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Neural mechanisms underlying cognitive impairment in depression and cognitive benefits of exercise intervention 抑郁症认知障碍的神经机制和运动干预对认知的益处。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-02 DOI: 10.1016/j.bbr.2024.115218
Huizi Tian , Zhifang Wang , Yao Meng , Lu Geng , Hao Lian , Zhifei Shi , Zhidong Zhuang , Wenpeng Cai , Mengyang He

Depression is associated with functional brain impairments, although comprehensive studies remain limited. This study reviews neural mechanisms underlying cognitive impairment in depression and identifies associated activation abnormalities in brain regions. The study also explores the underlying neural processes of cognitive benefits of exercise intervention for depression. Executive function impairments, including working memory, inhibitory control and cognitive flexibility are associated with frontal cortex and anterior cingulate areas, especially dorsolateral prefrontal cortex. Depression is associated with certain neural impairments of reward processing, especially orbitofrontal cortex, prefrontal cortex, nucleus accumbens and other striatal regions. Depressed patients exhibit decreased activity in the hippocampus during memory function. Physical exercise has been found to enhance memory function, executive function, and reward processing in depression patients by increasing functional brain regions and the brain-derived neurotrophic factor (BDNF) as a nutritional factor also plays a key role in exercise intervention. The study documents neurophysiological mechanisms behind exercise intervention's improved functions. In summary, the study provides insights into neural mechanisms underlying cognitive impairments in depression and the effectiveness of exercise as a treatment.

抑郁症与大脑功能障碍有关,但全面的研究仍然有限。本研究回顾了抑郁症认知障碍的神经机制,并确定了相关脑区的激活异常。研究还探讨了运动干预对抑郁症患者认知获益的潜在神经过程。包括工作记忆、抑制控制和认知灵活性在内的执行功能障碍与额叶皮层和前扣带回区域有关,尤其是背外侧前额叶皮层。抑郁症与奖赏处理的某些神经损伤有关,尤其是眶额皮质、前额皮质、伏隔核和其他纹状体区域。抑郁症患者的海马体在发挥记忆功能时活动减少。研究发现,体育锻炼可通过增加脑功能区来增强抑郁症患者的记忆功能、执行功能和奖赏处理能力,而作为营养因子的脑源性神经营养因子(BDNF)在锻炼干预中也发挥着关键作用。研究记录了运动干预改善功能背后的神经生理学机制。总之,这项研究深入揭示了抑郁症认知障碍的神经机制以及运动作为治疗手段的有效性。
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引用次数: 0
Blunted food conditioned place preference-like behavior in adolescent-stressed male hamsters 青春期应激雄性仓鼠的食物条件性场所偏好行为减弱
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-02 DOI: 10.1016/j.bbr.2024.115234
Kevin M. Moran, Leah Jarrell, Misheel Khashchuluun, Kurt R. Moran, Julia Rodriguez, Anna Tran, Yvon Delville

Social stress during adolescence results in long lasting weight gain, obesity, and enhanced food hoarding behavior in hamsters. We wanted to determine whether stress also enhanced conditioned place preference-like behavior (CPP-like) for food reward, as would be expected from studies with substances like cocaine. Our experimental animals were exposed daily to aggressive adults for two weeks in early puberty, while also trained to explore a V-shaped maze containing a food reward at one end. They were tested for CPP-like behavior on the last day of social stress. Our results showed that while stress enhanced weight gain, food intake, food efficiency, and body fat, it caused a reduction of Place Preference as compared to controls. In fact, the correlated relationship between Place Preference and body fat was inverted by stress exposure: while it was positively correlated in controls, it was mildly negatively correlated in stressed hamsters. These unexpected data illustrate the extent of adaptive behavior in foraging animals once a resource has become untrustworthy.

青春期的社会压力会导致仓鼠长期体重增加、肥胖和囤积食物行为增强。我们想确定压力是否也会增强对食物奖赏的条件性场所偏好行为(CPP-like),正如可卡因等物质的研究预期的那样。我们的实验动物在青春期早期每天接触具有攻击性的成年仓鼠两周,同时训练它们探索一个 V 形迷宫,迷宫的一端有食物奖励。在社会压力的最后一天,我们对它们进行了类似 CPP 行为的测试。我们的结果表明,与对照组相比,虽然压力会促进体重增加、食物摄入量、食物效率和体脂增加,但却会导致位置偏好降低。事实上,场所偏好与体脂之间的相关关系因压力暴露而颠倒:在对照组中呈正相关,而在压力仓鼠中则呈轻度负相关。这些出乎意料的数据说明,一旦资源变得不可信,觅食动物的适应行为程度会有多大。
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引用次数: 0
Cortical high-frequency oscillations (≈ 110 Hz) in cats are state-dependent and enhanced by a subanesthetic dose of ketamine 猫的皮层高频振荡(≈ 110Hz)具有状态依赖性,亚麻醉剂量的氯胺酮会增强这种振荡。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115231
Santiago Castro-Zaballa , Joaquín González , Matías Cavelli , Diego Mateos , Claudia Pascovich , Adriano Tort , Mark Jeremy Hunt , Pablo Torterolo

Ketamine is an NMDA receptor antagonist that has antidepressant and anesthetic properties. At subanesthetic doses, ketamine induces transient psychosis in humans, and is used to model psychosis in experimental animals. In rodents, subanesthetic doses of ketamine increase the power of high-frequency oscillations (HFO, > 100 Hz) in the electroencephalogram (EEG), a frequency band linked to cognitive functions. However, to date, the effects of ketamine in carnivores and primates have been poorly investigated. Here, we examined in the cat, cortical HFO during wakefulness, sleep, and after administering a sub-anesthetic dose of ketamine. Four cats were prepared with cortical electrodes for chronic polysomnographic recordings in head-restrained conditions. The cortical HFO power, connectivity, direction of the information flow using Granger Causality (GC) analysis, their relationships with respiratory activity, and the effect of auditory stimulation were analyzed. During wakefulness, but not during sleep, we found that HFO were coupled with the inspiratory phase of the respiration. After ketamine administration, HFO power was enhanced and remained associated with the inspiratory phase. GC analysis suggests that ketamine-enhanced HFO originate from the olfactory bulb (OB) and stream towards the prefrontal cortex (Pf). Accordingly, occluding the nostrils significantly reduced the power of the ketamine-enhanced HFO in both the OB and Pf. Finally, auditory stimulation did not affect HFO. In conclusion, the HFO are associated with respiration during wakefulness, but not during sleep. The enhancement of this rhythm by ketamine may disrupt cortical information processing, which could contribute to some of the neuropsychiatric effects associated with ketamine.

氯胺酮是一种 NMDA 受体拮抗剂,具有抗抑郁和麻醉特性。在亚麻醉剂量下,氯胺酮会诱发人类短暂性精神病,并被用于在实验动物中建立精神病模型。在啮齿类动物中,亚麻醉剂量的氯胺酮会增加脑电图(EEG)中高频振荡(HFO,> 100Hz)的功率,这一频段与认知功能有关。然而,迄今为止,氯胺酮对食肉动物和灵长类动物的影响还鲜有研究。在这里,我们研究了猫在清醒、睡眠和注射亚麻醉剂量氯胺酮后的皮层高频脑电图。我们为四只猫准备了皮质电极,以便在头部受限的条件下进行慢性多导睡眠图记录。研究人员利用格兰杰因果关系(GC)分析法分析了大脑皮层 HFO 功率、连接性、信息流方向、它们与呼吸活动的关系以及听觉刺激的影响。我们发现,在清醒状态下,而在睡眠状态下,HFO 与呼吸的吸气阶段相关联。服用氯胺酮后,HFO的功率增强,并保持与吸气相联系。GC 分析表明,氯胺酮增强的 HFO 源自嗅球(OB)并流向前额叶皮层(Pf)。因此,闭塞鼻孔可显著降低氯胺酮增强的 HFO 在嗅球和前额叶皮层的功率。最后,听觉刺激对 HFO 没有影响。总之,HFO与清醒时的呼吸有关,但与睡眠时无关。氯胺酮增强这种节律可能会扰乱大脑皮层的信息处理,从而导致氯胺酮的一些神经精神效应。
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引用次数: 0
Opioid-environment interaction: Contrasting effects of morphine administered in a novel versus familiar environment on acute and repeated morphine induced behavioral effects and on acute morphine ERK activation in reward associated brain areas 阿片类药物与环境的相互作用:在新环境和熟悉环境中施用吗啡对吗啡诱导的急性和重复行为效应以及吗啡ERK在奖赏相关脑区的急性激活效应的对比效应。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115221
Gabriela Corrêa Coelho , Luiz Gustavo Soares Carvalho Crespo , Maria de Fátima dos Santos Sampaio , Regina Claudia Barbosa Silva , Richard Ian Samuels , Robert J. Carey , Marinete Pinheiro Carrera

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction.

我们报告说,环境背景会对吗啡的运动行为和ERK效应产生重大影响。我们从环境新奇度/熟悉度的维度操纵了环境背景,并在急性和慢性吗啡治疗方案中测量了吗啡的行为效应。给 Wistar 大鼠(每组 7 只)注射吗啡 10 毫克/千克或吗啡载体(静脉注射),并立即将其放入竞技场中 5 分钟,然后在 1 天或 5 天后测量其运动活动。吗啡治疗要么在大鼠对环境感到陌生时开始,要么在大鼠通过每天在场内进行5次非药物测试熟悉场内环境后开始。结果表明,吗啡的急性和慢性作用会因环境是新奇的还是熟悉的而发生强烈变化。与在熟悉的环境中施用吗啡相比,在新环境中施用的急性吗啡能更大幅度地增加多个脑区的ERK活性,尤其是在与奖赏相关的区域,如VTA。在新奇环境中重复注射吗啡会诱导强烈的运动敏感化,而在熟悉环境中重复注射吗啡则不会诱导运动刺激效应,而是诱导药物分辨刺激的不习惯效应。环境的新颖性/熟悉性和持续的多巴胺活动对急性和慢性吗啡治疗的明显不同影响可能与阿片类药物成瘾有潜在的临床相关性。
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引用次数: 0
White matter correlates of cognition: A diffusion magnetic resonance imaging study 认知的白质相关性:扩散磁共振成像研究
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115222
Mohammadamin Parsaei , Gelayol Barahman , Parvaneh Hamian Roumiani , Ehsan Ranjbar , Sahar Ansari , Anahita Najafi , Hanie Karimi , Mohammad Hadi Aarabi , Hossein Sanjari Moghaddam

Background

Our comprehension of the interplay of cognition and the brain remains constrained. While functional imaging studies have identified cognitive brain regions, structural correlates of cognitive functions remain underexplored. Advanced methods like Diffusion Magnetic Resonance Imaging (DMRI) facilitate the exploration of brain connectivity and White Matter (WM) tract microstructure. Therefore, we conducted connectometry method on DMRI data, to reveal WM tracts associated with cognition.

Methods

125 healthy participants from the National Institute of Mental Health Intramural Healthy Volunteer Dataset were recruited. Multiple regression analyses were conducted between DMRI-derived Quantitative Anisotropy (QA) values within WM tracts and scores of participants in Flanker Inhibitory Control and Attention Test (attention), Dimensional Change Card Sort (executive function), Picture Sequence Memory Test (episodic memory), and List Sorting Working Memory Test (working memory) tasks from National Institute of Health toolbox. The significance level was set at False Discovery Rate (FDR)<0.05.

Results

We identified significant positive correlations between the QA of WM tracts within the left cerebellum and bilateral fornix with attention, executive functioning, and episodic memory (FDR=0.018, 0.0002, and 0.0002, respectively), and a negative correlation between QA of WM tracts within bilateral cerebellum with attention (FDR=0.028). Working memory demonstrated positive correlations with QA of left inferior longitudinal and left inferior fronto-occipital fasciculi (FDR=0.0009), while it showed a negative correlation with QA of right cerebellar tracts (FDR=0.0005).

Conclusion

Our results underscore the intricate link between cognitive performance and WM integrity in frontal, temporal, and cerebellar regions, offering insights into early detection and targeted interventions for cognitive disorders.

背景:我们对认知与大脑相互作用的理解仍然受到限制。虽然功能成像研究已经确定了认知脑区,但认知功能的结构相关性仍未得到充分探索。扩散磁共振成像(DMRI)等先进方法有助于探索大脑连接性和白质(WM)束微观结构。因此,我们对 DMRI 数据进行了连接测量法,以揭示与认知相关的白质束。在WM束内的DMRI衍生定量各向异性(QA)值与美国国家卫生研究院工具箱中的Flanker抑制控制和注意力测试(注意力)、维度变化卡片分类(执行功能)、图片序列记忆测试(外显记忆)和列表分类工作记忆测试(工作记忆)任务的得分之间进行了多元回归分析。显著性水平设定为假发现率(FDR):我们发现左侧小脑和双侧穹窿内WM束的QA与注意力、执行功能和外显记忆之间存在明显的正相关(FDR分别为0.018、0.0002和0.0002),而双侧小脑内WM束的QA与注意力之间存在负相关(FDR=0.028)。工作记忆与左下纵束和左下前枕束的QA呈正相关(FDR=0.0009),而与右侧小脑束的QA呈负相关(FDR=0.0005):我们的研究结果表明,认知能力与额叶、颞叶和小脑区域的WM完整性之间存在着错综复杂的联系,这为认知障碍的早期检测和有针对性的干预提供了启示。
{"title":"White matter correlates of cognition: A diffusion magnetic resonance imaging study","authors":"Mohammadamin Parsaei ,&nbsp;Gelayol Barahman ,&nbsp;Parvaneh Hamian Roumiani ,&nbsp;Ehsan Ranjbar ,&nbsp;Sahar Ansari ,&nbsp;Anahita Najafi ,&nbsp;Hanie Karimi ,&nbsp;Mohammad Hadi Aarabi ,&nbsp;Hossein Sanjari Moghaddam","doi":"10.1016/j.bbr.2024.115222","DOIUrl":"10.1016/j.bbr.2024.115222","url":null,"abstract":"<div><h3>Background</h3><p>Our comprehension of the interplay of cognition and the brain remains constrained. While functional imaging studies have identified cognitive brain regions, structural correlates of cognitive functions remain underexplored. Advanced methods like Diffusion Magnetic Resonance Imaging (DMRI) facilitate the exploration of brain connectivity and White Matter (WM) tract microstructure. Therefore, we conducted connectometry method on DMRI data, to reveal WM tracts associated with cognition.</p></div><div><h3>Methods</h3><p>125 healthy participants from the National Institute of Mental Health Intramural Healthy Volunteer Dataset were recruited. Multiple regression analyses were conducted between DMRI-derived Quantitative Anisotropy (QA) values within WM tracts and scores of participants in Flanker Inhibitory Control and Attention Test (attention), Dimensional Change Card Sort (executive function), Picture Sequence Memory Test (episodic memory), and List Sorting Working Memory Test (working memory) tasks from National Institute of Health toolbox. The significance level was set at False Discovery Rate (FDR)&lt;0.05.</p></div><div><h3>Results</h3><p>We identified significant positive correlations between the QA of WM tracts within the left cerebellum and bilateral fornix with attention, executive functioning, and episodic memory (FDR=0.018, 0.0002, and 0.0002, respectively), and a negative correlation between QA of WM tracts within bilateral cerebellum with attention (FDR=0.028). Working memory demonstrated positive correlations with QA of left inferior longitudinal and left inferior fronto-occipital fasciculi (FDR=0.0009), while it showed a negative correlation with QA of right cerebellar tracts (FDR=0.0005).</p></div><div><h3>Conclusion</h3><p>Our results underscore the intricate link between cognitive performance and WM integrity in frontal, temporal, and cerebellar regions, offering insights into early detection and targeted interventions for cognitive disorders.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"476 ","pages":"Article 115222"},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation 凯尼酸诱导的兴奋性脊髓损伤会损害运动能力、改变痛觉并减少 CREB 的核转位
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115219
Benjamín Zylberberg , Angela M. Suburo , M. Florencia Coronel , Graciela L. Mazzone

Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.

我们之前的体外研究表明,谷氨酸类似物凯恩酸盐(KA)诱发的兴奋毒性会显著减少大鼠脊髓神经元的数量,并引发谷氨酸的大量释放,导致运动网络阻滞。我们目前的目标是利用体内和体外模型评估 CREB 作为化学诱导脊髓损伤后损伤预测标志物的作用。因此,通过椎管内注射 KA 诱导 Balb/c 成年小鼠体内兴奋性中毒,而体外脊髓兴奋性中毒则是通过沐浴施加 KA 产生的。应用 KA 会诱发神经元大量缺失、后肢运动协调性恶化和热异感。此外,免疫组化分析表明,应用 KA 会导致腹侧角和背侧三至四层的 CREB 阳性核数目减少。我们的数据表明,兴奋毒性诱导的神经元损失可能是由 CREB 核转位的改变所预测的。
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引用次数: 0
Glucocorticoid alleviates hypothalamic nerve injury via remodeling HPA axis homeostasis in stressed rats 糖皮质激素通过重塑应激大鼠的 HPA 轴平衡缓解下丘脑神经损伤
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-28 DOI: 10.1016/j.bbr.2024.115223
Shanyong Yi , Bin Zhao , Lai Wei , Zhijun Yao , Bin Yang

Excessive stress can exceed the adjustment ability of body and cause injury and dysfunction, while elucidation of the mechanism and prevention measures of stress-related injury are still insufficient. The present study was to observe the effect of glucocorticoid (GC) on stress-induced hypothalamic nerve injury and elucidate the potential mechanism. The present study intended to establish a chronic restraint stress rat model for follow-up study. Open field test and elevated plus maze test were used to observe behavioral changes of stress rats; Enzyme-linked immunosorbent assay (ELISA) was used to detect changes in the levels of hypothalamus-pituitary-adrenal (HPA) axis-related hormones and inflammatory factors in hypothalamus; toluidine blue staining was used to observe pathological changes of hypothalamus. The results showed that stress rats showed obvious anxiety-like behaviors, the levels of HPA axis-related hormones and inflammatory factors showed abnormal fluctuations, and morphological results showed significant nerve injury in hypothalamus. Low-dose GC treatment significantly improved behavioral changes, alleviated hypothalamic nerve injury, and restored hypothalamic levels of inflammatory factors, serum levels of GC, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) and GC level in adrenal cortex of stressed rats, while GC receptor (GR) inhibitor, CRH receptor inhibitor, and adrenalectomy reversed the ameliorative effects of low-dose GC. Our study clarified that low-dose GC can restore stress coping ability by reshaping the homeostasis of the HPA axis, thus alleviating behavioral abnormalities and hypothalamic nerve injury in stressed rats.

过度应激会超出机体的调节能力,导致机体损伤和功能障碍,而应激相关损伤的机制和预防措施的阐明尚不充分。本研究旨在观察糖皮质激素(GC)对应激诱导的下丘脑神经损伤的影响,并阐明其潜在机制。本研究旨在建立一个慢性束缚应激大鼠模型进行后续研究。采用开阔地试验和高架迷宫试验观察应激大鼠的行为变化;采用酶联免疫吸附试验(ELISA)检测下丘脑-垂体-肾上腺(HPA)轴相关激素和下丘脑炎症因子水平的变化;采用甲苯胺蓝染色观察下丘脑的病理变化。结果显示,应激大鼠表现出明显的焦虑样行为,HPA轴相关激素和炎症因子水平出现异常波动,形态学结果显示下丘脑神经损伤明显。小剂量GC治疗可明显改善应激大鼠的行为变化,减轻下丘脑神经损伤,恢复下丘脑炎症因子水平、血清GC、促肾上腺皮质激素释放激素(CRH)和促肾上腺皮质激素(ACTH)水平以及肾上腺皮质GC水平,而GC受体(GR)抑制剂、CRH受体抑制剂和肾上腺切除术逆转了小剂量GC的改善作用。我们的研究明确了小剂量GC可以通过重塑HPA轴的平衡来恢复应激应对能力,从而缓解应激大鼠的行为异常和下丘脑神经损伤。
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引用次数: 0
AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice AQP4 在精神分裂症中上调,抑制 AQP4 可减轻 MK-801 诱导的小鼠精神分裂症样行为
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-28 DOI: 10.1016/j.bbr.2024.115220
Fa-yi Nie , Ru-yi Jin , Shan-shan Wu , Wei Yuan , Yu-wei Wu , Si-meng Xue , Xiao-hang Yang , Hai-fa Qiao

Background

The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms.

Methods

Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 μM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors.

Results

Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1β, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model.

Conclusions

AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.

背景精神分裂症(SCZ)的病理生理学和分子机制尚不清楚,有效的治疗资源仍然有限。方法在基因表达总库(Gene Expression Omnibus,GEO)数据库中检索PFC与健康对照组比较的微阵列数据集,用GEO2R在线工具分析差异表达基因(DEGs)。利用 Venny 在线工具和 metascape 在线软件识别常见的异常表达基因,并进行细胞类型特征富集分析。用NMDA受体拮抗剂MK-801诱导SCZ小鼠模型(腹腔注射,0.1 mg/kg/天,连续7天),用100 μM MK-801处理C6细胞模型。采用 RT-qPCR、Western 印迹法和免疫荧光法测定 AQP4、促炎细胞因子和 GFAP 的表达。结果生物信息学分析发现,与健康对照组相比,AQP4在SCZ患者的PFC中上调。细胞类型特征富集分析表明,所有三个DEGs列表都在FAN EMBRYONIC CTX ASTROCYTE 2类别中强富集。在MK-801处理的C6细胞和MK-801诱导的SCZ小鼠模型的PFC中也观察到了AQP4的上调。此外,用TGN-020(一种AQP4抑制剂)抑制AQP4可改善MK-801处理小鼠的焦虑样行为和社会新奇偏好缺陷。结论与健康对照组相比,AQP4在SCZ患者的PFC中上调。抑制AQP4可减轻MK-801处理的小鼠的焦虑样行为和社会新奇性缺陷,这可能是由于AQP4在调节促炎细胞因子表达中的作用。
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引用次数: 0
Frontal EEG alpha asymmetry predicts foreign language anxiety while speaking a foreign language 额叶脑电图阿尔法不对称预测说外语时的外语焦虑症
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-28 DOI: 10.1016/j.bbr.2024.115216
Brent Kelsen , Sophie Hsin-Yi Liang

Engaging in dialog requires interlocutors to coordinate sending and receiving linguistic signals to build a discourse based upon interpretations and perceptions interconnected with a range of emotions. Conversing in a foreign language may induce emotions such as anxiety which influence the quality communication. The neural processes underpinning these interactions are crucial to understanding foreign language anxiety (FLA). Electroencephalography (EEG) studies reveal that anxiety is often displayed via hemispheric frontal alpha asymmetry (FAA). To examine the neural mechanisms underlying FLA, we collected self-reported data on the listening and speaking sections of the Second language skill specific anxiety scale (L2AS) over behavioral, cognitive, and somatic domains and recorded EEG signals during participation in word chain turn-taking activities in first (L1, Chinese) and second (L2, English) languages. Regression analysis showed FAA for the L2 condition was a significant predictor primarily of the behavioral and somatic domains on the L2AS speaking section. The results are discussed along with implications for improving communication during L2 interactions.

参与对话需要对话者协调语言信号的发送和接收,以建立基于与一系列情感相互关联的解释和感知的话语。用外语对话可能会诱发焦虑等情绪,从而影响交流质量。这些相互作用的神经过程对于理解外语焦虑(FLA)至关重要。脑电图(EEG)研究显示,焦虑通常通过大脑半球额叶α不对称(FAA)表现出来。为了研究 FLA 的神经机制,我们收集了第二语言技能焦虑量表(L2AS)听力和口语部分的行为、认知和躯体领域的自我报告数据,并记录了第一语言(第一语言,中文)和第二语言(第二语言,英语)参与单词链轮流活动时的脑电信号。回归分析表明,第二语言条件下的 FAA 主要对第二语言口语部分的行为和躯体领域有显著的预测作用。本文讨论了这一结果以及对改善 L2 互动中的交流的影响。
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引用次数: 0
Enhancing spatial memory and pattern separation: Long-term effects of stimulant treatment in individuals with ADHD 增强空间记忆和模式分离:多动症患者接受兴奋剂治疗的长期效果。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-26 DOI: 10.1016/j.bbr.2024.115211
Francisco José Lobato-Camacho , Juan Carlos López , Juan Pedro Vargas

This study explores the under-researched domain of long-term stimulant treatment in children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The necessity for extended treatment duration, often accompanied by safety concerns and side effects leading to treatment discontinuation, underscores the significance of this investigation. Concurrently, comparative studies have revealed adverse impacts on vulnerable regions within the hippocampal formation, accompanied by behavioral perturbations. We employed computerized tests and virtual reality to assess spatial memory, pattern separation, and object recognition memory in a cohort of children diagnosed with ADHD receiving stimulant treatment. We compared their performance to a group of neurotypical peers. Our findings indicate that the ADHD group exhibited a lower performance in spatial memory, pattern separation, and object recognition memory than ND group. Intriguingly, a positive relationship emerged between the duration of stimulant treatment and performance in these variables. Notably, this improvement was not immediate to MPH treatment but becomes significant after 24 months of treatment. In contrast to previous comparative investigations, our study did not reveal a detrimental impact on spatial navigation, object recognition memory, or pattern separation, despite the known interplay of these cognitive processes with the hippocampal formation. These results shed new light on the nuanced effects of stimulant treatment in ADHD, underscoring the need for a more comprehensive understanding of long-term treatment outcomes.

本研究探讨了被诊断患有注意力缺陷多动障碍(ADHD)的儿童和青少年长期接受兴奋剂治疗这一研究不足的领域。由于必须延长治疗时间,而延长治疗时间往往伴随着安全问题和副作用,导致治疗中断,因此这项研究意义重大。与此同时,比较研究显示,药物对海马形成内的脆弱区域产生了不利影响,并伴有行为干扰。我们采用计算机化测试和虚拟现实技术,对一组接受兴奋剂治疗的多动症患儿的空间记忆、模式分离和物体识别记忆进行了评估。我们将他们的表现与一组神经正常的同龄人进行了比较。我们的研究结果表明,ADHD 组在空间记忆、模式分离和物体识别记忆方面的表现低于 ND 组。耐人寻味的是,兴奋剂治疗的持续时间与这些变量的表现之间出现了正相关。值得注意的是,这种改善并不是 MPH 治疗后立即出现的,而是在治疗 24 个月后变得显著。与以往的比较研究不同,我们的研究没有发现对空间导航、物体识别记忆或模式分离的不利影响,尽管这些认知过程与海马形成之间存在已知的相互作用。这些结果为了解兴奋剂治疗对多动症的细微影响提供了新的视角,强调了对长期治疗结果进行更全面了解的必要性。
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Behavioural Brain Research
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