Summary: Researchers found that astrocyte receptors impact cognitive function differently in male and female preclinical models. The study reveals that astrocyte signaling cannot be assumed to have the same cognitive effects across sexes.
This finding suggests that therapies targeting astrocytic receptors may need to take sex-specific impacts into account.
Highlights:
- Astrocyte receptors affect memory differently in male and female brains.
- Changes in astrocytic receptors are linked to various neurological conditions with known sex differences.
- The study challenges the hypothesis that astrocyte signaling has similar cognitive effects in both sexes.
Source: Weill Cornell University
Weill Cornell Medicine scientists have discovered the first evidence that astrocyte receptors can trigger opposing effects on cognitive function in male and female preclinical models.
The results indicate that astrocytes, brain cells that support and regulate neurons, play a key role in sex-specific brain mechanisms.
Although many studies have tested the behavioral effects of astrocyte receptors, none of them have examined whether biological sex plays a role and most have only tested males.
This study, published on May 24 in Cell Reportschallenges the long-standing assumption that astrocyte signaling has similar cognitive effects in both sexes.
“Our study reveals that cognitive effects previously reported in men cannot be extrapolated to women,” said Dr. Anna G. Orr, Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Research and assistant professor of neuroscience in the brain of the Feil family. and Mind Research Institute and the Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell Medicine.
Changes in astrocytic receptors are observed in a variety of neurological conditions with known sex differences, including neurodegenerative disorders, schizophrenia, stroke, and epilepsy. However, the mechanisms driving 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 highly 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 levels of mGluR3 improved memory in older women and that reducing these levels was sufficient to impair memory in younger women, demonstrating that mGluR3 promotes memory recall in older women. women.
However, in men, mGluR3-enhanced memory reduction and receptor augmentation had no effect. “Interestingly, the cognitive impact of these receptors is not conserved between the sexes,” Dr. Meadows said.
To understand whether 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, research assistant professor of neuroscience at the Brain and Mind Research Institute and the Appel Alzheimer’s Disease Research Institute, to selectively stimulate different astrocyte receptors while mice performed tasks involving learning and memory.
To their surprise, the team found further evidence that receptor activation led to either improved or impaired memory, depending on biological sex. “Normal brain function appears to require a sex-specific balance in astrocyte signaling,” said Dr. Adam Orr.
This study suggests that mGluR3 modulators being developed to treat disorders such as schizophrenia and anxiety may require further study to assess their impact on different sexes.
“Therapies influencing astrocyte receptors may cause sex-specific cognitive effects, in part because of the divergent roles of astrocytes in men and women,” said Dr. Anna Orr.
The lab is investigating what may cause these differential effects and whether other brain functions are also altered in a sex-specific manner.
About this news from research on memory and neuroscience
Author: Barbara Prempeh
Source: Weill Cornell University
Contact: Barbara Prempeh – Weill Cornell University
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Hippocampal astrocytes mediate sexual dimorphism effects on memory” by Anna G. Orr et al. Cell
Abstract
Hippocampal astrocytes induce sexual dimorphism effects on memory
Strong points
- Changes in astrocytic mGluR3 levels induce sex-dependent effects on spatial memory
- Astrocyte mGluR3 modulates recall-seeking behavior in a sex-specific manner
- Astrocyte Genter exit and Gs receptors have opposite effects of sexual dimorphism on memory
Summary
Astrocyte receptors influence cognitive function and may promote behavioral deficits in disease. These effects may vary depending on variables such as biological sex, but it is not known whether the effects of astrocyte receptors are sex dependent.
We exploited in vivo gene editing and chemogenetics to examine the roles of astrocyte receptors in spatial memory and other processes. We show that reductions in metabotropic glutamate receptor 3 (mGluR3), the major astrocytic glutamate receptor in adults, impairs memory in females but improves memory in males.
Similarly, increasing astrocytic mGluR3 levels has sex-dependent effects and improves memory in women. Manipulations of mGluR3 also alter spatial search strategies during recall in a sex-specific manner.
Furthermore, acute chemogenetic stimulation of Genter exit-coupled or Gs-coupled receptors in hippocampal astrocytes induce bidirectional and sexually dimorphic effects on memory.
Thus, astrocytes are sex-dependent modulators of cognitive function and may promote sex differences in aging and disease.
News Source : neurosciencenews.com
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