Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions
Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation....
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Neurobiology of Stress |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289525000165 |
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| author | Huba Szebik Christina Miskolczi Bíborka Bruzsik Gyula Balla Soma Szabó László Biró Éva Mikics |
| author_facet | Huba Szebik Christina Miskolczi Bíborka Bruzsik Gyula Balla Soma Szabó László Biró Éva Mikics |
| author_sort | Huba Szebik |
| collection | DOAJ |
| description | Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation. Here, we investigated region-specific, dynamic changes in SERT expression following aggressive interactions and in mice subjected to early-life social adversity. We found that aggressive encounters (resident-intruder test) triggered a significant, rapid increase in SERT immunoreactivity within 90 min, accompanied by neuronal activation in aggression-related brain regions, including the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), ventromedial hypothalamus (VMHvl), lateral habenula (LH), and dorsal raphe (DR), but not in the paraventricular thalamus (PVT). Notably, this SERT upregulation occurred across the aggression circuitry but was accompanied by a significant increase in 5-HT levels only in the mPFC, a key region in top-down regulation of social and aggressive behavior. This SERT upregulation was not observed following exposure to a non-social challenge, suggesting that it may be more specifically associated with social contexts. Using super-resolution microscopy, we identified an increased density of SERT localization points within serotonergic mPFC axons after an aggressive encounter. Social isolation during adolescence, a model of early social neglect, impaired this rapid SERT response, particularly in the ventral and medial orbitofrontal regions, and altered the relationship between SERT levels and aggression-related behaviors. These findings demonstrate that SERT expression undergoes rapid, experience-dependent plasticity in response to social aggression, and that early-life adversity disrupts this adaptive mechanism, providing new insights into the serotonergic regulation of aggression and its potential relevance for stress-related social dysfunctions. |
| format | Article |
| id | doaj-art-eeee95322a4847c482eb74498b9d4eba |
| institution | DOAJ |
| issn | 2352-2895 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj-art-eeee95322a4847c482eb74498b9d4eba2025-08-20T03:18:37ZengElsevierNeurobiology of Stress2352-28952025-05-013610072210.1016/j.ynstr.2025.100722Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactionsHuba Szebik0Christina Miskolczi1Bíborka Bruzsik2Gyula Balla3Soma Szabó4László Biró5Éva Mikics6Translational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary; Semmelweis University, Doctoral School, Budapest, HungaryTranslational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary; Semmelweis University, Doctoral School, Budapest, HungaryTranslational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryTranslational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryTranslational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryTranslational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary; Thalamus Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary; Corresponding author. Thalamus Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.Translational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary; Corresponding author.Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation. Here, we investigated region-specific, dynamic changes in SERT expression following aggressive interactions and in mice subjected to early-life social adversity. We found that aggressive encounters (resident-intruder test) triggered a significant, rapid increase in SERT immunoreactivity within 90 min, accompanied by neuronal activation in aggression-related brain regions, including the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), ventromedial hypothalamus (VMHvl), lateral habenula (LH), and dorsal raphe (DR), but not in the paraventricular thalamus (PVT). Notably, this SERT upregulation occurred across the aggression circuitry but was accompanied by a significant increase in 5-HT levels only in the mPFC, a key region in top-down regulation of social and aggressive behavior. This SERT upregulation was not observed following exposure to a non-social challenge, suggesting that it may be more specifically associated with social contexts. Using super-resolution microscopy, we identified an increased density of SERT localization points within serotonergic mPFC axons after an aggressive encounter. Social isolation during adolescence, a model of early social neglect, impaired this rapid SERT response, particularly in the ventral and medial orbitofrontal regions, and altered the relationship between SERT levels and aggression-related behaviors. These findings demonstrate that SERT expression undergoes rapid, experience-dependent plasticity in response to social aggression, and that early-life adversity disrupts this adaptive mechanism, providing new insights into the serotonergic regulation of aggression and its potential relevance for stress-related social dysfunctions.http://www.sciencedirect.com/science/article/pii/S2352289525000165AggressionSerotoninPrefrontal cortexPost-weaning social isolationSerotonin transporterSuper-resolution |
| spellingShingle | Huba Szebik Christina Miskolczi Bíborka Bruzsik Gyula Balla Soma Szabó László Biró Éva Mikics Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions Neurobiology of Stress Aggression Serotonin Prefrontal cortex Post-weaning social isolation Serotonin transporter Super-resolution |
| title | Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| title_full | Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| title_fullStr | Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| title_full_unstemmed | Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| title_short | Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| title_sort | dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions |
| topic | Aggression Serotonin Prefrontal cortex Post-weaning social isolation Serotonin transporter Super-resolution |
| url | http://www.sciencedirect.com/science/article/pii/S2352289525000165 |
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