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
Brazilian Tree Compounds Fight COVID-19 on Multiple Fronts
Scientists found compounds in a Brazilian tree that hit SARS-CoV-2 on multiple fronts, revealing a promising new lead in the search for COVID-19 treatments. Researchers have found that galloylquinic acids extracted from the leaves [...]
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
New injectable treatment helps the brain rebuild after stroke
Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke. In experiments with mice, the material transformed the cavity created [...]
Scientists Discover a Hidden “Immune Organ” Inside the Skull
Researchers discovered lymph node-like immune hubs inside skull bone marrow that appear to act as rapid-response centers for the brain. For decades, the brain was thought to operate largely apart from the immune system. [...]
Engineered tRNAs and lipid nanoparticles target nonsense mutation cystic fibrosis
Researchers have developed a potential new approach for treating a form of cystic fibrosis caused by so-called nonsense mutations, combining chemically modified transfer RNAs with lipid nanoparticles designed to deliver the therapy directly to [...]
New pancreatic cancer drug carries a $39,800 monthly list price
A groundbreaking treatment for one of the most common forms of pancreatic cancer has been approved in pill form by the FDA. Revolution Medicines’ oral tablet daraxonrasib, branded as Rasonque, reduced the risk of [...]
Researchers Have Discovered a New Way To Reduce Chronic Nerve Pain
A cancer-linked protein called BRAF may help drive chronic nerve pain, and existing cancer drugs targeting it reduced pain sensitivity in preclinical models. Chronic nerve pain can persist long after an injury and often [...]
Our books now available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
Quantum-Enabled Regenerative Health: Reimagining Wellness, Precision Health and Longevity Medicine
Introduction Healthcare is approaching a frontier where the quantum portfolio could influence not only how disease is diagnosed and treated, but how health itself is measured, modeled, predicted and preserved. Quantum computing, quantum simulation, [...]
FDA Clears First-of-Its-Kind Nonmedication Treatment for PTSD
The FDA has cleared a system that uses brain activity data to personalize magnetic stimulation for PTSD, adding a new nonmedication treatment option. Every day in the United States, approximately 17.5 veterans die by suicide, [...]
FDA approves breakthrough drug to treat advanced pancreatic cancer
The Food and Drug Administration (FDA) approved on Wednesday a drug that could extend the survival of those with metastatic pancreatic cancer. The drug, called daraxonrasib, will be sold under the brand name Rasonque [...]
AI Decodes a Hidden DNA Signal Linked to Disease-Causing Mutations
Machine learning identifies the likely “initiator” and enables new predictions about DNA mutations that can cause disease. Every human cell depends on tens of thousands of genes being switched on at the right time [...]
