This is the finding of a study published in Science Bulletin, coordinated by scientists at Baylor College of Medicine led by Zheng Sun, Yanlin He, at the Pennington Biomedical Research Centre, and Xinguo Hou, from the Qilu Hospital of Shandong University. Understanding this mechanism could, in future, provide guidance on how to advise women to minimise the cognitive effects of pregnancy or hormonal contraceptives, and pave the way for therapies targeting this specific pathway without interfering with the broader beneficial functions of oestrogen in the body.

The research replicated, in animal models, the high levels of oestrogen in the blood that occur during pregnancy. It was then found that the increase in hormone levels led to a reversible decline in memory, but had no effect on mood or motivation: “This suggests a specific cognitive effect rather than a general change in well-being,” commented Zheng Sun in a statement from Baylor College. But how can this specific effect on memory be explained? This is precisely where the research is groundbreaking. The experts found that the oestrogen receptor alpha – the protein that transmits oestrogen signals to cells – is also present in a specific area of the central nervous system, the lateral hypothalamus. Not only that: this region is rich in so-called GABAergic neurons – cells that normally help to calm and relax other areas of the brain. Unfortunately, it has been observed that high levels of oestrogen ‘switch off’ the signalling system of these neurons, which consequently remain hyperactive. “When we genetically removed the oestrogen receptors from these hypothalamic neurons, the oestrogen-induced and pregnancy-induced memory problems in mice were reversed,” notes Sun.

Analysis of the brain’s anatomy has also revealed something else. The overactive neurons in the hypothalamus project directly into a region of the basal hippocampus that is key to memory formation. Using a technique known as chemogenetics, which turns specific neurons on or off like a switch, experts have shown that silencing this neural pathway from the hypothalamus to the hippocampus protects animals from oestrogen-induced memory problems, whilst artificially activating the same pathway led to impaired memory formation even in the absence of high oestrogen levels.

The research paves the way for understanding the role of oestrogen not only during pregnancy, but also in the post-menopausal phase. What emerges from the study is that perhaps it is not just a question of how many hormones are present, but rather where their action is concentrated. In this respect, the data on women also support the hypothesis that the hormonal circuit identified in mice may underlie the changes in memory that many pregnant women experience. It should be noted, however, that these changes are of limited duration and do not result in a more widespread cognitive decline. “Anyone who works constantly and continuously with pregnant women (or women who have been pregnant) has observed a change in brain function and a reduction in memory – particularly verbal memory – which increases as pregnancy progresses,” explains Giuseppina Picconeri, a gynaecologist and member of the executive board of the Italian Society for Human Reproduction (SIRU). “Obviously, not all women experience this in the same way, but it is certainly more pronounced in those who previously had a formidable memory: There is a significant change in brain neuroplasticity caused not only by increased oestrogen levels but also by rises in progesterone, cortisol and prolactin, as well as reduced sleep – all factors that contribute to altering the balance that existed prior to pregnancy. These are generally temporary changes, but they may take a longer time (in some cases even 2–3 years) to return to the previous state.”