Analysis from Weill Cornell Drugs reveals that astrocyte receptors influence cognitive capabilities in a different way in women and men, suggesting a necessity for sex-specific approaches in growing therapies focusing on these mind cells.
Scientists at Weill Cornell Drugs have found the primary proof that receptors in astrocytes, mind cells that help and regulate neurons, can have contrasting results on cognitive operate in female and male preclinical fashions. This analysis highlights the position of astrocytes in contributing to gender-specific mind mechanisms.
Whereas many research have examined the behavioral results of astrocytic receptors, none of them have addressed whether or not organic intercourse performs a task and most have examined solely males. This examine, revealed on Could 24 in Cell Experiences, challenges the long-standing assumption that astrocytic signaling has related cognitive results in each sexes.
“Our examine reveals that beforehand reported cognitive results in males can’t be extrapolated to females,” stated Dr. Anna G. Orr, the Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Analysis and an assistant professor of neuroscience within the Feil Household Mind and Thoughts Analysis Institute and the Helen and Robert Appel Alzheimer’s Analysis Institute at Weill Cornell Drugs.
Adjustments in astrocytic receptors are seen in numerous neurological situations with identified intercourse variations, together with neurodegenerative issues, schizophrenia, stroke, and epilepsy. Nevertheless, the mechanisms selling intercourse variations stay poorly understood.
How do Male and Feminine Brains Differ?
Within the examine, Dr. Samantha M. Meadows, first writer and former graduate scholar within the Orr lab, targeted on mGluR3, a predominant glutamate receptor in astrocytes and a top-altered gene in dementia. The crew used gene enhancing and stimulation of engineered receptors in animal fashions to selectively manipulate astrocytes and study the results of mGluR3 and associated receptors on studying, reminiscence, and different cognitive and behavioral outcomes.
The researchers discovered that growing astrocytic mGluR3 ranges enhanced reminiscence in older females and lowering these ranges was ample to impair reminiscence in younger females, demonstrating that mGluR3 promotes reminiscence recall in females. Nevertheless, in males, lowering mGluR3 enhanced reminiscence, and growing the receptor had no results. “Curiously, the cognitive influence of those receptors just isn’t conserved amongst sexes,” Dr. Meadows stated.
This picture of the mouse hippocampus, part of the mind concerned in studying and reminiscence, reveals mGluR3 receptors on astrocytes (inexperienced), neurons (crimson), and cell nuclei (blue). Credit score: Orr Lab
To grasp if these divergent results have been distinctive to mGluR3 or mirrored a broader function of astrocytic receptor signaling, Dr. Meadows labored with co-author Dr. Adam L. Orr, an assistant professor of analysis in neuroscience within the Mind and Thoughts Analysis Institute and the Appel Alzheimer’s Illness Analysis Institute, to selectively stimulate completely different astrocytic receptors whereas mice carried out duties involving studying and reminiscence.
To their shock, the crew discovered additional proof that receptor activation brought about both reminiscence enhancement or impairment, relying on organic intercourse. “Regular mind operate appears to require a sex-specific steadiness in astrocytic signaling,” Dr. Adam Orr stated.
This examine means that mGluR3 modulators being developed for treating issues equivalent to schizophrenia and anxiousness might have additional examine to evaluate their influence on completely different sexes. “Therapeutics influencing astrocytic receptors might trigger sex-specific cognitive results partly because of the divergent roles of astrocytes in women and men,” stated Dr. Anna Orr.
The lab is investigating what might trigger the differential results and if different mind capabilities are additionally modified in a sex-specific manner.
Reference: “Hippocampal astrocytes induce sex-dimorphic results on reminiscence” by Samantha M. Meadows, Fernando Palaguachi, Minwoo Wendy Jang, Avital Licht-Murava, Daniel Barnett, Until S. Zimmer, Constance Zhou, Samantha R. McDonough, Adam L. Orr and Anna G. Orr, 24 Could 2024, Cell Experiences.
DOI: 10.1016/j.celrep.2024.114278