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
AI Struggles with Abstract Thought: Study Reveals GPT-4’s Limits
While GPT-4 performs well in structured reasoning tasks, a new study shows that its ability to adapt to variations is weak—suggesting AI still lacks true abstract understanding and flexibility in decision-making. Artificial Intelligence (AI), [...]
Turning Off Nerve Signals: Scientists Develop Promising New Pancreatic Cancer Treatment
Pancreatic cancer reprograms nerve cells to fuel its growth, but blocking these connections can shrink tumors and boost treatment effectiveness. Pancreatic cancer is closely linked to the nervous system, according to researchers from the [...]
New human antibody shows promise for Ebola virus treatment
New research led by scientists at La Jolla Institute for Immunology (LJI) reveals the workings of a human antibody called mAb 3A6, which may prove to be an important component for Ebola virus therapeutics. [...]
Early Alzheimer’s Detection Test – Years Before Symptoms Appear
A new biomarker test can detect early-stage tau protein clumping up to a decade before it appears on brain scans, improving early Alzheimer’s diagnosis. Unlike amyloid-beta, tau neurofibrillary tangles are directly linked to cognitive decline. Years [...]
New mpox variant can spread rapidly across borders
International researchers, including from DTU National Food Institute, warn that the ongoing mpox outbreak in the Democratic Republic of the Congo (DRC) has the potential to spread across borders more rapidly. The mpox virus [...]
How far would you trust AI to make important decisions?
From tailored Netflix recommendations to personalized Facebook feeds, artificial intelligence (AI) adeptly serves content that matches our preferences and past behaviors. But while a restaurant tip or two is handy, how comfortable would you [...]
Can AI Really Think? Research Reveals Gaps in Logical Execution
While AI models can break down problems into structured steps, new research reveals they still fail at basic arithmetic and fact-checking—raising questions about their true reasoning abilities. Large Language Models (LLMs) have become indispensable [...]
Scientists Just Made Cancer Radiation Therapy Smarter, Safer, and More Precise
Scientists at UC San Francisco have developed a revolutionary cancer treatment that precisely targets tumors with radiation while sparing healthy tissues. By using a KRAS-targeting drug to mark cancer cells and attaching a radioactive [...]
Superbugs Are Losing to Science, Light, and a Little Spice
Texas A&M researchers have found that curcumin, when activated by light, can weaken antibiotic-resistant bacteria, restoring the effectiveness of conventional antibiotics. Curcumin: A Surprising Ally Against Superbugs In 2017, a woman admitted to a [...]
New Research Shatters the Perfect Pitch Myth
For decades, people believed absolute pitch was an exclusive ability granted only to those with the right genetics or early music training. But new research from the University of Surrey proves otherwise. It’s been [...]
Why Some Drinkers Suffer Devastating Liver Damage While Others Don’t
A study from Keck Medicine of USC found that heavy drinkers with diabetes, high blood pressure, or a large waistline are up to 2.4 times more likely to develop advanced liver disease. These conditions may amplify [...]
“Good” Cholesterol Could Be Bad for Your Eyes – New Study Raises Concerns
‘Good’ cholesterol may be linked to an increased risk of glaucoma in individuals over 55, while, paradoxically, ‘bad’ cholesterol may be associated with a lower risk. These findings challenge conventional beliefs about factors that [...]
Reawakening Dormant Nerve Cells: Groundbreaking Neurotechnology Restores Motor Function
A new electrical stimulation therapy for spinal muscle atrophy (SMA) has shown promise in reactivating motor neurons and improving movement. In a pilot clinical trial, three patients who received spinal cord stimulation for one [...]
AI’s Energy Crisis Solved? A Revolutionary Magnetic Chip Could Change Everything
AI is evolving at an incredible pace, but its growing energy demands pose a major challenge. Enter spintronic devices—new technology that mimics the brain’s efficiency by integrating memory and processing. Scientists in Japan have [...]
Nanotechnology for oil spill response and cleanup in coastal regions
(Nanowerk News) Cleaning up after a major oil spill is a long, expensive process, and the damage to a coastal region’s ecosystem can be significant. This is especially true for the world’s Arctic region, [...]
The Role of Nanotechnology in Space Exploration
Nanotechnology, which involves working with materials at the atomic or molecular level, is becoming increasingly important in space exploration. By improving strength, thermal stability, electrical conductivity, and radiation resistance, nanotechnology is helping create lighter, more [...]
