Research from Weill Cornell Medicine reveals that astrocyte receptors impact cognitive functions differently in males and females, suggesting a need for sex-specific approaches in developing treatments targeting these brain cells.
Scientists at Weill Cornell Medicine have discovered the first evidence that receptors in astrocytes, brain cells that support and regulate neurons, can have contrasting effects on cognitive function in male and female preclinical models. This research highlights the role of astrocytes in contributing to gender-specific brain mechanisms.
While many studies have tested the behavioral effects of astrocytic receptors, none of them have addressed whether biological sex plays a role and most have tested only males. This study, published on May 24 in Cell Reports, challenges the long-standing assumption that astrocytic signaling has similar cognitive effects in both sexes.
“Our study reveals that previously reported cognitive effects in males can’t be extrapolated to females,” said Dr. Anna G. Orr, the Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Research and an assistant professor of neuroscience in the Feil Family Brain and Mind Research Institute and the Helen and Robert Appel Alzheimer’s Research Institute at Weill Cornell Medicine.
Changes in astrocytic receptors are seen in various neurological conditions with known sex differences, including neurodegenerative disorders, schizophrenia, stroke, and epilepsy. However, the mechanisms promoting sex differences remain poorly understood.
How do Male and Female Brains Differ?
In the study, Dr. Samantha M. Meadows, first author and former graduate student in the Orr lab, focused on mGluR3, a predominant glutamate receptor in astrocytes and a top-altered gene in dementia. The team used gene editing and stimulation of engineered receptors in animal models to selectively manipulate astrocytes and examine the effects of mGluR3 and related receptors on learning, memory, and other cognitive and behavioral outcomes.
The researchers found that increasing astrocytic mGluR3 levels enhanced memory in older females and reducing these levels was sufficient to impair memory in young females, demonstrating that mGluR3 promotes memory recall in females. However, in males, reducing mGluR3 enhanced memory, and increasing the receptor had no effects. “Interestingly, the cognitive impact of these receptors is not conserved among sexes,” Dr. Meadows said.
This image of the mouse hippocampus, a part of the brain involved in learning and memory, shows mGluR3 receptors on astrocytes (green), neurons (red), and cell nuclei (blue). Credit: Orr Lab
To understand if these divergent effects were unique to mGluR3 or reflected a broader feature of astrocytic receptor signaling, Dr. Meadows worked with co-author Dr. Adam L. Orr, an assistant professor of research in neuroscience in the Brain and Mind Research Institute and the Appel Alzheimer’s Disease Research Institute, to selectively stimulate different astrocytic receptors while mice performed tasks involving learning and memory.
To their surprise, the team found further evidence that receptor activation caused either memory enhancement or impairment, depending on biological sex. “Normal brain function seems to require a sex-specific balance in astrocytic signaling,” Dr. Adam Orr said.
This study suggests that mGluR3 modulators being developed for treating disorders such as schizophrenia and anxiety may need further study to assess their impact on different sexes. “Therapeutics influencing astrocytic receptors may cause sex-specific cognitive effects in part due to the divergent roles of astrocytes in males and females,” said Dr. Anna Orr.
The lab is investigating what may cause the differential effects and if other brain functions are also changed in a sex-specific way.
Reference: “Hippocampal astrocytes induce sex-dimorphic effects on memory” by Samantha M. Meadows, Fernando Palaguachi, Minwoo Wendy Jang, Avital Licht-Murava, Daniel Barnett, Till S. Zimmer, Constance Zhou, Samantha R. McDonough, Adam L. Orr and Anna G. Orr, 24 May 2024, Cell Reports.
DOI: 10.1016/j.celrep.2024.114278
News
Lockdowns prematurely aged teenagers’ brains, study suggests
Teenage girls' brains may have prematurely aged by up to four years during the Covid pandemic, an American study suggests. Adolescent boys weren't immune either with their brain's also showing signs of undue wear [...]
Long COVID Still a Mystery: Routine Labs Show No Reliable Biomarkers
Routine lab tests are not reliable for diagnosing Long COVID, according to a new study. The research found that no clinical lab values could serve as biomarkers, highlighting the need to focus on symptoms [...]
Tiny magnetic robots could treat bleeds in the brain
Researchers have created nanoscale robots which could be used to manage bleeds in the brain caused by aneurysms. The development could enable precise, relatively low-risk treatment of brain aneurysms, which cause around 500,000 deaths globally [...]
Turning Mosquito Spit Into a Weapon Against the West Nile Virus and Other Deadly Diseases
Anita Saraf investigates mosquito saliva to understand how viruses like dengue and West Nile are transmitted, using mass spectrometry to identify potential targets for vaccines and treatments. You might guess it’d be tough to [...]
Ethics in Nanomedicine: Key Issues and Principles
Nanomedicine, a branch of nanotechnology, is revolutionizing healthcare by enabling the manipulation of materials at the nanoscale to diagnose, treat, and prevent diseases. Unlike traditional treatments, nanoparticles (NPs) are highly precise in targeting diseased [...]
A call for robust H5N1 influenza preparedness and response
As the global threat of H5N1 influenza looms with outbreaks across species and continents including the U.S., three international vaccine and public health experts say it is time to fully resource and support a [...]
Mucosal COVID-19 boosters outperform mRNA shots in preventing upper airway infections
In a recent study published in Nature Immunology, a team of researchers from the United States used non-human primate models to compare the protection conferred by an intramuscular booster dose of the bivalent messenger ribonucleic acid [...]
How Space Travel Really Changes Astronauts – From the Inside Out
International team reveals previously unknown effects on physiology that could shape the future of long-duration space missions. Researchers have discovered significant changes in the gut microbiome due to spaceflight, which affects host physiology and [...]
Breakthrough in blood stem cell development offers hope for leukemia and bone marrow failure
Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalized treatments for children with leukemia [...]
Scientists Develop Game-Changing Needle-Free COVID-19 Intranasal Vaccine
A new mucosal COVID-19 vaccine poised to revolutionize the delivery process is especially beneficial for those with a fear of needles. A next-generation COVID-19 mucosal vaccine is set to be a game-changer not only when delivering [...]
Scientists Develop All-in-One Solution To Catch and Destroy “Forever Chemicals”
A new water treatment system developed by UBC researchers efficiently removes and destroys PFAS pollutants using a dual-action catalyst, offering a sustainable and cost-effective solution for water purification challenges. Chemical engineers at the University of [...]
New method accelerates drug discovery from years to months
Researchers from the University of Cincinnati College of Medicine and Cincinnati Children's Hospital have found a new method to increase both speed and success rates in drug discovery. The study, published Aug. 30 in [...]
A new smart mask analyzes your breath to monitor your health
Your breath can give away a lot about you. Each exhalation contains all sorts of compounds, including possible biomarkers for disease or lung conditions, that could give doctors a valuable insight into your health. [...]
Study reveals the role of blood clotting in COVID-19
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks [...]
A Novel Cancer Vaccine Combining Nano-11 and ADU-S100
In a recent article published in npj Vaccines, researchers detailed the development of a novel cancer vaccine that combines a plant-derived nanoparticle adjuvant, Nano-11, with a clinically tested STING agonist, ADU-S100. The primary objective was [...]
AI spots cancer and viral infections with nanoscale precision
Researchers have developed an artificial intelligence which can differentiate cancer cells from normal cells, as well as detect the very early stages of viral infection inside cells. The findings, published today in a study [...]
