Pub Date : 2024-11-14DOI: 10.1016/j.physbeh.2024.114748
Richard J. Bodnar , Alexander Castillo , Ion Carata , Yerachmiel Bochner , Joymin Sarker , Nareesa Rayman , Shania Narine , Rachel Pines , Brian Limbu , Anthony Sclafani
C57BL/6 (B6) mice learn to prefer glucose or sucrose to initially isopreferred or even more preferred nonnutritive sweeteners due to the postoral appetite stimulating (appetition) actions of glucose. Recent evidence indicates that specific duodenal neuropod cells transmit the glucose appetition signal to the brain via glutamatergic synaptic connections with vagal afferents. The present study found that intraperitoneal pretreatment with a glutamatergic receptor antagonist cocktail (kynurenic acid (KA)/D-2-amino-3-phosphonopentanoic acid (AP3)) in B6 mice did not block the expression of their learned preference for 8% glucose solution over an initially-preferred 0.1% sucralose + 0.1% saccharin solution. However, acquisition of the glucose preference was blocked by drug treatment during 1-h training sessions with the two sweeteners. Systemic KA/AP3 injections also did not block the expression of the learned preference for a 10.6% sucrose solution over a 0.6% sucralose solution. Drug effects on the acquisition of the sucrose preference were not determined because sucrose, unlike glucose conditioning, required 24-h training trials. The findings that the 1-h training regimen conditioned 8% glucose, but not 10.6% sucrose, preferences suggest that glucose has more potent appetition actions. This was confirmed by the finding that B6 mice learned to prefer 10.6% glucose to 10.6% sucrose after 1-h or 24-h training despite an initial strong sucrose preference. This action can be explained by 10.6% sucrose's digestion in the gut to glucose and fructose with only glucose activating the gut-brain appetition pathway.
{"title":"Role of glutamatergic signaling in the acquisition and expression of learned sugar preferences in C57BL/6 mice","authors":"Richard J. Bodnar , Alexander Castillo , Ion Carata , Yerachmiel Bochner , Joymin Sarker , Nareesa Rayman , Shania Narine , Rachel Pines , Brian Limbu , Anthony Sclafani","doi":"10.1016/j.physbeh.2024.114748","DOIUrl":"10.1016/j.physbeh.2024.114748","url":null,"abstract":"<div><div>C57BL/6 (B6) mice learn to prefer glucose or sucrose to initially isopreferred or even more preferred nonnutritive sweeteners due to the postoral appetite stimulating (appetition) actions of glucose. Recent evidence indicates that specific duodenal neuropod cells transmit the glucose appetition signal to the brain via glutamatergic synaptic connections with vagal afferents. The present study found that intraperitoneal pretreatment with a glutamatergic receptor antagonist cocktail (kynurenic acid (KA)/D-2-amino-3-phosphonopentanoic acid (AP3)) in B6 mice did not block the expression of their learned preference for 8% glucose solution over an initially-preferred 0.1% sucralose + 0.1% saccharin solution. However, acquisition of the glucose preference was blocked by drug treatment during 1-h training sessions with the two sweeteners. Systemic KA/AP3 injections also did not block the expression of the learned preference for a 10.6% sucrose solution over a 0.6% sucralose solution. Drug effects on the acquisition of the sucrose preference were not determined because sucrose, unlike glucose conditioning, required 24-h training trials. The findings that the 1-h training regimen conditioned 8% glucose, but not 10.6% sucrose, preferences suggest that glucose has more potent appetition actions. This was confirmed by the finding that B6 mice learned to prefer 10.6% glucose to 10.6% sucrose after 1-h or 24-h training despite an initial strong sucrose preference. This action can be explained by 10.6% sucrose's digestion in the gut to glucose and fructose with only glucose activating the gut-brain appetition pathway.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"290 ","pages":"Article 114748"},"PeriodicalIF":2.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639570","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 : 2024-11-14DOI: 10.1016/j.physbeh.2024.114749
E. Leslie Cameron , Richard L. Doty
The mathematical relationship between the ability to detect an odorant and its concentration appears for some odorants to be non-monotonic, with reversals (“notches”) in performance appearing at points along the psychometric function. Like visual adaptation curves that reflect the differential sensitivities of cones and rods, such reversals may provide information about underlying olfactory receptor processes. However, the presence of such reversals is rarely acknowledged, few participants and odorants have been tested, and methodological concerns abound. In this study, we examined in detail the psychometric function for the odorant α-ionone using a sizable number of young participants and 10 log-based concentrations of α-ionone presented in a random fashion. A trial consisted of the counterbalanced presentation of an odorless mineral oil and a concentration of α-ionone in rapid succession using Snap & Sniff® wands. The participants reported which of the two seemed stronger and indicated their confidence on a 9-point scale. In Study 1, 24 participants completed a single 30-minute test session of 60 trials. In Study 2, 600 trials were obtained from each of nine participants over the course of ten 30-minute sessions. In both studies, notches were consistently found in the psychometric function near the 10−5 and 10−3.5 vol/vol concentrations. Participants’ trial-by-trial confidence judgments corresponded with their detection performance, but their self-rated sense of smell did not. This research definitively demonstrates the presence of reliable reversals in the human α-ionone psychometric function and begs the question as to whether such reversals reflect the recruitment of receptive elements with differing response profiles.
{"title":"Non-monotonic psychometric functions for α-ionone in young adults","authors":"E. Leslie Cameron , Richard L. Doty","doi":"10.1016/j.physbeh.2024.114749","DOIUrl":"10.1016/j.physbeh.2024.114749","url":null,"abstract":"<div><div>The mathematical relationship between the ability to detect an odorant and its concentration appears for some odorants to be non-monotonic, with reversals (“notches”) in performance appearing at points along the psychometric function. Like visual adaptation curves that reflect the differential sensitivities of cones and rods, such reversals may provide information about underlying olfactory receptor processes. However, the presence of such reversals is rarely acknowledged, few participants and odorants have been tested, and methodological concerns abound. In this study, we examined in detail the psychometric function for the odorant α-ionone using a sizable number of young participants and 10 log-based concentrations of α-ionone presented in a random fashion. A trial consisted of the counterbalanced presentation of an odorless mineral oil and a concentration of α-ionone in rapid succession using Snap & Sniff® wands. The participants reported which of the two seemed stronger and indicated their confidence on a 9-point scale. In Study 1, 24 participants completed a single 30-minute test session of 60 trials. In Study 2, 600 trials were obtained from each of nine participants over the course of ten 30-minute sessions. In both studies, notches were consistently found in the psychometric function near the 10<sup>−5</sup> and 10<sup>−3.5</sup> vol/vol concentrations. Participants’ trial-by-trial confidence judgments corresponded with their detection performance, but their self-rated sense of smell did not. This research definitively demonstrates the presence of reliable reversals in the human α-ionone psychometric function and begs the question as to whether such reversals reflect the recruitment of receptive elements with differing response profiles.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"290 ","pages":"Article 114749"},"PeriodicalIF":2.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644484","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 : 2024-11-14DOI: 10.1016/j.physbeh.2024.114734
Alexis R. Katz , Margaret P. Huntwork , Jay K. Kolls , Jenny L. Hewes , Calder R. Ellsworth , Robert D.E. Clark , John C. Carlson
Patients with natural killer (NK) cell deficiency or dysfunction are more susceptible to infections by Herpesviridae viruses, herpesvirus-related cancers, and macrophage activation syndromes. This review summarizes research on NK cell dysfunction following psychological stress, focusing on stressor type, duration, age of exposure, and species studied. Psychological stressors negatively affect NK cell activity (NKCA) across species. Prolonged stress leads to more significant decreases in NK cell number and function, with rehabilitation efforts proving ineffective in reversing these effects. Early life and prolonged stress exposure particularly increases the risk of infections and cancer due to impaired NKCA. The review also highlights that stress impacts males and females differently, with females exhibiting a more immunosuppressed NK cell phenotype. Notably, mice respond differently compared to humans and other animals, making them unsuitable for NK cell stress-related studies. Most studies measured NKCA using cytolytic assays against K-562 or YAC-1 cells. Although the exact mechanisms of NK cell dysfunction under stress remain unclear, potential causes include reduced release of secretory lysosomes with perforin or granzyme, impaired NK cell synapse formation, decreased expression of synapse-related molecules like CD2 or LFA-1 (CD11a), altered activating receptor expression, and dysregulated signaling pathways, such as decreased Erk1/2 phosphorylation and NFkB signaling.
These mechanisms are not mutually exclusive, and future research is needed to clarify these pathways and develop therapeutic interventions for stress-induced immune dysregulation.
自然杀伤细胞(NK)缺乏或功能障碍患者更容易受到疱疹病毒感染、疱疹病毒相关癌症和巨噬细胞活化综合征的影响。本综述总结了有关心理应激后 NK 细胞功能障碍的研究,重点关注应激源类型、持续时间、暴露年龄和研究物种。心理应激会对不同物种的 NK 细胞活性(NKCA)产生负面影响。长期的压力会导致 NK 细胞数量和功能的显著下降,而康复努力被证明无法有效逆转这些影响。由于 NKCA 功能受损,生命早期和长期的压力暴露尤其会增加感染和癌症的风险。综述还强调,压力对雄性和雌性的影响不同,雌性表现出更多的免疫抑制 NK 细胞表型。值得注意的是,小鼠的反应与人类和其他动物不同,因此不适合进行 NK 细胞应激相关研究。大多数研究使用针对 K-562 或 YAC-1 细胞的细胞溶解试验来测量 NKCA。虽然应激状态下 NK 细胞功能障碍的确切机制仍不清楚,但潜在的原因包括释放穿孔素或颗粒酶的分泌溶酶体减少、NK 细胞突触形成受损、CD2 或 LFA-1 (CD11a) 等突触相关分子表达减少、活化受体表达改变以及信号通路失调,如 Erk1/2 磷酸化和 NFkB 信号减少。这些机制并不相互排斥,未来的研究需要明确这些途径,并开发出针对应激诱导的免疫失调的治疗干预措施。
{"title":"Impact of psychological stressors on natural killer cell function: A comprehensive analysis based on stressor type, duration, intensity, and species","authors":"Alexis R. Katz , Margaret P. Huntwork , Jay K. Kolls , Jenny L. Hewes , Calder R. Ellsworth , Robert D.E. Clark , John C. Carlson","doi":"10.1016/j.physbeh.2024.114734","DOIUrl":"10.1016/j.physbeh.2024.114734","url":null,"abstract":"<div><div>Patients with natural killer (NK) cell deficiency or dysfunction are more susceptible to infections by Herpesviridae viruses, herpesvirus-related cancers, and macrophage activation syndromes. This review summarizes research on NK cell dysfunction following psychological stress, focusing on stressor type, duration, age of exposure, and species studied. Psychological stressors negatively affect NK cell activity (NKCA) across species. Prolonged stress leads to more significant decreases in NK cell number and function, with rehabilitation efforts proving ineffective in reversing these effects. Early life and prolonged stress exposure particularly increases the risk of infections and cancer due to impaired NKCA. The review also highlights that stress impacts males and females differently, with females exhibiting a more immunosuppressed NK cell phenotype. Notably, mice respond differently compared to humans and other animals, making them unsuitable for NK cell stress-related studies. Most studies measured NKCA using cytolytic assays against K-562 or YAC-1 cells. Although the exact mechanisms of NK cell dysfunction under stress remain unclear, potential causes include reduced release of secretory lysosomes with perforin or granzyme, impaired NK cell synapse formation, decreased expression of synapse-related molecules like CD2 or LFA-1 (CD11a), altered activating receptor expression, and dysregulated signaling pathways, such as decreased Erk1/2 phosphorylation and NFkB signaling.</div><div>These mechanisms are not mutually exclusive, and future research is needed to clarify these pathways and develop therapeutic interventions for stress-induced immune dysregulation.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"288 ","pages":"Article 114734"},"PeriodicalIF":2.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639569","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}
The implementation of conditions that favor optimum swimming activity (e.g., suitable flow regimes), has been associated with enhanced growth and improved welfare in some farmed fish species. Despite the importance of European seabass in aquaculture, the potential beneficial effects of rearing flow conditions have not been sufficiently explored in this species. This study investigates how the application of fast (F, 0.01–0.20 m s-1) or slow (S, <0.01 m s-1) steady flows in rearing tanks for 75-77 days affected physiological and behavioral traits in seabass fingerlings. Growth performance, external and internal morphology, and several physiological variables, including hematocrit, plasma cortisol concentration, and osmotic and ionic balance were not affected by flow conditions during rearing. Also, behavioral tests implemented in groups or isolated individuals suggest that coping styles were not affected by the two tank-rearing conditions. On the contrary, the swimming behavior assessed in tests was modified by the flow condition experienced during rearing. Mean swimming speed, peak acceleration, swimming distance, angular velocity, and meander showed some variability across different tests and time, although consistently displaying higher values in seabass reared in the F condition, suggesting increased activity and more consistent swimming patterns in that group. However, the cumulative time in proximity between individuals measured in behavioral group tests suggested that group cohesion was variable, without displaying differences between F and S groups. These findings have particularly important implications for fish welfare and may suggest plasticity in the behavioral response to rearing conditions for this species, although not affecting the assignment of the individuals to the different coping styles.
Summary statement
We investigated how mild current enrichment applied during early rearing in seabass modifies physiological and behavioral responses involving swimming activity, exploring the potential associations to fish welfare.
实施有利于最佳游泳活动的条件(如合适的水流制度)与一些养殖鱼类的生长和福利改善有关。尽管欧洲鲈鱼在水产养殖中很重要,但对该鱼种饲养水流条件的潜在有益影响还没有进行充分的探讨。本研究调查了在饲养箱中应用快速(F,0.01-0.20 m s-1)或慢速(S,-1)稳定水流 75-77 天对鲈鱼幼苗的生理和行为特征有何影响。生长性能、外部和内部形态以及一些生理变量(包括血细胞比容、血浆皮质醇浓度、渗透压和离子平衡)在饲养期间不受水流条件的影响。此外,在群体或单独个体中进行的行为测试表明,应对方式不受两种水槽饲养条件的影响。相反,在测试中评估的游泳行为受到饲养期间水流条件的影响。平均游泳速度、峰值加速度、游泳距离、角速度和蜿蜒度在不同的测试和时间中表现出一定的差异性,但在 F 条件下饲养的海鱼的数值一直较高,这表明该组海鱼的活动量增加,游泳模式也更加一致。然而,在行为群体测试中测量的个体之间的累积接近时间表明,群体凝聚力是可变的,F 组和 S 组之间没有差异。这些发现对鱼类福利具有特别重要的意义,并可能表明该物种对饲养条件的行为反应具有可塑性,尽管不会影响个体在不同应对方式下的分配。摘要说明:我们研究了在鲈鱼早期饲养期间应用温和的水流富集如何改变涉及游泳活动的生理和行为反应,并探讨了与鱼类福利的潜在关联。
{"title":"Early rearing of European seabass (Dicentrarchus labrax) with mild current enrichment modifies fish swimming behavior without altering their growth performance","authors":"Leonardo J. Magnoni , Xavier Cousin , Isabelle Leguen , Carlos Espirito-Santo , Frédéric Clota , Stéphane Lallement , Marie-Laure Bégout","doi":"10.1016/j.physbeh.2024.114742","DOIUrl":"10.1016/j.physbeh.2024.114742","url":null,"abstract":"<div><div>The implementation of conditions that favor optimum swimming activity (e.g., suitable flow regimes), has been associated with enhanced growth and improved welfare in some farmed fish species. Despite the importance of European seabass in aquaculture, the potential beneficial effects of rearing flow conditions have not been sufficiently explored in this species. This study investigates how the application of fast (F, 0.01–0.20 m s<sup>-1</sup>) or slow (S, <0.01 m s<sup>-1</sup>) steady flows in rearing tanks for 75-77 days affected physiological and behavioral traits in seabass fingerlings. Growth performance, external and internal morphology, and several physiological variables, including hematocrit, plasma cortisol concentration, and osmotic and ionic balance were not affected by flow conditions during rearing. Also, behavioral tests implemented in groups or isolated individuals suggest that coping styles were not affected by the two tank-rearing conditions. On the contrary, the swimming behavior assessed in tests was modified by the flow condition experienced during rearing. Mean swimming speed, peak acceleration, swimming distance, angular velocity, and meander showed some variability across different tests and time, although consistently displaying higher values in seabass reared in the F condition, suggesting increased activity and more consistent swimming patterns in that group. However, the cumulative time in proximity between individuals measured in behavioral group tests suggested that group cohesion was variable, without displaying differences between F and S groups. These findings have particularly important implications for fish welfare and may suggest plasticity in the behavioral response to rearing conditions for this species, although not affecting the assignment of the individuals to the different coping styles.</div></div><div><h3>Summary statement</h3><div>We investigated how mild current enrichment applied during early rearing in seabass modifies physiological and behavioral responses involving swimming activity, exploring the potential associations to fish welfare.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"289 ","pages":"Article 114742"},"PeriodicalIF":2.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626671","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 : 2024-11-10DOI: 10.1016/j.physbeh.2024.114743
Lewis A. O'Connor , Thieza G. Melo , Anna V. Golubeva , Francisco Donoso , Caitriona Scaife , Jane A. English , Yvonne M. Nolan , Olivia F. O'Leary
Chronic stress significantly impacts both physical and mental wellbeing, increasing risk of cardiovascular disease, immune dysregulation, and psychiatric conditions such as depression and anxiety disorders. The plasma proteome is a valuable source of biomarkers of health and disease, but the limited number of studies exploring the potential of the plasma proteome as a biomarker for stress-related disorders underscores the importance of further investigation of the effects of chronic stress on the plasma proteome. The aim of this study was to examine the effect of a 5-week chronic psychosocial stress paradigm on the plasma proteome in mice and to determine if any affected proteins correlated with stress-induced changes in behaviour and physiology, and thus might represent biomarkers of negative impacts of chronic stress. Using LC-MS/MS proteomic analysis, 38 proteins in the mouse plasma proteome were identified to be affected by chronic psychosocial stress. Functional analysis revealed that these proteins clustered into biological functions including inflammatory response, regulation of the immune response, complement and coagulation cascades, lipid metabolic process, and high-density lipoprotein particles. Correlation analyses of the identified proteins with stress-induced behavioral or physiological changes stress revealed significant correlations between stress-induced anxiety-like behaviour and Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Prosaposin, Actin-related protein 2/3 complex subunit 1B, Maltase-glucoamylase, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA and Fibrinogen-like protein 1. Chronic psychosocial stress blunted acute stress-induced corticosterone release, and this correlated with abundance of Pyrethroid hydrolase Ces2a; N-fatty-acyl-amino acid synthase/hydrolase Pm20d1, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA, Alpha-2-macroglobulin-P and L-selectin. Finally, stress-induced reductions in both brown and epididymal fat correlated with Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Kininogen-1, Apolipoprotein M, Angiopoietin-related protein 3, Proprotein convertase subtilisin/kexin type 9, and Lipopolysaccharide-binding protein. These findings demonstrate that chronic psychosocial stress induces alterations in plasma proteins implicated in key biological processes and pathways related to stress response, immune function, and lipid metabolic regulation. Further investigation into these proteins may provide new avenues for identification of biomarkers or mediators of stress-induced pathology.
慢性压力会严重影响身心健康,增加罹患心血管疾病、免疫失调以及抑郁症和焦虑症等精神疾病的风险。血浆蛋白质组是健康和疾病生物标志物的重要来源,但探索血浆蛋白质组作为压力相关疾病生物标志物潜力的研究数量有限,这突出了进一步研究慢性压力对血浆蛋白质组影响的重要性。本研究的目的是检测为期5周的慢性社会心理压力范式对小鼠血浆蛋白质组的影响,并确定是否有任何受影响的蛋白质与压力引起的行为和生理变化相关,从而可能代表慢性压力负面影响的生物标记物。通过LC-MS/MS蛋白质组分析,确定了小鼠血浆蛋白质组中受慢性社会心理压力影响的38种蛋白质。功能分析显示,这些蛋白质的生物功能包括炎症反应、免疫反应调节、补体和凝血级联、脂质代谢过程以及高密度脂蛋白颗粒、对已确定的蛋白质与应激诱导的行为或生理变化的相关性分析表明,应激诱导的焦虑样行为与磷脂酰肌醇-糖特异性磷脂酶 D 有显著的相关性、补体C2、表皮生长因子受体、前列腺素、肌动蛋白相关蛋白2/3复合体亚基1B、麦芽糖酶-葡聚糖酶、甘露寡糖1,2-α-甘露糖苷酶IA和纤维蛋白原样蛋白1。慢性社会心理应激会减弱急性应激诱导的皮质酮释放,这与拟除虫菊酯水解酶 Ces2a、N-脂肪酰氨基酸合成酶/水解酶 Pm20d1、甘露寡糖 1,2-α-甘露糖苷酶 IA、α-2-巨球蛋白-P 和 L-选择素的丰度相关。最后,压力诱导的棕色脂肪和附睾脂肪的减少与磷脂酰肌醇-糖特异性磷脂酶D、补体C2、表皮生长因子受体、激肽原-1、载脂蛋白M、血管生成素相关蛋白3、前蛋白转化酶subtilisin/kexin 9型和脂多糖结合蛋白有关。这些研究结果表明,慢性社会心理压力会诱导血浆蛋白的改变,而这些蛋白与压力反应、免疫功能和脂质代谢调节相关的关键生物过程和途径有牵连。对这些蛋白质的进一步研究可能会为确定压力诱导病理学的生物标志物或介质提供新的途径。
{"title":"Plasma proteomic signature of chronic psychosocial stress in mice","authors":"Lewis A. O'Connor , Thieza G. Melo , Anna V. Golubeva , Francisco Donoso , Caitriona Scaife , Jane A. English , Yvonne M. Nolan , Olivia F. O'Leary","doi":"10.1016/j.physbeh.2024.114743","DOIUrl":"10.1016/j.physbeh.2024.114743","url":null,"abstract":"<div><div>Chronic stress significantly impacts both physical and mental wellbeing, increasing risk of cardiovascular disease, immune dysregulation, and psychiatric conditions such as depression and anxiety disorders. The plasma proteome is a valuable source of biomarkers of health and disease, but the limited number of studies exploring the potential of the plasma proteome as a biomarker for stress-related disorders underscores the importance of further investigation of the effects of chronic stress on the plasma proteome. The aim of this study was to examine the effect of a 5-week chronic psychosocial stress paradigm on the plasma proteome in mice and to determine if any affected proteins correlated with stress-induced changes in behaviour and physiology, and thus might represent biomarkers of negative impacts of chronic stress. Using LC-MS/MS proteomic analysis, 38 proteins in the mouse plasma proteome were identified to be affected by chronic psychosocial stress. Functional analysis revealed that these proteins clustered into biological functions including inflammatory response, regulation of the immune response, complement and coagulation cascades, lipid metabolic process, and high-density lipoprotein particles. Correlation analyses of the identified proteins with stress-induced behavioral or physiological changes stress revealed significant correlations between stress-induced anxiety-like behaviour and Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Prosaposin, Actin-related protein 2/3 complex subunit 1B, Maltase-glucoamylase, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA and Fibrinogen-like protein 1. Chronic psychosocial stress blunted acute stress-induced corticosterone release, and this correlated with abundance of Pyrethroid hydrolase Ces2a; N-fatty-acyl-amino acid synthase/hydrolase Pm20d1, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA, Alpha-2-macroglobulin-P and L-selectin. Finally, stress-induced reductions in both brown and epididymal fat correlated with Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Kininogen-1, Apolipoprotein M, Angiopoietin-related protein 3, Proprotein convertase subtilisin/kexin type 9, and Lipopolysaccharide-binding protein. These findings demonstrate that chronic psychosocial stress induces alterations in plasma proteins implicated in key biological processes and pathways related to stress response, immune function, and lipid metabolic regulation. Further investigation into these proteins may provide new avenues for identification of biomarkers or mediators of stress-induced pathology.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"289 ","pages":"Article 114743"},"PeriodicalIF":2.4,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626676","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 : 2024-11-06DOI: 10.1016/j.physbeh.2024.114728
Joseph Knill-Jones , Gareth Shadwell , Howard T. Hurst , Chris Mawhinney , Jonathan K. Sinclair , Robert Allan
Purpose
Research regarding the effect cold-water immersion (CWI) has on cognitive performance often uses excessive cooling protocols (>1-hour) to measure the detrimental impact prolonged cold exposure has on cognition. Previous studies have not considered shorter CWI protocols, similar to that used in recovery and wellness practices (∼10 min).
Aims
To investigate a more ecologically valid CWI protocol on cognition, well-being and sleep in an acute and chronic manner. It was hypothesised that a therapeutic CWI protocol would improve well-being, and sleep and have no detrimental effect on cognition.
Methods
Thirteen healthy participants (20.85±2.15 years), (169.96±7.77 cm), (72.03±14.92 kg), (27.67±9.55 BF%) volunteered to complete a 4-week CWI protocol. Participants were immersed in cold water (10.42±0.59 °C) 3-times a week for 4-weeks. Cognitive performance (Stroop & TMT), well-being (WEMWBS, PSWQ, GAD-7, SHS) and sleep (PSQI) were measured acutely and chronically over the 4-week protocol along with thermoregulatory measures (Tsk, Tco, thermal comfort).
Results
Results show that CWI had no detrimental impact on cognitive performance, with Stroop performance & well-being seeing no differences acutely or chronically. Alternatively, the trail making test showed significant improvement from baseline (TMT-A 15.17±4.81-seconds, TMT-B 39.68±15.12-seconds) to week-3 (TMT-A 11.06±3.29-seconds, TMT-B 26.18±10.23-seconds). A reduction in sleep disturbances was seen from baseline scores of 7.85±3.44 AU to the end of week-3 measures 5.75±3.77 AU.
Conclusion
Therapeutic cooling can improve sleep quality when utilised in short frequent doses (3 times per week, for 4-weeks) and is not detrimental to cognitive performance, improving certain aspects of executive function.
{"title":"Influence of acute and chronic therapeutic cooling on cognitive performance and well-being","authors":"Joseph Knill-Jones , Gareth Shadwell , Howard T. Hurst , Chris Mawhinney , Jonathan K. Sinclair , Robert Allan","doi":"10.1016/j.physbeh.2024.114728","DOIUrl":"10.1016/j.physbeh.2024.114728","url":null,"abstract":"<div><h3>Purpose</h3><div>Research regarding the effect cold-water immersion (CWI) has on cognitive performance often uses excessive cooling protocols (>1-hour) to measure the detrimental impact prolonged cold exposure has on cognition. Previous studies have not considered shorter CWI protocols, similar to that used in recovery and wellness practices (∼10 min).</div></div><div><h3>Aims</h3><div>To investigate a more ecologically valid CWI protocol on cognition, well-being and sleep in an acute and chronic manner. It was hypothesised that a therapeutic CWI protocol would improve well-being, and sleep and have no detrimental effect on cognition.</div></div><div><h3>Methods</h3><div>Thirteen healthy participants (20.85±2.15 years), (169.96±7.77 cm), (72.03±14.92 kg), (27.67±9.55 BF%) volunteered to complete a 4-week CWI protocol. Participants were immersed in cold water (10.42±0.59 °C) 3-times a week for 4-weeks. Cognitive performance (Stroop & TMT), well-being (WEMWBS, PSWQ, GAD-7, SHS) and sleep (PSQI) were measured acutely and chronically over the 4-week protocol along with thermoregulatory measures (Tsk, Tco, thermal comfort).</div></div><div><h3>Results</h3><div>Results show that CWI had no detrimental impact on cognitive performance, with Stroop performance & well-being seeing no differences acutely or chronically. Alternatively, the trail making test showed significant improvement from baseline (TMT-A 15.17±4.81-seconds, TMT-B 39.68±15.12-seconds) to week-3 (TMT-A 11.06±3.29-seconds, TMT-B 26.18±10.23-seconds). A reduction in sleep disturbances was seen from baseline scores of 7.85±3.44 AU to the end of week-3 measures 5.75±3.77 AU.</div></div><div><h3>Conclusion</h3><div>Therapeutic cooling can improve sleep quality when utilised in short frequent doses (3 times per week, for 4-weeks) and is not detrimental to cognitive performance, improving certain aspects of executive function.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"289 ","pages":"Article 114728"},"PeriodicalIF":2.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626672","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 : 2024-11-05DOI: 10.1016/j.physbeh.2024.114729
Julie E. Finnell , Carrie R. Ferrario
Food restriction in rodents can increase circulating corticosterone, which reflects activation of physiological stress responses. These responses affect a myriad of behaviors and physiological processes and can increase the risk of obesity. Most studies in this area have used experimenter-imposed restriction. However, rats will voluntarily restrict their food intake if they are returned to chow after a period of access to sugary, fatty “junk food” (JF) diet. Here we examine the effects of voluntary food restriction in obesity-prone and -resistant male and female rats on circulating corticosterone concentrations and determine whether corticosterone release in response to acute stress differs in groups with a history of JF consumption.
{"title":"Voluntary food restriction does not affect circulating corticosterone in obesity-prone or -resistant male and female rats","authors":"Julie E. Finnell , Carrie R. Ferrario","doi":"10.1016/j.physbeh.2024.114729","DOIUrl":"10.1016/j.physbeh.2024.114729","url":null,"abstract":"<div><div>Food restriction in rodents can increase circulating corticosterone, which reflects activation of physiological stress responses. These responses affect a myriad of behaviors and physiological processes and can increase the risk of obesity. Most studies in this area have used experimenter-imposed restriction. However, rats will voluntarily restrict their food intake if they are returned to chow after a period of access to sugary, fatty “junk food” (JF) diet. Here we examine the effects of voluntary food restriction in obesity-prone and -resistant male and female rats on circulating corticosterone concentrations and determine whether corticosterone release in response to acute stress differs in groups with a history of JF consumption.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"288 ","pages":"Article 114729"},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605962","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 : 2024-11-05DOI: 10.1016/j.physbeh.2024.114733
Junyi Gan , Yin Wu , Xue Lei , Chengyang Han
Androsta-4,16‑dien-3-one (androstadienone, AND), a steroid predominantly found in male secretions, has been associated with a variety of sex-specific effects on emotion, physiological states, cognition, and neural activity. An expanding body of literature has explored the influence of AND on human behavior and perception, leading to its frequent description as a “putative human sex pheromone.” This article reviews the existing research on the physiological, cognitive, and neuroimaging effects of AND, critically assessing the evidence regarding its classification as a human sex pheromone. Additionally, it underscores the need for methodological standardization and rigor in future studies to establish clearer conclusions. Based on current evidence, the categorization of AND as a “human sex pheromone” remains inconclusive, highlighting the necessity for continued investigation. Future research directions are suggested to further elucidate AND's potential effects and applications.
雄甾-4,16-二烯-3-酮(androstadienone,AND)是一种主要存在于男性分泌物中的类固醇,它对情绪、生理状态、认知和神经活动具有多种性别特异性影响。越来越多的文献探讨了 AND 对人类行为和感知的影响,因此它经常被描述为 "推定的人类性信息素"。本文回顾了现有关于 AND 的生理、认知和神经影像学影响的研究,对将其归类为人类性信息素的证据进行了批判性评估。此外,文章还强调了未来研究中方法标准化和严谨性的必要性,以便得出更明确的结论。根据目前的证据,将 AND 归类为 "人类性信息素 "仍然没有定论,这凸显了继续研究的必要性。建议未来的研究方向是进一步阐明 AND 的潜在作用和应用。
{"title":"Is androstadienone a human male pheromone? More research is needed","authors":"Junyi Gan , Yin Wu , Xue Lei , Chengyang Han","doi":"10.1016/j.physbeh.2024.114733","DOIUrl":"10.1016/j.physbeh.2024.114733","url":null,"abstract":"<div><div>Androsta-4,16‑dien-3-one (androstadienone, AND), a steroid predominantly found in male secretions, has been associated with a variety of sex-specific effects on emotion, physiological states, cognition, and neural activity. An expanding body of literature has explored the influence of AND on human behavior and perception, leading to its frequent description as a “putative human sex pheromone.” This article reviews the existing research on the physiological, cognitive, and neuroimaging effects of AND, critically assessing the evidence regarding its classification as a human sex pheromone. Additionally, it underscores the need for methodological standardization and rigor in future studies to establish clearer conclusions. Based on current evidence, the categorization of AND as a “human sex pheromone” remains inconclusive, highlighting the necessity for continued investigation. Future research directions are suggested to further elucidate AND's potential effects and applications.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"288 ","pages":"Article 114733"},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605967","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 : 2024-11-05DOI: 10.1016/j.physbeh.2024.114731
Christakis Kagios , Susanne Hetty , Alfhild Grönbladh , Maria J Pereira , Jan W Eriksson , Erika Roman
This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square field™ (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (p < 0.001) and increased adipose tissue weight in comparison to the control (p < 0.001) and restricted (p < 0.001) groups. Glucose was significantly increased (p < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (p < 0.01; p < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (p < 0.01) and restricted (p < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (p < 0.001; p < 0.05) and restricted (p < 0.001; p < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development.
{"title":"Cafeteria diet and caloric restriction affect metabolic but not behavioral characteristics in male Wistar rats","authors":"Christakis Kagios , Susanne Hetty , Alfhild Grönbladh , Maria J Pereira , Jan W Eriksson , Erika Roman","doi":"10.1016/j.physbeh.2024.114731","DOIUrl":"10.1016/j.physbeh.2024.114731","url":null,"abstract":"<div><div>This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (<em>n</em> = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square field™ (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (<em>p</em> < 0.001) and increased adipose tissue weight in comparison to the control (<em>p</em> < 0.001) and restricted (<em>p</em> < 0.001) groups. Glucose was significantly increased (<em>p</em> < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (<em>p</em> < 0.01; <em>p</em> < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (<em>p</em> < 0.01) and restricted (<em>p</em> < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (<em>p</em> < 0.001; <em>p</em> < 0.05) and restricted (<em>p</em> < 0.001; <em>p</em> < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"288 ","pages":"Article 114731"},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590868","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 : 2024-11-05DOI: 10.1016/j.physbeh.2024.114732
Heba-Tallah Abd Elrahim Abd Elkader , Ahmed S. Al-Shami , Hanaa Said Darwish
Thyroid hormones are essential for brain development, and a shortage throughout the fetal and postnatal periods can result in mood disorders. Perinatal exposure to bisphenol A (BPA) affects thyroid activity and dependent processes indirectly during pregnancy or early postnatal life. This is particularly important because it may cause changes in tissue ontogeny, increasing the risk of developing disorders later in life. The study aimed to investigate the consequences of thyroid hormone deficiency on anxiety, social, and depressive behaviors, as well as disruption in thyroid peroxidase (TPO) gene expression, which influences the NF-κB/Nrf-2/HO-1/iNOS signaling pathway, leading to oxidative stress, inflammation, and DNA fragmentation in perinatal BPA exposure (PND18), and whether these effects can be observed in juvenile (PND60) and adult (PND95) male offspring rats. BPA increased anxiety-like behavior while decreasing sucrose preference and sociability on a choice task between novel conspecific male rats and enhanced immobility on the forced swim test. Perinatal exposure to BPA causes thyroid insult by overproducing ROS, increasing iNOS, and NF-κB levels—these effects, in turn, down-regulate Nrf-2/HO-1 signaling, resulting in DNA fragmentation within thyroid tissues. Furthermore, perinatal BPA exposure for 60 and 95 days resulted in a significant fold decrease in TPO mRNA levels in the thyroid tissues, with an insignificant fold rise in TPO expression levels in BPA 50–60. In conclusion, the present study found that perinatal BPA exposure induced thyroid allostasis-adaptive response by inhibiting the NF-κB/Nrf-2/HO-1/iNOS signaling pathway and altering the transcriptional expression of TPO, where TSH reinforced a possible association with TPO activity, disrupting thyroid hormone synthesis in juvenile rats and gradual deterioration reaching the adult stage.
甲状腺激素对大脑发育至关重要,在胎儿期和产后如果缺乏甲状腺激素,就会导致情绪失调。围产期暴露于双酚 A(BPA)会在孕期或产后早期间接影响甲状腺活动和依赖过程。这一点尤为重要,因为它可能会导致组织本体发生变化,从而增加日后罹患疾病的风险。本研究旨在调查甲状腺激素缺乏对焦虑、社交和抑郁行为的影响,以及甲状腺过氧化物酶(TPO)基因表达的干扰,TPO基因表达会影响NF-κB/Nrf-2/HO-1/iNOS信号通路,导致围产期(PND18)暴露于双酚A的雄性后代大鼠出现氧化应激、炎症和DNA碎片,以及这些影响是否会在幼年(PND60)和成年(PND95)雄性后代大鼠中观察到。双酚 A 会增加焦虑样行为,同时降低对蔗糖的偏好和在同种新雄性大鼠之间进行选择任务时的交际能力,并增强强迫游泳试验中的不稳定性。围产期暴露于双酚 A 会过度产生 ROS、增加 iNOS 和 NF-κB 水平,从而导致甲状腺损伤--这些效应反过来又会下调 Nrf-2/HO-1 信号,导致甲状腺组织内的 DNA 断裂。此外,围产期暴露双酚A 60天和95天会导致甲状腺组织中的TPO mRNA水平显著下降一倍,而双酚A 50-60天时TPO表达水平的上升一倍不明显。总之,本研究发现,围产期双酚A暴露通过抑制NF-κB/Nrf-2/HO-1/iNOS信号通路和改变TPO的转录表达,诱导甲状腺失稳-适应性反应,其中TSH与TPO活性可能有关联,从而破坏幼鼠的甲状腺激素合成,并在成年阶段逐渐恶化。
{"title":"Perinatal bisphenol A exposure has an age- and dose-dependent association with thyroid allostasis adaptive response, as well as anxiogenic-depressive-like and asocial behaviors in juvenile and adult male rats","authors":"Heba-Tallah Abd Elrahim Abd Elkader , Ahmed S. Al-Shami , Hanaa Said Darwish","doi":"10.1016/j.physbeh.2024.114732","DOIUrl":"10.1016/j.physbeh.2024.114732","url":null,"abstract":"<div><div>Thyroid hormones are essential for brain development, and a shortage throughout the fetal and postnatal periods can result in mood disorders. Perinatal exposure to bisphenol A (BPA) affects thyroid activity and dependent processes indirectly during pregnancy or early postnatal life. This is particularly important because it may cause changes in tissue ontogeny, increasing the risk of developing disorders later in life. The study aimed to investigate the consequences of thyroid hormone deficiency on anxiety, social, and depressive behaviors, as well as disruption in thyroid peroxidase (TPO) gene expression, which influences the NF-κB/Nrf-2/HO-1/iNOS signaling pathway, leading to oxidative stress, inflammation, and DNA fragmentation in perinatal BPA exposure (PND18), and whether these effects can be observed in juvenile (PND60) and adult (PND95) male offspring rats. BPA increased anxiety-like behavior while decreasing sucrose preference and sociability on a choice task between novel conspecific male rats and enhanced immobility on the forced swim test. Perinatal exposure to BPA causes thyroid insult by overproducing ROS, increasing iNOS, and NF-κB levels—these effects, in turn, down-regulate Nrf-2/HO-1 signaling, resulting in DNA fragmentation within thyroid tissues. Furthermore, perinatal BPA exposure for 60 and 95 days resulted in a significant fold decrease in TPO mRNA levels in the thyroid tissues, with an insignificant fold rise in TPO expression levels in BPA 50–60. In conclusion, the present study found that perinatal BPA exposure induced thyroid allostasis-adaptive response by inhibiting the NF-κB/Nrf-2/HO-1/iNOS signaling pathway and altering the transcriptional expression of TPO, where TSH reinforced a possible association with TPO activity, disrupting thyroid hormone synthesis in juvenile rats and gradual deterioration reaching the adult stage.</div></div>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":"288 ","pages":"Article 114732"},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605980","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}