Why ‘mumnesia’ strikes: Mouse study offers clues to pregnancy forgetfulness

HOUSTON – It is sometimes called “mumnesia”, “mummy brain”, “pregnancy brain” or “baby brain” – the forgetfulness, mental fogginess and cognitive changes that many women may experience during pregnancy.

For instance, a woman might walk into the kitchen and forget why she did so, or perhaps misplace her car keys in the bathroom.

Scientists know it is a real biological phenomenon and have found a possible explanation, identifying a specific brain circuit that becomes disrupted under the sustained high levels of oestrogen that accompany pregnancy.

They conducted experiments using laboratory mice designed to mimic the sustained elevated oestrogen experienced during pregnancy, finding that this led to temporary memory impairment in the animals without mood changes.

Underlying this in the mice, they found, was how the high oestrogen affected a neuronal pathway between two brain structures – the hypothalamus, which acts as a control centre and integrative hub; and the hippocampus, which is central to memory formation.

High oestrogen increased the activity of hypothalamus neurons, which in turn suppressed activity in the hippocampus and impaired memory, they found.

“Mumnesia” becomes most evident in late pregnancy and may continue into the post-partum period, but usually dissipates after childbirth.

Short- and long-term memory can be affected, including spatial, social and verbal memory such as having difficulty remembering names or words, or struggling to recall familiar information.

“It is not serious or medically disabling, although it does affect daily functioning and confidence,” said Zheng Sun, a professor of medicine at Baylor College of Medicine specialising in endocrinology and molecular biology and one of the leaders of the study published in the journal Science Bulletin.

“Typical examples include forgetting why one entered a room, misplacing an item, losing the thread of a conversation or needing reminders for appointments. It is widespread. About 80% of pregnant women notice those changes, but that figure largely reflects self-report and subjective experience rather than objective testing,” Sun added.

The findings suggest that the phenomenon does not represent a general decline in cognitive ability.

“The important point is that pregnancy does not simply make someone ‘less intelligent’. The effects appear to be more subtle and specific to certain cognitive tasks,” said Yanlin He, director of the Brain Glycemic and Metabolism Control Laboratory at Louisiana State University’s Pennington Biomedical Research Center and another of the study leaders.

Mouse experiments

The mouse experiments shed light on what is happening in the brain.

Oestrogen is a hormone that governs a woman’s pregnancy, menstrual cycle and puberty, spurring physical changes that help the body support the foetus, foster foetal development and prepare for childbirth. Its levels increase during pregnancy, peaking in the third trimester.

The researchers found that a protein called “oestrogen receptor alpha” transmits oestrogen’s signals into cells in the hypothalamus.

This region has abundant brain cells called GABAergic neurons that typically transmit calming signals to other parts of the brain. The study showed that high oestrogen levels over-activate the inhibitory signals by these neurons in the mice, and this directly affected the hippocampus.

The researchers performed memory tests, including object and location recognition, finding impairment in mice given high oestrogen levels compared with those that were not.

When the researchers experimentally turned off the hypothalamus-to-hippocampus neuronal pathway, the mice no longer experienced oestrogen-induced memory problems.

But experimentally activating the same pathway impaired memory in the mice, even without higher amounts of oestrogen present.

“When we genetically removed oestrogen receptors from these hypothalamic neurons, oestrogen- and pregnancy-induced memory problems in mice were also reversed. We suspect that a similar circuit may play a similar role in humans, although you cannot do this type of invasive study directly in humans,” Sun said.

The researchers complemented the mouse experiments with a study assessing memory performance in 70 women, including some across different stages of pregnancy and some who were not pregnant, using tests of long-term, short-term and working memory. These tests revealed memory impairments that manifested during late pregnancy, correlating with high circulating oestrogen levels.

“Importantly, higher circulating oestrogen levels were associated with poorer performance on several memory-related measures even after accounting for other potential contributing factors. This provides human evidence consistent with the mechanism we identified in mice,” He said.

“However, we should emphasise that we did not directly manipulate or measure this specific neural circuit in pregnant women,” He added. “Therefore, the human findings support the hypothesis, but do not establish the same level of causality as the mouse experiments.” REUTERS