The dense bands of neurons pictured are the 2 blades of the dentate gyrus of the hippocampus within the mind. Most nuclei are stained teal, however the dentate cells which have nuclei stained pink have been activated when the mouse entered a threatening setting. Overactivity on this area is linked to avoidance behaviors and heightened nervousness. Credit score: Nicole Politowska
Elevated threat for nervousness could start earlier than delivery, formed by an infection or nerve-racking occasions throughout being pregnant, in line with a brand new preclinical research from researchers at Weill Cornell Drugs. Whereas scientists have lengthy recognized that maternal problem throughout being pregnant could increase a baby’s threat for psychiatric sickness, the organic pathways between these prenatal experiences and later psychological well being have been unclear.
The research, printed Sept. 10 in Cell Experiences, focuses on a area of the mind referred to as the ventral dentate gyrus (vDG), a part of the hippocampus that helps an individual assess threats within the setting. The researchers found that adversity within the womb configured a small proportion of those mind cells to be overly energetic when confronted with a threatening scenario, making a vulnerability to nervousness.
“Our data reveal prenatal adversity left lasting imprints on the neurons of the vDG linking gestational environment to anxiety-like behavior,” stated Dr. Miklos Toth, the Arleen B. Rifkind, M.D. Professor within the Division of Pharmacology at Weill Cornell Drugs, who co-led the analysis. “This mechanism may help explain the persistent stress sensitivity and avoidance seen in some individuals with innate anxiety.”
Lasting imprints from the womb
To imitate hostile circumstances within the womb, the researchers used a mouse mannequin that develops irregular immune exercise throughout being pregnant. When examined, their genetically regular offspring grew as much as present traditional indicators of hysteria, resembling avoiding open areas and over-responding to emphasize. However how does an inflammatory setting within the womb trigger lasting adjustments within the mind which will result in nervousness?
The group analyzed DNA methylation patterns in particular person neurons of the vDG. These chemical tags assist management which genes are turned on and off. Additionally they used single-cell RNA sequencing to map the genes that have been activated abnormally. These adjustments are referred to as “epigenetic” as a result of they do not alter the precise genetic code however have an effect on how cells learn and use that code.
Surprisingly, the researchers uncovered 1000’s of web sites the place DNA methylation was altered, particularly in areas that act as “on-off switches” for genes controlling synapses—the connections that permit neurons to speak. They noticed that some neurons have been extra affected than others.
When the mice have been uncovered to a threatening setting, probably the most closely reprogrammed neurons grew to become hyperactive. These neurons exhibited each altered DNA methylation and irregular expression of genes associated to synaptic operate.
“Overall, these epigenetic changes are instructing certain neurons in the vDG to respond differently in adulthood when faced with unsafe environments,” defined Dr. Kristen Pleil, affiliate professor of pharmacology at Weill Cornell Drugs, who co-led this analysis. “The neurons show too much activity, ultimately contributing to the mice perceiving the environment as more threatening than it actually is.”
Graphical summary. Credit score: Cell Experiences (2025). DOI: 10.1016/j.celrep.2025.116219
Reprogramming habits
The researchers then monitored these neurons in actual time. In management mice, exercise within the vDG remained regular when shifting from protected to dangerous areas of a maze. However in mice uncovered to prenatal adversity, exercise surged as quickly as they began fascinated with transitioning from security right into a threatening house.
This “ramping up” of exercise seems to encode an exaggerated notion of hazard, driving avoidance and anxious habits. “The mice seem to anticipate the danger, so the increased activity of the neurons is not a consequence of going into the threatening environment, but precedes it,” Dr. Pleil stated.
This research supplies one of many clearest mechanistic hyperlinks but between prenatal setting, epigenetic change and psychiatric threat, however is barely a place to begin. The researchers plan to tease out extra mechanistic particulars.
“A mouse may have almost 400,000 cells in the vDG, but only a few thousand are impacted during pregnancy. Next, we really want to understand why these certain cells are epigenetically programmed,” stated Dr. Toth.
A greater understanding of this mechanism could assist information the seek for comparable epigenetic signatures in folks, which may function early biomarkers of threat. The precise synapse-related genes which might be abnormally programmed in these “primed” neurons may additionally doubtlessly result in therapeutic targets.
The findings underscore the significance of maternal well being throughout being pregnant—not only for bodily outcomes like delivery weight, but in addition for shaping long-term mind operate.
Extra data:
Anika Nabila et al, Hostile gestational setting configures a subpopulation of ventral dentate granule cells for recruitment to drive innate nervousness, Cell Experiences (2025). DOI: 10.1016/j.celrep.2025.116219
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Weill Cornell Medical School
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Irritation throughout being pregnant could prime offspring for nervousness (2025, September 10)
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