Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities
Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors specifically in adult...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | Neurobiology of Stress |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289525000438 |
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| author | Keren Shoshani-Haye Gilgi Friedlander Ofra Golani Suellen Almeida-Correa Yair Shemesh Alon Chen |
| author_facet | Keren Shoshani-Haye Gilgi Friedlander Ofra Golani Suellen Almeida-Correa Yair Shemesh Alon Chen |
| author_sort | Keren Shoshani-Haye |
| collection | DOAJ |
| description | Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors specifically in adult male mice. To investigate potential neurodevelopmental disruptions, we analyzed the medial prefrontal cortex (mPFC) at key postnatal stages. RNA sequencing at postnatal day 1 (P1) revealed significant transcriptional changes, particularly in genes associated with neuronal migration and differentiation, with a diminished effect by P14. Histological analysis identified a transient imbalance in inhibitory neuron subpopulations, PNS decreased the density of early-born neurons derived from the medial ganglionic eminence (MGE) while increasing late-born neurons derived from the caudal ganglionic eminence (CGE) at P1. EdU labeling confirmed that these shifts were time- and subtype-specific, affecting inhibitory neuron proliferation at distinct embryonic stages. By P15, these neuroanatomical alterations largely resolved, yet behavioral abnormalities persisted into adulthood. Our findings suggest that PNS disrupts inhibitory neuron development during a critical early window, leading to lasting behavioral consequences despite the transient nature of anatomical changes. This study highlights the selective vulnerability of inhibitory neuron subtypes to early-life stress and provides insight into potential mechanisms underlying stress-related psychiatric disorders. |
| format | Article |
| id | doaj-art-a05f317980c442b9a8281bea9f73a898 |
| institution | Kabale University |
| issn | 2352-2895 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj-art-a05f317980c442b9a8281bea9f73a8982025-08-20T03:43:44ZengElsevierNeurobiology of Stress2352-28952025-09-013810074910.1016/j.ynstr.2025.100749Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalitiesKeren Shoshani-Haye0Gilgi Friedlander1Ofra Golani2Suellen Almeida-Correa3Yair Shemesh4Alon Chen5Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, IsraelThe Crown Genomics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, IsraelMICC Cell Observatory, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel; Corresponding author. Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors specifically in adult male mice. To investigate potential neurodevelopmental disruptions, we analyzed the medial prefrontal cortex (mPFC) at key postnatal stages. RNA sequencing at postnatal day 1 (P1) revealed significant transcriptional changes, particularly in genes associated with neuronal migration and differentiation, with a diminished effect by P14. Histological analysis identified a transient imbalance in inhibitory neuron subpopulations, PNS decreased the density of early-born neurons derived from the medial ganglionic eminence (MGE) while increasing late-born neurons derived from the caudal ganglionic eminence (CGE) at P1. EdU labeling confirmed that these shifts were time- and subtype-specific, affecting inhibitory neuron proliferation at distinct embryonic stages. By P15, these neuroanatomical alterations largely resolved, yet behavioral abnormalities persisted into adulthood. Our findings suggest that PNS disrupts inhibitory neuron development during a critical early window, leading to lasting behavioral consequences despite the transient nature of anatomical changes. This study highlights the selective vulnerability of inhibitory neuron subtypes to early-life stress and provides insight into potential mechanisms underlying stress-related psychiatric disorders.http://www.sciencedirect.com/science/article/pii/S2352289525000438Prenatal stressMedial prefrontal cortexInhibitory neuronsStress related behaviorNeurodevelopment |
| spellingShingle | Keren Shoshani-Haye Gilgi Friedlander Ofra Golani Suellen Almeida-Correa Yair Shemesh Alon Chen Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities Neurobiology of Stress Prenatal stress Medial prefrontal cortex Inhibitory neurons Stress related behavior Neurodevelopment |
| title | Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities |
| title_full | Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities |
| title_fullStr | Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities |
| title_full_unstemmed | Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities |
| title_short | Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities |
| title_sort | prenatal stress induces transient developmental alterations in distinct gabaergic populations and leads to long lasting behavioral abnormalities |
| topic | Prenatal stress Medial prefrontal cortex Inhibitory neurons Stress related behavior Neurodevelopment |
| url | http://www.sciencedirect.com/science/article/pii/S2352289525000438 |
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