In recent decades, neuroscience has emerged as one of the most intriguing fields for researchers, focusing their attention on the study of one of the body’s most mysterious organs: the brain. Research has proven that sex differences extend beyond mere reproductive organs and hormones, playing a pivotal role in the prevalence of neurological and psychological diseases and individuals’ responses to treatments. While it was traditionally believed that research favored male models, recent studies have highlighted the importance of including females in biological experiments. In this article, we will review the historical shifts in the scientific research approach regarding the sexes and examine the key developments that led to the recognition of the importance of sex differences in understanding brain mechanisms and the diseases associated with them.
History of Neuroscience Research and the Gender Gap
Neuroscience is considered one of the scientific disciplines that has attracted scientists’ interest for over half a century, with a significant focus on understanding the brain’s mechanism and its associated behaviors. Most studies initially concentrated on male animal and human models, which reinforced the gender gap in this field. The prevailing belief was that data related to males were less complicated and contained less variability than data related to females due to the menstrual cycle of females, which was considered unstable according to previous notions. As research evolved, scientists began to realize that this belief had a detrimental effect on the advancement of knowledge in neuroscience and increased the gender gap in many neurological and psychological disorders.
During the 1990s, scientists provided a series of studies that overturned traditional perceptions of the brain. Studies conducted by the late Bruce McEwen and his team at Rockefeller University demonstrated the effect of estradiol, a female sex hormone, on the density of synapses in the brain’s hippocampal region. These studies confirmed that the hormone’s influence extends beyond reproductive functions. This advancement in research served as a jolt that prompted many researchers to recognize the necessity of including females in studies and clinical trials.
Efforts to Achieve Equality in Scientific Research
The enactment of the Women’s Health Initiative Act in 1993 by the U.S. Congress was a significant step toward addressing the gender gap in scientific research. Although this law resulted in increased representation of women in clinical trials, the impact on basic research was not notable until later. In 2016, the policy of “sex as a biological variable” was launched by the National Institutes of Health (NIH), emphasizing the necessity of including sex in research designs, analyses, and reports in all biomedical studies.
This shift toward including females in research is a key step toward addressing the longstanding biases in this field. However, not all scientists were fully prepared to accept this change. Some expressed concerns that including female models could lead to an increase in variables and complexities in research. Nevertheless, many studies, including research on mice, have proven that the behavioral and neurological outcome gaps between males and females were less than previously thought, reshaping the rules of scientific research.
The Gender Gap in Research Outcomes
Despite progress in integrating females into research, it was found that between 2009 and 2019, the percentage of studies adhering to an ideal design for investigating sex differences remained low. Only 19% of the studies employed an ideal design to discover potential gender differences. Meanwhile, only 5% of the studies included sex as a discovery variable. This indicates that while there has been progress in bridging the gap, there is an urgent need to continue developing research designs to be more inclusive and accurate.
Considered
The differences between genders are essential for understanding psychological and neurological disorders, as the biological differences between males and females represent a significant gap in the prevalence of certain neurological and psychological disorders. For example, it appears that women have different behavioral and experiential responses to stress, pain, and fear compared to men. These differences are of great importance in developing treatments and medications, highlighting the need for precise and comprehensive tests that reflect the biological makeup of both genders.
A Move Towards More Inclusive Neuroscience
It has become clear that studying gender differences is a crucial factor in improving our understanding of mental and neurological disorders. Research should rely on designs that take into account the biological differences between genders, as data reflecting the complexities of both sexes lead to more accurate and realistic results. This represents a qualitative and exciting shift in research, breaking traditional concepts of how the brain works and providing new insights into how males and females respond to different medications and treatments.
Understanding the unique biology of each gender can have a significant impact on how treatments are developed, leading to more effective and personalized medications. In this context, it is essential for researchers to recognize the impact of gender in their studies and strive to develop research that highlights these differences. This will lead to a future of more inclusive neuroscience, benefiting everyone, whether male or female, and enhancing a deep understanding of the human mind and related disorders.
Differences in Responses to Psychological or Nursing Stress
Studies show that the differences in individuals’ responses to psychological or nursing stresses represent a central theme in neurological research. These differences are not limited to psychological factors but also include biological differences between genders. For example, it has been observed that women experience cognitive decline faster than men in cases associated with Alzheimer’s disease, where women represent two-thirds of Alzheimer’s patients. This difference in responses reinforces the importance of studies based on non-human models, as using non-human primate models in research has significant advantages due to their genetic and behavioral similarities with humans.
Agnes Lacruz, a primate scientist at the University of Massachusetts, studies the aging of marmosets, a type of monkey that lives between 10 to 12 years. Through her research, she has discovered that female marmosets show more rapid cognitive decline than males. This illustrates how biological factors can significantly influence the development of psychological and neurological diseases. Therefore, it is essential to conduct comparative studies across species to understand the mechanisms behind these differences.
Exploring Sexual Differences in Cell Lines
Cell lines are a vital tool in studying neurological diseases, and advancements in research through the use of induced pluripotent stem cells (iPSCs) have provided new frameworks for investigating sexual differences. iPSCs, for example, avoid the need for embryos, making them an ethical model for study. By studying these cells, researchers can analyze how genetic differences between genders affect the cells’ responses to diseases like Alzheimer’s.
Scientists like Tracy Young-Bear emphasize the importance of these cells in studying sites associated with Alzheimer’s. Research shows that there is variability in the accumulation of amyloid-beta proteins and other markers, helping to establish a comprehensive database for studying gender differences. Using these models, researchers can understand how genetic variables interact with each other and impact cell biology.
However, challenges remain. So far, the vast majority of iPSC lines used are derived from males, which may lead to an imbalance in results. Scientists continue to work towards achieving better representation of women in research, opening the door to a more comprehensive understanding of pathological behaviors.
Look
To the Future with SABV Policy 2.0
Ten years of the Sex-Based Study Requirements (SABV) policy reflects the ongoing need for improvements in neuroscience research. The focus of scientists on the requirements of this policy reflects the growing awareness of the importance of sex differences. Agnes Lacroix believes it is time to reevaluate the current requirements and the possibility of developing a new policy that promotes research in this area.
It is crucial to include women in all scientific studies because sex is seen as a factor influencing various aspects of brain behavior and diseases. Although studies highlight the differences, this does not necessarily mean favoring one sex over the other. The most significant challenge also lies in how to interpret gender data and provide a balanced view of the results.
Shansky emphasizes the importance of developing data analysis tools and improving models, such as incorporating environmental factors that affect health and disease. The ambition now is to shift from attention solely on biological differences to understanding more complex patterns such as gender identity, which helps guide future research more accurately.
Therefore, the outlook remains generally positive regarding the SABV policy. Ongoing research shows how outdated hypotheses about brain function are being challenged, opening new avenues for innovation and discovery in the field of neuroscience.
Source link: https://www.the-scientist.com/xx-marks-the-spot-addressing-sex-bias-in-neuroscience-72129
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