Neuroscience最新文献_第4页

Chronic stress facilitates behavioral engagement and alters lateral habenula activity during flexible decision making in a sex-dependent manner 慢性压力促进行为参与和改变侧缰活动在灵活的决策在性别依赖的方式。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.031

Hayden R. Wright , Zachary D.G. Fisher , Ryan M. Schmid , Sara R. Westbrook , Riana A. Abeshima , Giuseppe Giannotti , Ryan J. McLaughlin

The ability to integrate feedback and flexibly adjust behavior under shifting environmental demands is required to optimize decision-making strategies. Clinical and preclinical data indicate that individuals with stress-related disorders and rodents exposed to chronic stress exhibit impaired behavioral flexibility. The lateral habenula (LHb) has emerged as a key brain region contributing to the effects of stress on cognitive performance. However, the extent to which the LHb is recruited to fine-tune decision-making strategies, as well as the impacts of chronic stress on LHb recruitment during task performance, remain largely unknown. To this end, we used a three-week model of chronic unpredictable stress (CUS) and performed in vivo fiber photometry to investigate Ca²⁺ transients in LHb neurons during an attentional set-shifting task in adult male and female Sprague Dawley rats (n = 7–12/sex/group). We found that CUS exposure did not significantly impair behavioral flexibility. Rather, CUS-exposed rats made fewer omissions and exhibited shorter response latencies compared to controls, suggesting enhanced task engagement. We also observed sex differences in LHb Ca²⁺ activity. In control animals, we found that male rats showed greater inhibition of LHb signal prior to decision making, and greater activation following trial outcome than females. These differences were normalized by CUS, resulting in similar signaling patterns across sexes. Altogether, these findings reveal that chronic stress alters LHb activity in a sex-dependent manner without overtly impairing behavioral flexibility.

在不断变化的环境需求下，需要整合反馈和灵活调整行为的能力来优化决策策略。临床和临床前数据表明，患有压力相关疾病的个体和暴露于慢性压力下的啮齿动物表现出行为灵活性受损。侧缰（LHb）已经成为一个关键的大脑区域，有助于影响压力对认知能力的影响。然而，LHb在多大程度上被招募来微调决策策略，以及在任务执行过程中慢性压力对LHb招募的影响，在很大程度上仍然未知。为此，我们使用了一个为期三周的慢性不可预测应激（CUS）模型，并进行了体内纤维光度法研究成年雄性和雌性Sprague Dawley大鼠（n = 7-12/性别/组）在注意力转移任务期间LHb神经元中的Ca2+瞬态。我们发现，接触CUS并没有显著损害行为灵活性。相反，与对照组相比，暴露于cu的大鼠出现更少的遗漏，表现出更短的反应延迟，表明增强了任务参与。我们还观察到LHb Ca2+活性的性别差异。在对照动物中，我们发现雄性大鼠在决策前表现出更大的LHb信号抑制，在试验结果后表现出更大的激活。这些差异被CUS归一化，导致两性之间的信号模式相似。总之，这些发现揭示了慢性应激以性别依赖的方式改变LHb活性，而不会明显损害行为灵活性。

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引用次数: 0

METTL14 promotes ischemic stroke pathogenesis by mediating m6A methylation modification of BACH1 to enhance OGD/R-induced neuronal damage and facilitate ferroptosis in SK-N-SH cells. METTL14通过介导BACH1的m6A甲基化修饰，增强OGD/ r诱导的神经元损伤，促进SK-N-SH细胞铁凋亡，从而促进缺血性卒中的发病机制。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.037

Chuang Cui, Lei Feng, Long Su, Li Wang, Liping Xie

Background: Ischemic stroke (IS) is an acute cerebrovascular condition marked by high prevalence, high disability and high mortality rates. Previous studies have indicated that BTB and CNC homology 1 (BACH1) promotes ferroptosis in IS. However, the research on its specific molecular mechanism remains at an early stage.

Methods: To mimic the cell models of IS, SK-N-SH cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Protein levels were tested by Western blot. CCK-8, TUNEL, flow cytometry, and Enzyme-linked Immunosorbent assay were employed to monitor viability, apoptosis, and inflammatory response. Additionally, Fe²⁺, malondialdehyde (MDA), glutathione (GSH) and reactive oxygen species (ROS) levels were detected using relevant kits. Methylated RNA immunoprecipitation (MeRIP) and RIP assays were used to analyze the methylation modification and the binding interactions between molecules. BACH1 mRNA level was examined by qRT-PCR. Finally, an animal model of IS was established using middle cerebral artery occlusion (MCAO) to further validate the in-vitro findings.

Results: Silencing BACH1 alleviated injury in OGD/R-induced SK-N-SH cells. METTL14 and IGF2BP1 cooperatively enhanced BACH1 expression via an m6A-dependent mechanism. Overexpression of BACH1 reversed the protective effects of METTL14 silencing. Moreover, METTL14 inhibited the Nrf2/SLC7A11/GPX4 pathway by stabilizing BACH1. BACH1 downregulation attenuated IS progression in vivo.

Conclusion: The METTL14/IGF2BP1 complex stabilizes BACH1 mRNA through m6A modification. This leads to suppression of the Nrf2/SLC7A11/GPX4 pathway, promotion of ferroptosis, and ultimately exacerbation of IS.

背景：缺血性脑卒中是一种发病率高、致残率高、死亡率高的急性脑血管疾病。先前的研究表明BTB和CNC同源1 （BACH1）促进IS的铁下垂。然而，对其具体分子机制的研究尚处于早期阶段。方法：采用氧-葡萄糖剥夺/再氧化（OGD/R）诱导SK-N-SH细胞，模拟IS细胞模型。Western blot检测蛋白水平。采用CCK-8、TUNEL、流式细胞术和酶联免疫吸附法监测细胞活力、细胞凋亡和炎症反应。采用相关试剂盒检测Fe2+、丙二醛（MDA）、谷胱甘肽（GSH）和活性氧（ROS）水平。甲基化RNA免疫沉淀（MeRIP）和RIP检测分析了甲基化修饰和分子间的结合相互作用。采用qRT-PCR检测BACH1 mRNA水平。最后，采用大脑中动脉闭塞法（MCAO）建立IS动物模型，进一步验证体外实验结果。结果：沉默BACH1可减轻OGD/ r诱导的SK-N-SH细胞损伤。METTL14和IGF2BP1通过m6a依赖机制共同增强BACH1的表达。BACH1的过表达逆转了METTL14沉默的保护作用。此外，METTL14通过稳定BACH1抑制Nrf2/SLC7A11/GPX4通路。BACH1下调可减弱IS在体内的进展。结论：METTL14/IGF2BP1复合物通过m6A修饰稳定BACH1 mRNA。这导致Nrf2/SLC7A11/GPX4通路的抑制，促进铁下垂，最终加重IS。

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引用次数: 0

Short-term high-fat diet impairs anterograde and retrograde memory consolidation, but not retrieval in aged rats 短期高脂肪饮食损害老年大鼠的顺行和逆行记忆巩固，但不影响检索。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.028

Bryan D. Alvarez , Jayden D. Milligan , Zoha H. Khan , Ruth M. Barrientos

Background

Aging increases vulnerability to cognitive decline, and ultraprocessed diets high in saturated fat may accelerate this trajectory. Although short-term high-fat diet (HFD) exposure is known to impair memory in aged animals, the specific stages of memory most susceptible to short-term HFD remain unclear.

Methods

This study examined how short-term HFD influences anterograde consolidation, retrograde consolidation, and retrieval of long-term fear memory in aged rats. Male F344 × BN F1 rats (22–24 months) consumed chow or three days of HFD provided at distinct times relative to contextual and cued fear conditioning to isolate each memory phase. Importantly, this brief HFD protocol minimizes metabolic disturbances typically produced by longer-term diet manipulation, allowing us to isolate the effects of macronutrient composition on memory processes.

Results

Three days of HFD before or immediately after conditioning significantly impaired contextual and cued fear memory, reflecting disrupted anterograde and retrograde consolidation. In contrast, three days of HFD before retrieval had no effect on memory performance.

Conclusion

These findings demonstrate that short-term consumption of ultraprocessed HFD selectively impairs consolidation while sparing retrieval of hippocampal- and amygdala-dependent memory in aging. These findings are important because identifying the specific memory processes that are disrupted, rather than global memory dysfunction, helps narrow mechanistic targets and informs the development of more precise interventions to mitigate diet-related cognitive decline in aging.

背景：衰老增加认知能力下降的脆弱性，高饱和脂肪的超加工饮食可能加速这一轨迹。虽然已知短期高脂肪饮食（HFD）暴露会损害老年动物的记忆，但最容易受到短期高脂肪饮食影响的记忆的具体阶段仍不清楚。方法：研究短期HFD对老年大鼠长期恐惧记忆的顺行巩固、逆行巩固和恢复的影响。雄性F344 × BN F1大鼠（22-24 个月）在不同的时间消耗相对于情境和暗示恐惧条件反射提供的食物或三天的HFD来隔离每个记忆阶段。重要的是，这个简短的HFD方案最大限度地减少了通常由长期饮食控制产生的代谢紊乱，使我们能够分离出宏量营养素组成对记忆过程的影响。结果：在条件反射之前或之后的三天，HFD显著损害了情境和线索恐惧记忆，反映了逆行和逆行巩固的中断。相比之下，检索前三天的HFD对记忆性能没有影响。结论：这些研究结果表明，短期食用超加工的HFD选择性地损害了衰老过程中海马和杏仁核依赖性记忆的巩固，同时保留了记忆的恢复。这些发现很重要，因为确定被破坏的特定记忆过程，而不是全局记忆功能障碍，有助于缩小机制目标，并为开发更精确的干预措施提供信息，以减轻与饮食有关的认知衰退。

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引用次数: 0

Therapeutic efficacy of synthetic analogues of gut hormones in a mouse model of Alzheimer's disease. 肠道激素合成类似物对阿尔茨海默病小鼠模型的治疗效果

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.038

Paul Denver, Aisling Duffy, Rebecca T Kennedy, Victor A Gault, Paula L McClean

Alzheimer's disease (AD) is a neurodegenerative condition characterised by amyloid-β pathology, neuroinflammation, synaptic dysfunction and cognitive decline. Few pharmacological interventions are available, offering only symptomatic relief, and approval for a number of anti-amyloid biologics is limited, with concerns about safety, cost and efficacy. Here we investigated the effects of 8-10 weeks treatment with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], long-lasting analogues of gut hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and xenin-25, respectively, in the APP/PS1 mouse model of AD. Cognitive function was measured in novel object recognition (NOR) and Morris water maze (MWM) tasks and amyloid burden, gliosis, synapse density and neurogenesis were assessed in brains of APP/PS1 and wild-type mice. AD-associated gene expression analysis was performed to identify potential pathways targeted by treatment. Liraglutide and NAcGIP[Lys(37)PAL] improved cognitive performance in APP/PS1 mice and, along with Xenin-25[Lys(13)PAL], reduced amyloid-β burden in the brain. Liraglutide ameliorated gliosis and all three treatments restored synaptophysin levels. Additionally, Xenin-25[Lys(13)PAL] increased neurogenesis in the dentate gyrus. Numerous AD-associated genes were altered in the brain following treatments. Notably, Serpina3c was upregulated in brains of APP/PS1 mice treated with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], while Map2, Adam9, Lrp8, Casp3, Abca1 and App were downregulated. These results underscore the neuroprotective effects of liraglutide and suggest that NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL] possess neuroprotective properties. Further investigation of the precise nature of these effects may support development of multi-target therapeutics based on combinations of gut hormone analogues.

阿尔茨海默病（AD）是一种以淀粉样蛋白-β病理、神经炎症、突触功能障碍和认知能力下降为特征的神经退行性疾病。很少有药物干预可用，仅提供症状缓解，并且由于对安全性，成本和有效性的担忧，许多抗淀粉样蛋白生物制剂的批准有限。本研究研究了利拉鲁肽、NAcGIP[Lys(37)PAL]和Xenin-25[Lys(13)PAL]（肠道激素胰高血糖素样肽-1 （GLP-1）、葡萄糖依赖性胰岛素肽（GIP）和Xenin-25的长效类似物）治疗8-10 周对APP/PS1 AD小鼠模型的影响。在新目标识别（NOR）和Morris水迷宫（MWM）任务中测量认知功能，并评估APP/PS1和野生型小鼠大脑的淀粉样蛋白负担、胶质细胞增生、突触密度和神经发生。进行ad相关基因表达分析，以确定治疗靶向的潜在途径。利拉鲁肽和NAcGIP[Lys(37)PAL]改善了APP/PS1小鼠的认知能力，并与Xenin-25[Lys(13)PAL]一起减少了大脑中的淀粉样蛋白-β负担。利拉鲁肽改善胶质瘤，所有三种治疗均恢复突触素水平。此外，Xenin-25[Lys(13)PAL]增加齿状回的神经发生。治疗后，大脑中许多ad相关基因发生了改变。值得注意的是，利拉鲁肽、NAcGIP[Lys(37)PAL]和Xenin-25[Lys(13)PAL]处理的APP/PS1小鼠脑内Serpina3c上调，Map2、Adam9、Lrp8、Casp3、Abca1和APP下调。这些结果强调了利拉鲁肽的神经保护作用，并表明NAcGIP[Lys(37)PAL]和Xenin-25[Lys(13)PAL]具有神经保护作用。对这些效应的确切性质的进一步研究可能支持基于肠道激素类似物组合的多靶点治疗的发展。

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引用次数: 0

High-frequency rTMS over the left ventrolateral prefrontal cortex ameliorates gastrointestinal injury in patients with stroke: an fNIRS-HRV study 高频rTMS在左腹外侧前额叶皮层改善脑卒中患者胃肠道损伤：一项fNIRS-HRV研究。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.029

Lin Lv , Zhenyan Zhang , Jun Zhang , Fengli Bi , Xueqin Liang , Xinyi Li , Chunxiao Wan

Autonomic dysfunction resulting from damage to the central autonomic network is a common complication of acquired brain injury (ABI). The prefrontal and insular cortices regulate visceromotor autonomic functions, and gastrointestinal dysfunction following ABI may involve impaired autonomic innervation. While repetitive transcranial magnetic stimulation (rTMS) shows potential for studying the top-down control of visceral processes, the mechanisms linking disrupted functional connectivity to autonomic dysfunction and the restorative effects of neuromodulation remain unclear.

Sixty-four ABI patients with acute gastrointestinal injury (AGI) were randomized into a control group (CG, n = 32) and an rTMS group (TG, n = 32). Both groups received standard rehabilitation, while the TG additionally underwent 10 Hz rTMS over the left ventrolateral prefrontal cortex (VLPFC-L) (five sessions per week for two weeks). Autonomic function was assessed via heart rate variability (HRV), and whole-brain functional connectivity was measured using 106-channel functional near-infrared spectroscopy (fNIRS). Graph-theoretical network metrics were analyzed.

Compared to the CG, the TG showed reduced acute gastrointestinal injury scores, decreased low-frequency (LF) power, a lower low-frequency to high-frequency (LF/HF) ratio, and increased high-frequency (HF) power. Functional connectivity increased in the left ventrolateral prefrontal cortex (VLPFC-L), particularly with the right frontal pole, bilateral premotor cortices, and the left pre-motor/supplementary motor cortex. Global and local network efficiency also improved.

These findings indicate that VLPFC-L-targeted rTMS can restore neuroautonomic integration and gastrointestinal function in ABI patients. This study demonstrates the potential of fNIRS and HRV as complementary tools for assessing the effects of neuromodulation on autonomic circuits.

由中枢自主神经网络损伤引起的自主神经功能障碍是后天性脑损伤（ABI）的常见并发症。前额叶和岛叶皮质调节内脏运动自主神经功能，ABI后的胃肠道功能障碍可能涉及自主神经支配受损。虽然重复经颅磁刺激（rTMS）显示出研究内脏过程自上而下控制的潜力，但将功能连接中断与自主神经功能障碍和神经调节的恢复作用联系起来的机制仍不清楚。将64例ABI合并急性胃肠道损伤（AGI）患者随机分为对照组（CG, n = 32）和rTMS组（TG, n = 32）。两组均接受标准康复治疗，而TG在左侧腹外侧前额叶皮层（VLPFC-L）上额外接受10 Hz rTMS（每周5次，持续两周）。自主神经功能通过心率变异性（HRV）评估，全脑功能连接使用106通道功能近红外光谱（fNIRS）测量。分析了图论网络指标。与CG相比，TG表现出急性胃肠道损伤评分降低，低频（LF）功率降低，低频与高频（LF/HF）之比降低，高频（HF）功率增加。左腹外侧前额叶皮层（VLPFC-L）的功能连通性增加，特别是与右额极，双侧运动前皮层和左运动前/辅助运动皮层。全球和本地网络效率也有所提高。这些结果表明，以vlpfc - l为靶点的rTMS可以恢复ABI患者的神经自主整合和胃肠道功能。这项研究证明了fNIRS和HRV作为评估神经调节对自主神经回路影响的补充工具的潜力。

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引用次数: 0

Effects of different noisy galvanic vestibular stimulation frequencies on postural control responses 不同噪声前庭电刺激频率对体位控制反应的影响。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.032

Tsubasa Mitsutake , Motomichi Sonobe

Noisy galvanic vestibular stimulation (nGVS) can improve postural stability by delivering subthreshold electrical noise to the vestibular system. However, the frequency-specific effects of nGVS on postural control responses—particularly those involving the center of mass (COM) recovery force and movement strategies—remain unclear. We investigated how different nGVS frequencies affect postural control, estimating COM fluctuations using a rigid pendulum model. Thirty-two healthy adults (mean age, 20.3 ± 1.2 years; 19 females) underwent three interventions: sham nGVS, low-frequency nGVS (LF-nGVS, 0–100 Hz), or high-frequency nGVS (HF-nGVS, 100–640 Hz), each with a 200 µA current (0 µA for the sham). During each 40-s trial, participants stood on a platform with eyes closed and the middle 30 s were analyzed. Inertial measurement units were affixed to the occipital protuberance to capture head kinematics. Postural control was assessed using conventional metrics (e.g., center of foot pressure [COP], COM sway, and head acceleration) and novel indicators of COM recovery force and head acceleration control based on motor strategies. Both LF-nGVS and HF-nGVS significantly reduced several indices, including COP velocity and head angular velocity, compared with sham stimulation. No significant differences were observed between LF-nGVS and HF-nGVS. Head acceleration was significantly correlated with COM recovery force and joint movement strategies in both stimulation conditions. Although the mechanism of neural network activity at different stimulation frequencies requires careful interpretation, these findings suggest that COM recovery and associated motor strategies contribute to nGVS-induced postural improvements, providing insights into its neuromechanistic effects.

噪声前庭电刺激（nGVS）可以通过向前庭系统传递阈下电噪声来改善姿势稳定性。然而，nGVS对姿势控制反应的频率特异性影响，特别是涉及质心恢复力和运动策略的影响，仍不清楚。我们研究了不同的nGVS频率如何影响姿势控制，使用刚性摆模型估计COM波动。32名健康成年人（平均年龄20.3 ± 1.2 岁；19名女性）接受了三种干预：假性nGVS、低频nGVS（低频-nGVS， 0-100 Hz）或高频nGVS（低频-nGVS， 100-640 Hz），每种干预的电流为200µa（假性为0µa）。在每一次40秒的试验中，参与者闭着眼睛站在一个平台上，然后分析中间的30秒 。惯性测量单元被贴在枕骨突起以捕捉头部运动学。姿势控制采用常规指标（如足压力中心[COP]、头部摆动和头部加速度）和基于运动策略的头部恢复力和头部加速度控制的新指标进行评估。与假刺激相比，LF-nGVS和HF-nGVS均显著降低了COP速度和头部角速度等多项指标。LF-nGVS与HF-nGVS之间无显著差异。在两种刺激条件下，头部加速度与COM恢复力和关节运动策略显著相关。尽管不同刺激频率下神经网络活动的机制需要仔细解释，但这些发现表明，COM恢复和相关的运动策略有助于ngvs诱导的姿势改善，为其神经机制效应提供了见解。

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引用次数: 0

Experimentally induced fatigue and motor learning: A scoping review 实验诱导疲劳和运动学习：范围综述。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.030

Bahram Ghafari Goushe , Layale Youssef , Thomas Mangin , Denis Arvisais , Jason L. Neva , Benjamin Pageaux

The literature on the effect of fatigue on motor learning is limited and marked by inconsistent findings. This scoping review aimed to explore the available knowledge on the effects of fatigue induced by physical and cognitive exertion on motor learning, and to compile and understand how it is studied. A comprehensive search strategy using relevant index terms and keywords was conducted across MEDLINE, EMBASE, SPORTDiscus, Web of Science, PsycINFO, CINAHL, ERIC, and Dissertations & Theses Global. Twenty-five studies met the inclusion criteria. The findings revealed considerable inconsistencies in how fatigue and motor learning were defined and measured. None of the studies examined the effect of fatigue induced by combined physical and cognitive exertion, and only 7 studies investigated fatigue induced by cognitive exertion. Acuity tasks were the most frequently used to assess motor learning, employed in 14 studies. Notably, all participants were between 16.5 and 31 years of age, and reporting of key demographic and physiological characteristics such as sex, gender, physical activity level, and body mass index was inconsistent or absent. This review highlights the need for comprehensive definitions of both fatigue and motor learning to improve consistency and reproducibility across studies. Given the limited research on the effects of fatigue induced by cognitive and combined physical and cognitive exertion, future studies should prioritize using these experimental manipulations. Also, future studies should diversify the motor learning tasks used in research to allow both direct and conceptual replication. Additionally, broader age ranges and comprehensive participant profiling should be prioritized.

关于疲劳对运动学习的影响的文献是有限的，并且以不一致的发现为标志。本综述旨在探讨体力和认知消耗引起的疲劳对运动学习影响的现有知识，并汇编和了解其研究方式。在MEDLINE、EMBASE、SPORTDiscus、Web of Science、PsycINFO、CINAHL、ERIC和disserts&theses Global等平台上使用相关索引词和关键词进行了全面的搜索策略。25项研究符合纳入标准。研究结果显示，疲劳和运动学习的定义和测量存在相当大的不一致性。没有一项研究调查了体力和认知联合消耗引起的疲劳的影响，只有7项研究调查了认知消耗引起的疲劳。在14项研究中，敏锐度任务是评估运动学习最常用的方法。值得注意的是，所有参与者的年龄都在16.5到31 岁之间，关键的人口统计学和生理特征（如性别、性别、身体活动水平和体重指数）的报告不一致或缺失。这篇综述强调需要对疲劳和运动学习进行全面的定义，以提高研究的一致性和可重复性。鉴于目前对认知及体能与认知联合运动引起的疲劳影响的研究有限，未来的研究应优先使用这些实验操作。此外，未来的研究应该使研究中使用的运动学习任务多样化，以允许直接和概念复制。此外，应优先考虑更广泛的年龄范围和全面的参与者分析。

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引用次数: 0

Unravelling the impact on attention and emotions on neurophysiological responses to a multisensory experience of nature 揭示对自然的多感官体验对注意力和情绪的神经生理反应的影响

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-26 DOI: 10.1016/j.neuroscience.2026.01.034

Damien Gabriel , Pierre-Edouard Billot , Sylvie Tufeu , Eric Fernandez , Stéphanie Brédif , Florine Maylié , Karena Moretto , Virginie Fera , Julie Giustiniani

Exposure to natural environments has been linked to improved well-being, reduced stress, and enhanced attention. This study examined neurophysiological and behavioral effects of multisensory nature exposure (visual, auditory, and olfactory) compared to urban environments. Thirty-two right-handed women (25–49 years) performed a Go/No-Go task while EEG, electrodermal activity (EDA), and heart rate (HR) were recorded. Participants experienced images alone, images with sounds, images with odors, and images with both sounds and odors. Behavioral results showed improved task performance in natural environments, with more correct responses. However, odor-enriched conditions increased errors, suggesting that olfactory inputs may interfere with attention. Psychophysiological measures indicated lower skin conductance response (SCR) frequency in natural environments, especially under multisensory stimulation, consistent with reduced sympathetic arousal. EEG data revealed clear neural differences: the P1-N1 complex, linked to attentional effort, had greater amplitude in urban contexts, while the early posterior negativity (EPN), related to emotional processing, was stronger in natural conditions. Source localization associated EPN effects with the right occipital and inferior frontal gyrus. These findings support Attention Restoration Theory (ART) and Stress Reduction Theory (SRT), highlighting nature’s restorative potential. Sensory enrichment appeared to strengthen emotional engagement while modulating attentional performance. Results emphasize the value of multisensory perspectives in environmental neuroscience and point to EEG biomarkers as sensitive indicators of cognitive and affective processes. Future work should extend these insights to real-world settings using mobile neurophysiological methods.

暴露在自然环境中可以改善幸福感，减少压力，提高注意力。本研究考察了与城市环境相比，多感官自然暴露（视觉、听觉和嗅觉）对神经生理和行为的影响。32名右撇子女性（25-49岁）在执行Go/No-Go任务的同时记录脑电图、皮肤电活动（EDA）和心率（HR）。参与者分别体验了单独的图像、有声音的图像、有气味的图像以及既有声音又有气味的图像。行为结果显示，在自然环境中，任务表现得到改善，反应更正确。然而，气味丰富的环境会增加错误，这表明嗅觉输入可能会干扰注意力。心理生理学测量表明，在自然环境中，特别是在多感觉刺激下，皮肤电导反应（SCR）频率较低，与交感神经觉醒降低一致。脑电图数据显示了明显的神经差异：与注意力努力相关的P1-N1复合物在城市环境中振幅更大，而与情绪处理相关的早期后验负性（EPN）在自然环境中更强。源定位与EPN对右侧枕回和额下回的影响相关。这些发现支持了注意力恢复理论（ART）和压力减轻理论（SRT），强调了自然的恢复潜力。感觉丰富似乎在调节注意力表现的同时加强了情感投入。结果强调了多感官视角在环境神经科学中的价值，并指出脑电图生物标志物是认知和情感过程的敏感指标。未来的工作应该使用移动神经生理学方法将这些见解扩展到现实世界。

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引用次数: 0

Epigenetic regulation of aggression-linked genes following prenatal stress enhances risk for sexual aggression in male rat offspring 产前应激后攻击相关基因的表观遗传调控增加了雄性大鼠后代性攻击的风险。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-25 DOI: 10.1016/j.neuroscience.2026.01.033

Elvis Mbiydzenyuy Ngala , Sian Megan Joanna Hemmings , Jacqueline Samantha Womersley , Tarryn Willmer , Thando W. Shabangu , Lihle Qulu-Appiah

Early-life psychosocial adversity can shape adult behaviour through enduring epigenetic mechanisms, yet the neurobiological pathways linking parental stress to offspring socio-affective behaviour remain incompletely understood. Here, we investigated whether paternal social isolation and maternal prenatal stress are associated with persistent DNA methylation differences in aggression- and stress-related neurochemical receptor genes in male rat offspring, and whether these molecular alterations co-occur with changes in aggression-like and maladaptive mating behaviour. Male Wistar rats were generated from F0 males housed either in groups or in social isolation and from dams exposed to prenatal restraint stress or control conditions. In adulthood, male offspring were assessed for aggression-like behaviour using the resident–intruder test and for maladaptive mating attempts toward non-receptive females using the Sexual Aggression Test, a rodent paradigm capturing forced or inappropriate mating behaviour. Targeted DNA methylation profiling of the androgen receptor, corticotropin-releasing hormone receptor 1, oxytocin receptor, and serotonin receptor 1A genes was performed using pyrosequencing in the amygdala, hippocampus, hypothalamus, and prefrontal cortex. Paternal social isolation was associated with increased methylation of stress- and androgen-related genes in limbic and prefrontal regions, whereas prenatal stress was linked to region-specific alterations in oxytocinergic and serotonergic gene methylation. These epigenetic patterns co-occurred with heightened aggression-like behaviour and increased maladaptive mating attempts in offspring from stress-exposed lineages. Despite modest methylation effects and model limitations, the findings suggest paternal and prenatal stress jointly shape offspring socio-affective behaviour through region-specific epigenetic variation.

早期生活中的社会心理逆境可以通过持久的表观遗传机制塑造成年后的行为，然而，将父母压力与后代社会情感行为联系起来的神经生物学途径仍然不完全清楚。在这里，我们研究了父亲的社会隔离和母亲的产前压力是否与雄性大鼠后代中攻击和压力相关的神经化学受体基因的持续DNA甲基化差异有关，以及这些分子改变是否与攻击样和适应不良的交配行为的变化共同发生。雄性Wistar大鼠是由群体饲养或社会隔离的母鼠和暴露于产前约束压力或控制条件下的母鼠产生的。成年后，研究人员使用“常驻入侵者”测试评估雄性后代的攻击性行为，并使用“性侵犯测试”评估雄性后代对不接受交配的雌性的不适应交配尝试。利用焦磷酸测序技术对杏仁核、海马、下丘脑和前额皮质的雄激素受体、促肾上腺皮质激素释放激素受体1、催产素受体和血清素受体1A基因进行靶向DNA甲基化分析。父亲的社会隔离与边缘和前额叶区域压力和雄激素相关基因甲基化增加有关，而产前压力与催产素和血清素能基因甲基化的区域特异性改变有关。这些表观遗传模式与来自压力暴露谱系的后代的攻击性行为增强和适应不良的交配尝试增加共同发生。尽管有适度的甲基化效应和模型局限性，研究结果表明，父亲和产前压力通过区域特异性表观遗传变异共同塑造了后代的社会情感行为。

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引用次数: 0

TLR2 regulation of NF-κB and NLRP3-driven pyroptosis in Alzheimer’s disease TLR2调节NF-κB和nlrp3驱动的阿尔茨海默病焦亡。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2026-01-23 DOI: 10.1016/j.neuroscience.2026.01.026

Lijun Zhang , Shuo Wang , Yongkun Gui , Dongli Li , Kunyan Li , Yayu Wang , Yuming Xu

Although upregulation of toll-like receptor 2 (TLR2) excessively activates pro-inflammatory microglia through Aβ peptides, it remains unclear whether TLR2 regulates neuronal pyroptosis via the NF-κB/NLRP3 pathway in Alzheimer’s disease (AD). We assessed TLR2 expression in peripheral blood from clinical samples and employed SH-SY5Y cells for initial screening. AD pathology was simulated by Aβ_1-42 stimulation, and pathway regulatory relationships were dissected through TLR2 knockdown, NF-κB overexpression, and NLRP3 activation experiments. APP/PS1 mice were treated with sh-TLR2. Results demonstrated that high TLR2 expression activated the NF-κB/NLRP3 pathway and promoted pyroptosis, while TLR2 silencing suppressed Aβ_1-42-driven pyroptosis in SH-SY5Y cells by inhibiting this pathway. NF-κB overexpression or NLRP3 activation partially reversed the protective effect of TLR2 silencing. In vivo experiments confirmed the role of TLR2 knockdown in AD mice. Thus, this study revealed that TLR2 drives neuronal pyroptosis via the NF-κB/NLRP3 pathway, providing a novel therapeutic target for AD. These findings complement existing microglia-centered TLR2 research and broadens the understanding of neuroinflammatory regulation. However, SH-SY5Y cells differ from primary neurons in maturity, which may limit mechanistic extrapolation. Further validation in induced pluripotent stem cells-derived primary neurons or humanized mouse models will enhance the clinical translational potential of these findings.

虽然toll样受体2 （TLR2）的上调通过Aβ肽过度激活促炎小胶质细胞，但TLR2是否通过NF-κB/NLRP3通路调节阿尔茨海默病（AD）的神经元焦亡尚不清楚。我们评估了临床样本外周血中TLR2的表达，并使用SH-SY5Y细胞进行初步筛选。通过a - β1-42刺激模拟AD病理，通过TLR2敲低、NF-κB过表达、NLRP3激活实验解剖通路调控关系。应用sh-TLR2处理APP/PS1小鼠。结果表明，TLR2的高表达激活了NF-κB/NLRP3通路，促进了SH-SY5Y细胞的焦亡，而TLR2的沉默通过抑制该通路抑制了a β1-42驱动的SH-SY5Y细胞的焦亡。NF-κB过表达或NLRP3激活部分逆转了TLR2沉默的保护作用。体内实验证实了TLR2敲低在AD小鼠中的作用。因此，本研究揭示了TLR2通过NF-κB/NLRP3通路驱动神经元焦亡，为AD的治疗提供了新的靶点。这些发现补充了现有的以小胶质细胞为中心的TLR2研究，拓宽了对神经炎症调节的理解。然而，SH-SY5Y细胞在成熟时与原代神经元不同，这可能限制了机制外推。在诱导多能干细胞衍生的原代神经元或人源化小鼠模型中进一步验证将增强这些发现的临床转化潜力。

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引用次数: 0