Pub Date : 2025-11-05DOI: 10.1016/j.physbeh.2025.115159
Rui Wang , Dan Fang , Yuxin Kang , Weining Wang , Yutong Guo , Haiyang Kang , Jinkun Fan , Shuoshuo Yin , Yuanzhan Deng , Zhiping Hu , Hu Qiao , Shuang Wang
Pain is the most common adverse effect of orthodontic treatment. Transient receptor potential vanilla-like protein 4 (TRPV4) plays an important role in pain regulation, and central amygdala (CeA) is also an important nuclear mass in pain regulation, but there is a paucity of literature on the roles of TRPV4 in CeA on tooth movement pain. C57BL/6 J mice were divided into control group, 0 g group and 30 g group. After establishing the experimental tooth movement model, behavioral tests were first performed, which showed that pain behavior peaked on day 1 and then dropped to baseline on day 7. The 30 g group developed anxiety-like behavior after 14 days of application, and the degree increased over time. In addition, immunofluorescence staining and western blot was performed on CeA tissues. The results showed that tooth movement significantly increased the fluorescence intensity of TRPV4 and protein expression of TRPV4, NLRP3, P65 and the phosphorylation of P65 proteins in CeA. Administration of TRPV4 antagonists in CeA through intraperitoneal injection effectively alleviated tooth movement induced pain and anxiety-like behaviors. This suggests that TRPV4 within CeA may mediate the regulation of tooth movement pain through NLRP3-NF-κB signaling pathway, which not only clarify the mechanism of CeA regulating tooth movement pain, but also help regulating tooth movement pain precisely.
{"title":"Rising TRPV4 expression in the central nucleus of amygdala is involved in tooth movement pain","authors":"Rui Wang , Dan Fang , Yuxin Kang , Weining Wang , Yutong Guo , Haiyang Kang , Jinkun Fan , Shuoshuo Yin , Yuanzhan Deng , Zhiping Hu , Hu Qiao , Shuang Wang","doi":"10.1016/j.physbeh.2025.115159","DOIUrl":"10.1016/j.physbeh.2025.115159","url":null,"abstract":"<div><div>Pain is the most common adverse effect of orthodontic treatment. Transient receptor potential vanilla-like protein 4 (TRPV4) plays an important role in pain regulation, and central amygdala (CeA) is also an important nuclear mass in pain regulation, but there is a paucity of literature on the roles of TRPV4 in CeA on tooth movement pain. C57BL/6 J mice were divided into control group, 0 g group and 30 g group. After establishing the experimental tooth movement model, behavioral tests were first performed, which showed that pain behavior peaked on day 1 and then dropped to baseline on day 7. The 30 g group developed anxiety-like behavior after 14 days of application, and the degree increased over time. In addition, immunofluorescence staining and western blot was performed on CeA tissues. The results showed that tooth movement significantly increased the fluorescence intensity of TRPV4 and protein expression of TRPV4, NLRP3, P65 and the phosphorylation of P65 proteins in CeA. Administration of TRPV4 antagonists in CeA through intraperitoneal injection effectively alleviated tooth movement induced pain and anxiety-like behaviors. This suggests that TRPV4 within CeA may mediate the regulation of tooth movement pain through NLRP3-NF-κB signaling pathway, which not only clarify the mechanism of CeA regulating tooth movement pain, but also help regulating tooth movement pain precisely.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115159"},"PeriodicalIF":2.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.physbeh.2025.115156
Suheda Kaya , Serkan Kirik , Suat Tas , Dahiru Tanko , Tugce Keles , Irem Tasci , Sengul Dogan , Mehmet Baygin , Turker Tuncer
Background
One of the primary objectives of neuroscience is to gather information from the brain. Therefore, brain data are crucial for understanding its secrets, and one of the most affordable methods for collecting such data is electroencephalography (EEG). To capture meaningful information, machine learning models have been applied to EEG signals. In this research, our main goal is to investigate an innovative feature-extraction method on a new EEG dataset to obtain both accurate classification and interpretable results.
Material and Methods
First, we curated a novel EEG signal dataset comprising four classes: (i) hungry, (ii) thirsty, (iii) cigarette-addicted, and (iv) control. Using this dataset, we defined four cases: (1) hunger detection, (2) thirst detection, (3) nicotine-withdrawal detection, and (4) abnormality (hunger + thirst + nicotine-withdrawal) detection. To automatically detect these cases, we introduced a specialized transformer-based feature-extraction method. This transformer, called the Moon Star Transformer (MST), was deployed alongside a Transition Table Feature Extractor (TTFE) to form the Turker Pattern (TurkerPat). Feature selection, ensemble and iterative classification, and an interpretable results generator were then integrated into the TurkerPat-centric XFE framework to achieve both classification accuracy and interpretability.
Results
The proposed TurkerPat-centric XFE framework attained over 85 % classification accuracy using leave-one-subject-out cross-validation (LOSO CV). By applying Directed Lobish (DLob) for interpretable result generation, we obtained connectome diagrams for each defined case.
Conclusion
The classification and explainable results clearly demonstrate that the TurkerPat-centric XFE framework makes a significant contribution to both neuroscience and feature engineering.
{"title":"TurkerPat: EEG-Based detection of hunger, thirst, and nicotine withdrawal","authors":"Suheda Kaya , Serkan Kirik , Suat Tas , Dahiru Tanko , Tugce Keles , Irem Tasci , Sengul Dogan , Mehmet Baygin , Turker Tuncer","doi":"10.1016/j.physbeh.2025.115156","DOIUrl":"10.1016/j.physbeh.2025.115156","url":null,"abstract":"<div><h3>Background</h3><div>One of the primary objectives of neuroscience is to gather information from the brain. Therefore, brain data are crucial for understanding its secrets, and one of the most affordable methods for collecting such data is electroencephalography (EEG). To capture meaningful information, machine learning models have been applied to EEG signals. In this research, our main goal is to investigate an innovative feature-extraction method on a new EEG dataset to obtain both accurate classification and interpretable results.</div></div><div><h3>Material and Methods</h3><div>First, we curated a novel EEG signal dataset comprising four classes: (i) hungry, (ii) thirsty, (iii) cigarette-addicted, and (iv) control. Using this dataset, we defined four cases: (1) hunger detection, (2) thirst detection, (3) nicotine-withdrawal detection, and (4) abnormality (hunger + thirst + nicotine-withdrawal) detection. To automatically detect these cases, we introduced a specialized transformer-based feature-extraction method. This transformer, called the Moon Star Transformer (MST), was deployed alongside a Transition Table Feature Extractor (TTFE) to form the Turker Pattern (TurkerPat). Feature selection, ensemble and iterative classification, and an interpretable results generator were then integrated into the TurkerPat-centric XFE framework to achieve both classification accuracy and interpretability.</div></div><div><h3>Results</h3><div>The proposed TurkerPat-centric XFE framework attained over 85 % classification accuracy using leave-one-subject-out cross-validation (LOSO CV). By applying Directed Lobish (DLob) for interpretable result generation, we obtained connectome diagrams for each defined case.</div></div><div><h3>Conclusion</h3><div>The classification and explainable results clearly demonstrate that the TurkerPat-centric XFE framework makes a significant contribution to both neuroscience and feature engineering.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115156"},"PeriodicalIF":2.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.physbeh.2025.115160
Felipe Forero-Castillo , Daniel Enrique Gonzalez-Escobar , Julian Humberto Avalo-Zuluaga , Daniela Baptista-de-Souza , Lucas Canto-de-Souza , Carlos C. Crestani , Javier Leonardo Rico , Ricardo Luiz Nunes-de-Souza
Anxiety disorders are increasingly prevalent, and the exposure to psychosocial stress is an important influencing factor; however, the underlying neurobiological mechanisms in female populations remain largely unexplored in animal models. This study investigated the role of the corticotropin-releasing factor type 1 receptor (CRF1R) in the bed nucleus of the stria terminalis (BNST) in anxiety-like behaviors induced by vicarious social defeat stress in female and male mice. Swiss-Webster mice underwent 10 sessions of witnessing social defeat stress (WSDS) or witnessing non-aggressive interactions (WNAI). Subsequently, their behaviors were evaluated in the social interaction test (SIT). Twenty-four hours later, each mouse received treatment with the CRF1R antagonist, CP376395, and after 1 h, was exposed to the elevated plus maze (EPM). Immunofluorescence for c-Fos was employed to assess BNST activation. WSDS female mice exhibited anxiety-like behavior, which was effectively reversed by CP3763995. Additionally, these stressed females exhibited greater c-Fos expression in the ventral BNST, a response attenuated by CRF1 receptor blockade. Notably, no significant behavioral or neural activation changes were observed in males under identical conditions. These findings underscore a sex-specific role for CRF1R signaling in the BNST in mediating anxiety-like responses to vicarious stress, highlighting the relevance of this neurobiological mechanism as a potential target for female-focused therapeutic strategies.
{"title":"Evaluation of the role of CRFergic neurotransmission in anxiety and BNST neuronal activity in male and female mice exposed to psychosocial stress","authors":"Felipe Forero-Castillo , Daniel Enrique Gonzalez-Escobar , Julian Humberto Avalo-Zuluaga , Daniela Baptista-de-Souza , Lucas Canto-de-Souza , Carlos C. Crestani , Javier Leonardo Rico , Ricardo Luiz Nunes-de-Souza","doi":"10.1016/j.physbeh.2025.115160","DOIUrl":"10.1016/j.physbeh.2025.115160","url":null,"abstract":"<div><div>Anxiety disorders are increasingly prevalent, and the exposure to psychosocial stress is an important influencing factor; however, the underlying neurobiological mechanisms in female populations remain largely unexplored in animal models. This study investigated the role of the corticotropin-releasing factor type 1 receptor (CRF1R) in the bed nucleus of the stria terminalis (BNST) in anxiety-like behaviors induced by vicarious social defeat stress in female and male mice. Swiss-Webster mice underwent 10 sessions of witnessing social defeat stress (WSDS) or witnessing non-aggressive interactions (WNAI). Subsequently, their behaviors were evaluated in the social interaction test (SIT). Twenty-four hours later, each mouse received treatment with the CRF1R antagonist, CP376395, and after 1 h, was exposed to the elevated plus maze (EPM). Immunofluorescence for c-Fos was employed to assess BNST activation. WSDS female mice exhibited anxiety-like behavior, which was effectively reversed by CP3763995. Additionally, these stressed females exhibited greater c-Fos expression in the ventral BNST, a response attenuated by CRF1 receptor blockade. Notably, no significant behavioral or neural activation changes were observed in males under identical conditions. These findings underscore a sex-specific role for CRF1R signaling in the BNST in mediating anxiety-like responses to vicarious stress, highlighting the relevance of this neurobiological mechanism as a potential target for female-focused therapeutic strategies.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115160"},"PeriodicalIF":2.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.physbeh.2025.115157
T.L. Philbeck, R. Parrish Waters
Mice form social hierarchies that can determine access to limited resources and overall health. Accordingly, social rank strongly influences behavioral and physiological health. The Tube Test is an established method used to identify social rank in mice and its rapidity and simplicity have made it a popular tool to understand mouse social relationships; however, this test is not universally accepted as a reliable and objective measure of social dominance. To address its controversial validity, we compared performance in the Tube Test to home cage aggression, home cage activity, preputial gland size, and steroid hormone levels, all of which are indicators of dominance or social stress in mice, but are less utilized because of the high expense and intense labor involved. We used young adult male mice housed in dyads, and evaluated these measures over 29 days. To broaden the impact of this study, we used dyads of both outbred CD-1 and inbred C57 mice. Tube Test performance had no ability to predict qualities associated with behavioral or physiological dominance, suggesting that caution should be taken when using the Tube Test to predict dominance relationships in mice. Our study does, however, suggest that the Tube Test may offer some utility in alternative contexts.
{"title":"The Tube Test fails to predict social dominance in across two strains of mice","authors":"T.L. Philbeck, R. Parrish Waters","doi":"10.1016/j.physbeh.2025.115157","DOIUrl":"10.1016/j.physbeh.2025.115157","url":null,"abstract":"<div><div>Mice form social hierarchies that can determine access to limited resources and overall health. Accordingly, social rank strongly influences behavioral and physiological health. The Tube Test is an established method used to identify social rank in mice and its rapidity and simplicity have made it a popular tool to understand mouse social relationships; however, this test is not universally accepted as a reliable and objective measure of social dominance. To address its controversial validity, we compared performance in the Tube Test to home cage aggression, home cage activity, preputial gland size, and steroid hormone levels, all of which are indicators of dominance or social stress in mice, but are less utilized because of the high expense and intense labor involved. We used young adult male mice housed in dyads, and evaluated these measures over 29 days. To broaden the impact of this study, we used dyads of both outbred CD-1 and inbred C57 mice. Tube Test performance had no ability to predict qualities associated with behavioral or physiological dominance, suggesting that caution should be taken when using the Tube Test to predict dominance relationships in mice. Our study does, however, suggest that the Tube Test may offer some utility in alternative contexts.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115157"},"PeriodicalIF":2.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.physbeh.2025.115155
Memunat Diekololaoluwa Abiru , Sonita Wiah , Meghana Dachepalli , Amy D. Stringer , Michael R. Ruff , Scott M. Rawls
RAP-103 is an orally active, multi-chemokine receptor antagonist (CRA) that inhibits three different chemokine receptors (CCR2, CCR5 and CCR8). Planarians, the simplest animals with bilateral symmetry and CNS cephalization, are useful for screening putative therapeutics because they express neurotransmitter systems and display mammalian-like behaviors when exposed to addictive drugs. We investigated effects of RAP-103 on spontaneous planarian behaviors (light avoidance, motility) and withdrawal responses associated with methamphetamine (METH) abstinence. Acute RAP-103 exposure decreased light avoidance (0.1, 1 μM) and increased motility (1 μM). For both endpoints, RAP-103 displayed an inverted U-shape concentration-effect curve. Maraviroc (1, 10 μM), a CCR5 antagonist, decreased light avoidance (like RAP-103) but reduced motility. RS 504393 (1, 10 μM), a CCR2 antagonist, increased light avoidance and reduced motility. For METH abstinence experiments, planarians were exposed for 5 min to a concentration of METH (1 μM) that did not cause spontaneous behaviors and then removed and placed into water. Planarians were then tested for light avoidance and motility during both early abstinence (0–5 min post-METH exposure) and later abstinence (15–20 min post-METH exposure). Light avoidance was enhanced during early METH abstinence whereas motility was reduced during later abstinence. RAP-103 (0.01, 0.1, 1 μM), administered during METH abstinence, counteracted METH-induced light avoidance but did not rescue METH-induced motility deficits. Our results with planarians show that RAP-103 displays anxiolytic-like and motor-enhancing effects and counteracts METH abstinence-induced behaviors, highlighting the potential of RAP-103 as a chemokine-based CNS therapeutic.
{"title":"RAP-103, a multi-chemokine receptor antagonist, displays anxiolytic-like effects and normalizes methamphetamine abstinence-induced behaviors in planarians","authors":"Memunat Diekololaoluwa Abiru , Sonita Wiah , Meghana Dachepalli , Amy D. Stringer , Michael R. Ruff , Scott M. Rawls","doi":"10.1016/j.physbeh.2025.115155","DOIUrl":"10.1016/j.physbeh.2025.115155","url":null,"abstract":"<div><div>RAP-103 is an orally active, multi-chemokine receptor antagonist (CRA) that inhibits three different chemokine receptors (CCR2, CCR5 and CCR8). Planarians, the simplest animals with bilateral symmetry and CNS cephalization, are useful for screening putative therapeutics because they express neurotransmitter systems and display mammalian-like behaviors when exposed to addictive drugs. We investigated effects of RAP-103 on spontaneous planarian behaviors (light avoidance, motility) and withdrawal responses associated with methamphetamine (METH) abstinence. Acute RAP-103 exposure decreased light avoidance (0.1, 1 μM) and increased motility (1 μM). For both endpoints, RAP-103 displayed an inverted U-shape concentration-effect curve. Maraviroc (1, 10 μM), a CCR5 antagonist, decreased light avoidance (like RAP-103) but reduced motility. RS 504393 (1, 10 μM), a CCR2 antagonist, increased light avoidance and reduced motility. For METH abstinence experiments, planarians were exposed for 5 min to a concentration of METH (1 μM) that did not cause spontaneous behaviors and then removed and placed into water. Planarians were then tested for light avoidance and motility during both early abstinence (0–5 min post-METH exposure) and later abstinence (15–20 min post-METH exposure). Light avoidance was enhanced during early METH abstinence whereas motility was reduced during later abstinence. RAP-103 (0.01, 0.1, 1 μM), administered during METH abstinence, counteracted METH-induced light avoidance but did not rescue METH-induced motility deficits. Our results with planarians show that RAP-103 displays anxiolytic-like and motor-enhancing effects and counteracts METH abstinence-induced behaviors, highlighting the potential of RAP-103 as a chemokine-based CNS therapeutic.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115155"},"PeriodicalIF":2.5,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.physbeh.2025.115045
Yifan Zhao, Chengshi Li, Yibo Jiang, Hongge Jia
The present study employed eye-tracking technology and a free-viewing paradigm to explore the mechanisms of attentional bias toward emotional faces in individuals with social anxiety, using real and cartoon faces (angry, happy, disgusted, neutral) as stimuli. In Experiment 1, socially anxious individuals demonstrated significantly reduced total fixation duration and count on the eye regions of all four emotional face types presented by real people compared to controls. They also showed shorter fixation durations and fewer fixations on the facial area associated with disgust for real faces. In Experiment 2, both groups had longer total fixation duration and higher fixation counts on happy and neutral faces than on angry and disgusted faces. The findings suggest that attentional avoidance in socially anxious individuals is pronounced for the eye regions of real emotional faces, including positive ones, but not for cartoon faces. This indicates that attentional bias in social anxiety is influenced by both emotional and non-emotional social information in faces.
{"title":"Eyes tell all: Dissecting attentional bias in social anxiety through emotional faces.","authors":"Yifan Zhao, Chengshi Li, Yibo Jiang, Hongge Jia","doi":"10.1016/j.physbeh.2025.115045","DOIUrl":"10.1016/j.physbeh.2025.115045","url":null,"abstract":"<p><p>The present study employed eye-tracking technology and a free-viewing paradigm to explore the mechanisms of attentional bias toward emotional faces in individuals with social anxiety, using real and cartoon faces (angry, happy, disgusted, neutral) as stimuli. In Experiment 1, socially anxious individuals demonstrated significantly reduced total fixation duration and count on the eye regions of all four emotional face types presented by real people compared to controls. They also showed shorter fixation durations and fewer fixations on the facial area associated with disgust for real faces. In Experiment 2, both groups had longer total fixation duration and higher fixation counts on happy and neutral faces than on angry and disgusted faces. The findings suggest that attentional avoidance in socially anxious individuals is pronounced for the eye regions of real emotional faces, including positive ones, but not for cartoon faces. This indicates that attentional bias in social anxiety is influenced by both emotional and non-emotional social information in faces.</p>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":" ","pages":"115045"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.physbeh.2025.115058
Daniellen Cristhine Castro Alves, Leandro Vaz Toffoli, Wyllian Rafael Silva, Viviane Batista Estrada, Luiz Fernando Veríssimo, Ana Paula Franco Punhagui, Rafaela Pires Erthal, Maria Vitória Oliveira Miguel, Marcus Vinicius de Matos Gomes, Glaura Scantamburlo Alves Fernandes, Gislaine Garcia Pelosi
Recent evidence indicates the involvement of epigenetic mechanisms in the adaptive biological responses to chronic restraint stress. However, the impact of stress on the epigenetic programming of germ cells and subsequent effects on reproductive capacity remain understudied. Therefore, this study aimed to evaluate the effects of chronic restraint stress in sperm global DNA methylation and male reproductive function in Wistar rats. The animals were separated into two groups: the chronic restraint stress group (14 sessions) and the control group. After the final stress session, tissues of all the animals were collected for analysis. The stress group exhibited global sperm DNA hypermethylation (p = 0.0095), reduced sperm motility (p = 0.0079), increased sperm abnormalities (p = 0.0159), increased abnormal seminiferous tubules (p = 0.0159), and histopathological abnormalities in the epididymis. In addition, chronic restraint stress induced epididymal tissue reorganization in the caput region, and altered spermatogenic stages. There was a reduction of relative empty vesicle weight (p = 0.0317) and prostate (p = 0.0079). Sperm counts were decreased in the testis (p = 0.0317), in the caput /corpus of the epididymis (p = 0.0285) and cauda (p = 0.0159). These findings suggest that chronic stress can adversely affect male reproductive parameters, suggesting a vulnerability in the epigenetic programming of sperm to stress.
{"title":"Chronic restraint stress associations with sperm global DNA hypermethylation: Impacts on male reproductive function in rats.","authors":"Daniellen Cristhine Castro Alves, Leandro Vaz Toffoli, Wyllian Rafael Silva, Viviane Batista Estrada, Luiz Fernando Veríssimo, Ana Paula Franco Punhagui, Rafaela Pires Erthal, Maria Vitória Oliveira Miguel, Marcus Vinicius de Matos Gomes, Glaura Scantamburlo Alves Fernandes, Gislaine Garcia Pelosi","doi":"10.1016/j.physbeh.2025.115058","DOIUrl":"10.1016/j.physbeh.2025.115058","url":null,"abstract":"<p><p>Recent evidence indicates the involvement of epigenetic mechanisms in the adaptive biological responses to chronic restraint stress. However, the impact of stress on the epigenetic programming of germ cells and subsequent effects on reproductive capacity remain understudied. Therefore, this study aimed to evaluate the effects of chronic restraint stress in sperm global DNA methylation and male reproductive function in Wistar rats. The animals were separated into two groups: the chronic restraint stress group (14 sessions) and the control group. After the final stress session, tissues of all the animals were collected for analysis. The stress group exhibited global sperm DNA hypermethylation (p = 0.0095), reduced sperm motility (p = 0.0079), increased sperm abnormalities (p = 0.0159), increased abnormal seminiferous tubules (p = 0.0159), and histopathological abnormalities in the epididymis. In addition, chronic restraint stress induced epididymal tissue reorganization in the caput region, and altered spermatogenic stages. There was a reduction of relative empty vesicle weight (p = 0.0317) and prostate (p = 0.0079). Sperm counts were decreased in the testis (p = 0.0317), in the caput /corpus of the epididymis (p = 0.0285) and cauda (p = 0.0159). These findings suggest that chronic stress can adversely affect male reproductive parameters, suggesting a vulnerability in the epigenetic programming of sperm to stress.</p>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":" ","pages":"115058"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.physbeh.2025.115154
Zhuoran You , Meng Li , Jingyu Zeng , Jianguo Li , Simin Yan , Muhammad Shahzad Aslam , Junliang Shen , Siyu Liu , Jingxuan Li , Hui Fang , Lianlian Ning , Yanglin Ruan , Chongyao Hao , Xianjun Meng
Background
Acupuncture is a common complementary treatment for anxiety and depression. This study aimed to investigate whether acupuncture at Shangxing (GV23) and Fengfu (GV16) alleviates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in rats, and to explore the underlying mechanisms involving the Wnt/β-catenin signaling pathway.
Method
Male Sprague-Dawley rats were randomly assigned to five experimental groups: control group (CON), model group (CUMS), fluoxetine group (CUMS + FLX), acupuncture group (CUMS + AP), and sham acupuncture group (CUMS + SAP). Behavioral evaluations of depression-like symptoms were conducted using the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and elevated plus maze (EPM). Hippocampal morphology was assessed using hematoxylin–eosin (H&E) and Nissl staining. Ki67 and doublecortin (DCX) expression were detected by immunofluorescence. Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to quantify the expression levels of Wnt3a, glycogen synthase kinase 3β (GSK-3β), β-catenin in the hippocampus.
Result
Our findings indicated that CUMS induced depression-like behaviors, characterized by decreased sucrose preference, reduced locomotion and exploratory activity, less time spent in open arms, and prolonged immobility duration. Furthermore, compared to the CON group, the expression of Wnt3a, Dishevelled-2 (DVL2), β-catenin, the p-GSK-3β to GSK-3β ratio, positive cells of Ki67 and DCX were decreased but GSK-3β was increased in CUMS group. However, the detrimental effects were ameliorated by treatment with fluoxetine and acupuncture.
Conclusion
Acupuncture at GV23 and GV16 significantly improved depression in CUMS-induced rats by enhancing hippocampal neurogenesis and regulating the Wnt/β-catenin pathway.
{"title":"Acupuncture promotes antidepressant effects by enhancing hippocampal neurogenesis via Wnt/β-catenin signaling in a chronic unpredictable mild stress-induced rat depression model","authors":"Zhuoran You , Meng Li , Jingyu Zeng , Jianguo Li , Simin Yan , Muhammad Shahzad Aslam , Junliang Shen , Siyu Liu , Jingxuan Li , Hui Fang , Lianlian Ning , Yanglin Ruan , Chongyao Hao , Xianjun Meng","doi":"10.1016/j.physbeh.2025.115154","DOIUrl":"10.1016/j.physbeh.2025.115154","url":null,"abstract":"<div><h3>Background</h3><div>Acupuncture is a common complementary treatment for anxiety and depression. This study aimed to investigate whether acupuncture at <em>Shangxing</em> (GV23) and <em>Fengfu</em> (GV16) alleviates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in rats, and to explore the underlying mechanisms involving the Wnt/β-catenin signaling pathway.</div></div><div><h3>Method</h3><div>Male Sprague-Dawley rats were randomly assigned to five experimental groups: control group (CON), model group (CUMS), fluoxetine group (CUMS + FLX), acupuncture group (CUMS + AP), and sham acupuncture group (CUMS + SAP). Behavioral evaluations of depression-like symptoms were conducted using the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and elevated plus maze (EPM). Hippocampal morphology was assessed using hematoxylin–eosin (H&E) and Nissl staining. Ki67 and doublecortin (DCX) expression were detected by immunofluorescence. Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to quantify the expression levels of Wnt3a, glycogen synthase kinase 3β (GSK-3β), β-catenin in the hippocampus.</div></div><div><h3>Result</h3><div>Our findings indicated that CUMS induced depression-like behaviors, characterized by decreased sucrose preference, reduced locomotion and exploratory activity, less time spent in open arms, and prolonged immobility duration. Furthermore, compared to the CON group, the expression of Wnt3a, Dishevelled-2 (DVL2), β-catenin, the p-GSK-3β to GSK-3β ratio, positive cells of Ki67 and DCX were decreased but GSK-3β was increased in CUMS group. However, the detrimental effects were ameliorated by treatment with fluoxetine and acupuncture.</div></div><div><h3>Conclusion</h3><div>Acupuncture at GV23 and GV16 significantly improved depression in CUMS-induced rats by enhancing hippocampal neurogenesis and regulating the Wnt/β-catenin pathway.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115154"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-25DOI: 10.1016/j.physbeh.2025.115037
Mary Elizabeth Baugh, Monica L Ahrens, Amber K Burns, Rhianna M Sullivan, Abigail N Valle, Alexandra L Hanlon, Alexandra G DiFeliceantonio
The modern food landscape, marked by a rising prevalence of highly refined, ultra-processed, and highly palatable foods, combined with genetic and environmental susceptibilities, is widely considered a key factor driving obesity at the population level. Gaining insight into the physiological and behavioral mechanisms that shape food preferences and choices is crucial for understanding obesity's development and informing prevention strategies. One factor influencing habitual eating patterns, which may impact body weight, is flavor-nutrient learning. Research suggests that post-oral signaling is diminished in both animals and humans with obesity, potentially affecting flavor-nutrient learning. By analyzing pooled data from two similar preliminary studies, we found that markers of glycemic control-specifically fasting glucose and HbA1C-rather than BMI, were negatively correlated with changes in flavor liking in our flavor-nutrient learning task. These findings contribute to the expanding body of research on flavor-nutrient learning and underscore the variability in individual responses to these paradigms. Obesity is increasingly recognized as a complex and heterogeneous condition with diverse underlying mechanisms. Together, our findings and existing evidence emphasize the importance of further investigating how phenotypic factors interact to shape food preferences and eating behaviors.
{"title":"Metrics of glycemic control but not body weight influence flavor nutrient conditioning in humans.","authors":"Mary Elizabeth Baugh, Monica L Ahrens, Amber K Burns, Rhianna M Sullivan, Abigail N Valle, Alexandra L Hanlon, Alexandra G DiFeliceantonio","doi":"10.1016/j.physbeh.2025.115037","DOIUrl":"10.1016/j.physbeh.2025.115037","url":null,"abstract":"<p><p>The modern food landscape, marked by a rising prevalence of highly refined, ultra-processed, and highly palatable foods, combined with genetic and environmental susceptibilities, is widely considered a key factor driving obesity at the population level. Gaining insight into the physiological and behavioral mechanisms that shape food preferences and choices is crucial for understanding obesity's development and informing prevention strategies. One factor influencing habitual eating patterns, which may impact body weight, is flavor-nutrient learning. Research suggests that post-oral signaling is diminished in both animals and humans with obesity, potentially affecting flavor-nutrient learning. By analyzing pooled data from two similar preliminary studies, we found that markers of glycemic control-specifically fasting glucose and HbA1C-rather than BMI, were negatively correlated with changes in flavor liking in our flavor-nutrient learning task. These findings contribute to the expanding body of research on flavor-nutrient learning and underscore the variability in individual responses to these paradigms. Obesity is increasingly recognized as a complex and heterogeneous condition with diverse underlying mechanisms. Together, our findings and existing evidence emphasize the importance of further investigating how phenotypic factors interact to shape food preferences and eating behaviors.</p>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":" ","pages":"115037"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.physbeh.2025.115153
Rayran Walter Ramos de Sousa , Ingredy Lopes dos Santos , Débora Caroline do Nascimento Rodrigues , Maria Luísa Lima Barreto do Nascimento , Micaely Lorrana Pereira Conceição , Milena Monteiro de Freitas , Gabriel da Silva Fernandes , Rita de Cássia de Lima Sousa , Railson Pereira Souza , Irislene Costa Pereira , Francisco Leonardo Torres-Leal , Luciano da Silva Lopes , Paulo Michel Pinheiro Ferreira
Cancer has been correlated with psychiatrical disorders, and incidence of depression is about 3-fold higher in oncological patients. However, there is no validated animal models currently describing sarcoma-associated depression. Herein, we evaluated a preclinical way for estimating behavioral depression-like parameters in Sarcoma-180180180-transplanted mice and investigated the therapeutic efficacy of current clinical antidepressants. Firstly, S-180-bearing Swiss were evaluated using behavioral tests between days 10–11 after S-180 transplantation: open field (OFT), elevated plus maze (EPM), light–dark box (LDB), tail suspension (TST), forced swim (FST), and sucrose preference (SPT). Next, studies investigated effects of amitriptyline (AMI, oral), fluoxetine (FLU, oral), or 5-fluorouracil (5-FU, i.p.) at 10 or 20 mg/kg/day (alone or in combination) on behavior and oxidative/nitrosative profile of subacute-treated mice. No significant differences (p> 0.05) were observed about locomotor and exploratory activity (OFT, EPM, LDB). Meanwhile, S-180-bearing mice showed increase of immobility time (TST) and reduced sucrose preference in comparison with healthy animals (p< 0.05), typical features of depressive phenotype without alterations in anxiety-related parameters. These findings were associated with oxidative stress (malondialdehyde increasing) and antioxidant markers (superoxide dismutase decreasing/increasing) in the prefrontal cortex and/or hippocampus (p< 0.05). Such biochemical changes and depressive phenotype were partly attenuated by amitriptyline and fluoxetine 10 or 20 mg/kg/day for 10 days, but co-treatment with 5-FU did not show additional improvements. This physiopathological study represent a promising discovery highlighting the potential of non-clinical protocols to understand mesenchymal tumor-related depression and to develop new pharmacological tools against the multivariate spectrum of cancer-related diseases.
{"title":"Behavioral standardization and validation of a new model of cancer-induced depression in sarcoma-bearing mice","authors":"Rayran Walter Ramos de Sousa , Ingredy Lopes dos Santos , Débora Caroline do Nascimento Rodrigues , Maria Luísa Lima Barreto do Nascimento , Micaely Lorrana Pereira Conceição , Milena Monteiro de Freitas , Gabriel da Silva Fernandes , Rita de Cássia de Lima Sousa , Railson Pereira Souza , Irislene Costa Pereira , Francisco Leonardo Torres-Leal , Luciano da Silva Lopes , Paulo Michel Pinheiro Ferreira","doi":"10.1016/j.physbeh.2025.115153","DOIUrl":"10.1016/j.physbeh.2025.115153","url":null,"abstract":"<div><div>Cancer has been correlated with psychiatrical disorders, and incidence of depression is about 3-fold higher in oncological patients. However, there is no validated animal models currently describing sarcoma-associated depression. Herein, we evaluated a preclinical way for estimating behavioral depression-like parameters in Sarcoma-180180180-transplanted mice and investigated the therapeutic efficacy of current clinical antidepressants. Firstly, S-180-bearing Swiss were evaluated using behavioral tests between days 10–11 after S-180 transplantation: open field (OFT), elevated plus maze (EPM), light–dark box (LDB), tail suspension (TST), forced swim (FST), and sucrose preference (SPT). Next, studies investigated effects of amitriptyline (AMI, oral), fluoxetine (FLU, oral), or 5-fluorouracil (5-FU, i.p.) at 10 or 20 mg/kg/day (alone or in combination) on behavior and oxidative/nitrosative profile of subacute-treated mice. No significant differences (<em>p</em>> 0.05) were observed about locomotor and exploratory activity (OFT, EPM, LDB). Meanwhile, S-180-bearing mice showed increase of immobility time (TST) and reduced sucrose preference in comparison with healthy animals (<em>p</em>< 0.05), typical features of depressive phenotype without alterations in anxiety-related parameters. These findings were associated with oxidative stress (malondialdehyde increasing) and antioxidant markers (superoxide dismutase decreasing/increasing) in the prefrontal cortex and/or hippocampus (<em>p</em>< 0.05). Such biochemical changes and depressive phenotype were partly attenuated by amitriptyline and fluoxetine 10 or 20 mg/kg/day for 10 days, but co-treatment with 5-FU did not show additional improvements. This physiopathological study represent a promising discovery highlighting the potential of non-clinical protocols to understand mesenchymal tumor-related depression and to develop new pharmacological tools against the multivariate spectrum of cancer-related diseases.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"304 ","pages":"Article 115153"},"PeriodicalIF":2.5,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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