Lifeboat Foundation

Male and female mice use different brain circuits to process threats, revealing sex-specific neural pathways despite similar behaviors. These findings suggest the need for sex-inclusive neuroscience research to improve understanding and treatments.

With their slender tails, human sperm propel themselves through viscous fluids, seemingly in defiance of Newton’s third law of motion, according to a recent study that characterizes the motion of these sex cells and single-celled algae.

Kenta Ishimoto, a mathematical scientist at Kyoto University, and colleagues investigated these non-reciprocal interactions in sperm and other microscopic biological swimmers, to figure out how they slither through substances that should, in theory, resist their movement.

When Newton conceived his now-famed laws of motion in 1686, he sought to explain the relationship between a physical object and the forces acting upon it with a few neat principles that, it turns out, don’t necessarily apply to microscopic cells wriggling through sticky fluids.

At the recent annual International AIDS Conference, a startling presentation about the newest wonder drug in HIV prevention brought a raucous standing ovation.

But some of us in the public health community are now starting to wonder what all the cheering was about. Although the scientific results were impeccable, the process for translating those results into action for young women in Africa has been left to our imaginations. And if history is any guide, this could be a nightmare.

When the results first came out, Gilead, the manufacturer of lenacapavir, stated it was too early to discuss licensing and offering vague plans about its production and availability in Africa. Just recently, a second study among men who have sex with men and predominantly conducted in the Northern Hemisphere showed similarly promising results. While Gilead now says they have sufficient data to move ahead with licensing and manufacturing worldwide, they have offered no timeline to do so. Urgency to report trial results has not been mirrored by the urgency to provide access. Unanswered questions remain about why another study was needed to move ahead with approvals for use in African women, and if and when lenacapavir will be made available at an affordable price in the African region.

Continue reading “Tested in Africa, used in America” »

Researchers have uncovered how hormones profoundly affect our immune systems, explaining why men and women are affected by diseases differently.

Scientists from the Karolinska Institutet in Sweden and Imperial College London have shown for the first time which aspects of our immune systems are regulated by sex hormones, and the impacts this has on disease risk and health outcomes in males and females.

It is well established that diseases can affect men and women differently, due to subtle differences in our immune systems. For example, the immune condition systemic lupus erythematosus (SLE) is nine-times more likely to affect women, or with COVID-19, males are known to have a greater risk of acute first-time infections, while females have a greater risk of long-COVID.

Muir et al. explore threat discrimination in male and female mice and find that, despite similar behavioral acquisition, there are surprising sex differences in the neural encoding that drives suppression of reward seeking under threat.

A new study has uncovered significant differences in how male and female mice process threats, even as they exhibit similar behavioural responses. The discovery suggests that including both male and female subjects in neuroscience research will lead to more accurate conclusions and ultimately better health outcomes. Understanding the influence of sex on brain function can help explain why males and females develop certain psychiatric disorders at different rates or with different symptoms, the researchers said. ‘Unless we thoughtfully and rigorously integrate sex into biomedical research, a huge amount of the population may be underserved by scientific knowledge,’ said McGill University Associate Professor and Canada Research Chair in Behavioural Neurogenomics Rosemary Bagot, who led the study. ‘Our work shows that sex is an important variable to consider, even if initial observations don’t necessarily show clear sex differences,” said Bagot. “If males and females are using different brain circuits to solve similar problems, they may be differently vulnerable to stress and respond differently to treatments.’ How brain circuits process threats and cues The study focused on two related brain circuits and their roles in processing information about threats and the cues that predict them. The researchers trained mice to recognize a sound that signalled a threat and another sound that meant safety. By observing brain activity, the team saw how communication between different brain areas processed these signals. Then, they temporarily turned off each brain connection to see how it affected the mice’s reactions, helping them understand how the brain handles threats. ‘We found that even though male and female mice respond similarly to threats, the brain circuits underlying these responses are not the same,’ Bagot said. For female mice, a connection between two specific brain areas (the medial prefrontal cortex and the nucleus accumbens) played a key role. The study found that in male mice, a different connection (between the ventral hippocampus and the nucleus accumbens) was more important for handling the same situation. It was previously assumed that similar behavior meant similar brain function. Now, the researchers are exploring how sex impacts brain circuits in processing threats, focusing on the role of sex hormones and different learning strategies. This research is supported by funding from CIHR. About the study Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior by Jessie Muir, Eshaan Iyer et al., was published in Nature Neuroscience.

Aging is known to have profound effects on the human brain, prompting changes in the composition of cells and the expression of genes, while also altering aspects of the interaction between genes and environmental factors. While past neuroscience studies have pinpointed many of the molecular changes associated with aging, the age-related genetic factors influencing specific neuron populations remains poorly understood.

Recent studies on flies, mice, primates and human brain tissue utilizing single-cell or single-nucleus RNA-sequencing and genetic experimental techniques shed new light on these cell-type-specific changes. For instance, they unveiled the effects of aging on glial cells in the mouse and human brain, associations between cell-specific changes and modified chromatin proteins, and the influence of DNA methylation in the aging of various tissues.

Researchers at University of California (UC) San Diego and Salk Institute recently carried out a study aimed at better understanding how both age and sex impact human cortical neurons at a single-cell level. Their findings, published in Neuron, offer new insights into how aging affects cell composition, gene expression and DNA methylation across human brain cell types, while also uncovering differences between gene expression and DNA methylation in females and males.

During her PhD research at Johns Hopkins University, Klein learned how sex hormones can influence the brain and behavior.

A handful of immunologists are pushing the field to take attributes such as sex chromosomes, sex hormones, and reproductive tissues into account.

Researchers have discovered sex-specific differences in the nerve cells that generate pain, paving the way for personalized pain management treatments based on patient sex.

Research indicates that men and women experience pain differently, but the reasons behind this have remained unclear. A new study from the University of Arizona Health Sciences, published in the journal BRAIN, has now identified functional sex differences in nociceptors, the specialized nerve cells that produce pain.

The findings support the implementation of a precision medicine-based approach that considers patient sex as fundamental to the choice of treatment for managing pain.