Neuroscience最新文献_第9页

S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress 在压力动物模型中，S-(+)-麦角胺能提高血清素神经元的发射率，减少类似抑郁的行为。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-24 DOI: 10.1016/j.neuroscience.2024.10.043

A. Mondragón-García , E. Ramírez-Sánchez , D. Francia-Ramírez , O. Hernández-González , Y. Rojano-Posada , S. Ortega-Tinoco , J. Garduño , L. Verdugo-Díaz , S. Hernández-López

Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(−)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.

美卡拉明是烟碱乙酰胆碱受体（nAChRs）的非竞争性阻断剂，是两种立体异构体的外消旋混合物：S-(+)-mecamylamine (S-mec) 和 R-(-)-mecamylamine (R-mec)，与 α4β2 nAChRs 的相互作用截然不同。研究表明，麦角胺能增加谷氨酸的释放并兴奋背侧剑突核（DRN）中的5-羟色胺能（5-HT）神经元。在本研究中，我们分别评估了 S-mec 和 R-mec 对 5-HT 神经元兴奋性的影响。S-mec（3 μM）能使发射频率增加 40%，而 R-mec（3 μM）只能使发射频率增加 22%。S-mec 对谷氨酸末端的高灵敏度（HS）α4β2 nAChRs 起着正异位调节作用，可增强 5-HT 神经元的自发兴奋性突触后电流（sEPSCs）。相反，R-mec 通过阻断 HS α4β2 nAChRs 减少了 sEPSCs，并通过阻断 GABA 能终端的 α7 nAChRs 减少了 GABA 介导的抑制电流（sIPSCs）。这些机制使 S-mec 在增强 5-HT 神经元发射方面比 R-mec 更有效。此外，将 S-mec 与 HS α4β2 nAChRs 的选择性激动剂 TC-2559 结合使用，可使发射频率增加 65%，超过了 S-mec 单独使用的效果。为了验证这些发现，我们评估了S-mec（1 mg/kg）与另一种α4β2 nAChR激动剂TC-2559或RJR-2403联合使用的抗抑郁效果。这种组合成功地减少了类似抑郁症的行为，为对传统抗抑郁药产生抗药性的患者提供了一种潜在的治疗策略。

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引用次数: 0

Nitric oxide synthase system in the brain development of neonatal hypothyroid rats. 新生甲状腺功能减退大鼠大脑发育过程中的一氧化氮合酶系统

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-24 DOI: 10.1016/j.neuroscience.2024.10.040

Juan Carlos López-Ramos, Esther Martínez-Lara, Julia Serrano, Patricia Fernández, Gloria G Parras, Antonio Ruiz-Marcos, José Rodrigo

Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal development and plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals.

甲状腺激素在胎儿期和新生儿期发挥着重要的形态发生作用，并调节着许多新陈代谢过程。在中枢神经系统中，它们控制着髓鞘化和大脑的整体发育、区域基因表达以及耗氧量的调节。在胎儿期和新生儿期，由于缺乏甲状腺功能或碘缺乏，它们的缺乏会导致严重的智力迟钝。同时，一氧化氮是一种非典型神经递质，在神经元的发育和可塑性方面也有特殊意义，并具有血管扩张剂的功能，可调节脑血流量。虽然在生理条件下，它具有保护神经的功能，但过量时也会对神经产生毒性。我们通过免疫细胞化学和 Western 印迹技术，研究了一氧化氮合酶的神经元和诱导型同工酶，以及一氧化氮存在时蛋白质硝化的标志物硝基酪氨酸在出生后大脑发育早期阶段的表达变化。我们从妊娠第七天开始给孕妇注射巯甲基咪唑，诱发甲状腺功能减退症，直至后代被处死。结果显示，在甲状腺功能减退的动物体内，一氧化氮合酶的两种同工酶的表达延迟演变，随后在后期出现异常过度表达。最后，硝基酪氨酸的表达与对照组和甲状腺机能减退动物体内两种同工酶的表达同步进行。

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引用次数: 0

Modulation of tenofovir by probenecid: Impact on drug, interleukin-1β, and dopamine concentration in the prefrontal cortex and cerebellum 丙磺舒对替诺福韦的调节作用：对药物、白细胞介素-1β以及前额叶皮层和小脑中多巴胺浓度的影响

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-24 DOI: 10.1016/j.neuroscience.2024.10.031

Simangele NE Shabalala, M. Luvuno, M.V. Mabandla

The blood–brain barrier’s limited permeability to tenofovir restricts its ability to clear HIV from the brain. Probenecid acting as an adjuvant increases tenofovir concentrations in plasma and the kidneys thereby enhancing its therapeutic effect. However, the probenecid effect on brain tenofovir concentration and possible adverse effects remains poorly understood. We investigated the effect of probenecid co-administered tenofovir on tenofovir brain concentration, interleukin-1β (IL-1β) and dopamine concentration in the prefrontal cortex (PFC) and the cerebellum. Ninety-six male BALB/c mice were divided into four groups viz: a control group, Tenofovir disoproxil fumarate (TDF) treated, probenecid treated, and TDF + probenecid treated. We orally administered a single dose of TDF (5 mg/kg), and probenecid (8.3 mg/kg), and sacrificed six mice per group after 1 h, 4 h, and 6 h post-treatment to collect plasma, PFC, and cerebellar tissue. Co-administered tenofovir increased tenofovir concentration, peaking at 6 h with the cerebellum having the highest concentration. This suggests that probenecid enhanced the entry of tenofovir into the brain. Tenofovir alone increased IL-1β concentration at all intervals post-administration, while probenecid alone had no impact on IL-1β concentration. Co-administered tenofovir also increased IL-1β concentration. Probenecid’s limited impact on IL-1β concentration following co-administration suggests that its anti-inflammatory properties may require more than 6 h to have an effect. Furthermore, neither tenofovir nor probenecid affected dopamine concentration. In conclusion, probenecid enhances the concentration and retention of tenofovir in the brain, making it a possible pharmacokinetic enhancer. However, its anti-inflammatory effects may require a longer duration to fully manifest.

血脑屏障对替诺福韦的渗透性有限，限制了替诺福韦清除脑内艾滋病毒的能力。丙磺舒作为一种佐剂可增加血浆和肾脏中替诺福韦的浓度，从而增强其治疗效果。然而，人们对丙磺舒对脑内替诺福韦浓度的影响以及可能产生的不良反应仍知之甚少。我们研究了丙磺舒合用替诺福韦对替诺福韦脑浓度、白细胞介素-1β（IL-1β）以及前额叶皮层（PFC）和小脑多巴胺浓度的影响。96只雄性BALB/c小鼠被分为四组，即对照组、富马酸替诺福韦酯（TDF）治疗组、丙磺舒治疗组和TDF+丙磺舒治疗组。我们口服了单剂量的TDF（5毫克/千克）和丙磺舒（8.3毫克/千克），并在治疗后1小时、4小时和6小时后将每组6只小鼠处死，以收集血浆、全氟甲烷和小脑组织。合用替诺福韦增加了替诺福韦的浓度，在6小时达到峰值，小脑的浓度最高。这表明丙磺舒促进了替诺福韦进入大脑。在给药后的所有时间间隔内，单独服用替诺福韦都会增加IL-1β的浓度，而单独服用丙磺舒对IL-1β的浓度没有影响。同时服用替诺福韦也会增加IL-1β的浓度。丙磺舒在联合用药后对 IL-1β 浓度的影响有限，这表明其抗炎特性可能需要 6 小时以上才能发挥作用。此外，替诺福韦和丙磺舒都不会影响多巴胺的浓度。总之，丙磺舒可提高替诺福韦在大脑中的浓度和保留率，因此可能是一种药代动力学增强剂。不过，它的抗炎作用可能需要更长的时间才能充分体现出来。

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引用次数: 0

Hippocampal fimbria atrophy and its mediating effect between cerebral small vessel disease and cognitive impairment 海马体边缘萎缩及其在大脑小血管疾病与认知障碍之间的中介效应

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-24 DOI: 10.1016/j.neuroscience.2024.10.039

Na Wang , Jing Li , Xinyue Zhang , Yian Gao , Chaofan Sui , Nan Zhang , Yena Che , Changhu Liang , Lingfei Guo , Meng Li

We aimed to investigate the relationship between the volume reduction in hippocampal (HP) subregions and cognitive impairment in patients with cerebral small vessel disease (CSVD). Clinical, cognitive, and magnetic resonance imaging data were obtained for 315 participants. The CSVD group included 146 participants with a total CSVD score of 1–4. 169 participants with a total CSVD score of zero were used as control group (CSVD-0). The volume differences of 19 HP subregions between CSVD and CSVD–0 groups were analyzed, and we investigated the hazard factors that might cause subregional volume reduction in HP. Mediation analysis was performed to detect the relationship among HP subregional volumes, CSVD burden, and cognitive function. In our results, significant differences can be found in the volumes of CA4 body, presubiculum–head, presubiculum–body, subiculum–body, GC–ML–DG–head, GC–ML–DG–body, fimbria, and HP tail between CSVD group and control group. Regression analysis showed that fimbria was the most impacted HP subregion by CSVD. And mediation analysis revealed fimbria volume was a mediator variable between total CSVD score and MoCA/SCWT score. These results suggest that the volumes of HP subregions, especially the fimbria, may be effective potential biomarkers for early detecting cognitive impairment in CSVD.

我们旨在研究脑小血管疾病（CSVD）患者海马（HP）亚区体积缩小与认知障碍之间的关系。我们获得了 315 名参与者的临床、认知和磁共振成像数据。CSVD组包括146名CSVD总分1-4分的患者。169 名 CSVD 总分为零的参与者作为对照组（CSVD-0）。我们分析了CSVD组和CSVD-0组19个HP亚区的体积差异，并研究了可能导致HP亚区体积缩小的危险因素。我们还进行了中介分析，以检测HP亚区体积、CSVD负担和认知功能之间的关系。结果发现，CSVD组与对照组的CA4体、管前头、管前体、管下体、GC-ML-DG-头、GC-ML-DG-体、边缘和HP尾的体积存在明显差异。回归分析表明，边缘是受CSVD影响最大的HP亚区。中介分析显示，边缘区体积是 CSVD 总分和 MoCA/SCWT 分数之间的中介变量。这些结果表明，HP亚区（尤其是边缘区）的体积可能是早期检测CSVD患者认知功能障碍的有效潜在生物标志物。

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引用次数: 0

Exercise preconditioning mitigates Ischemia-Reperfusion injury in rats by enhancing mitochondrial respiration 运动预处理通过增强线粒体呼吸缓解大鼠缺血再灌注损伤

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-24 DOI: 10.1016/j.neuroscience.2024.10.045

Runyu Liang , Xinlei Hou , Daguo Zhou , Luwen Zhu , Lili Teng , Wenjing Song , Qiang Tang

Cerebral ischemia and subsequent reperfusion damage are prevalent in clinical practice, linked to numerous neurodegenerative diseases. Cerebral ischemia deprives brain tissue of essential oxygen and nutrients, disrupting energy metabolism and causing cellular dysfunction. Although reperfusion theoretically aids recovery, it instead initiates complex injury responses such as oxidative stress, apoptosis, and inflammation, worsening brain damage. Recent research suggests that enhancing neuronal energy status by modulating energy metabolism pathways can effectively counter these effects. For instance, boosting mitochondrial function, improving energy provision, and decreasing harmful metabolites can mitigate oxidative stress and cellular injury. This study investigated the protective effects of exercise preconditioning against ischemia–reperfusion injury in rats. It was observed that exercise enhances energy levels and mitochondrial respiration by upregulating the expression of COX4 and NAMPT proteins and activating AMPK and mitochondrial complex V. This process facilitates metabolic reprogramming characterized by the promotion of oxidative phosphorylation (OXPHOS) and the pentose phosphate pathway (PPP), alongside a reduction in glycolysis. Such reprogramming reduces harmful metabolites, mitigating apoptosis and oxidative stress, and is a key factor in alleviating acute ischemic hypoxia-induced brain damage. These findings introduce a novel therapeutic approach for ischemic brain reperfusion injury, underscoring the crucial role of ATP production and metabolic regulation in neuroprotection.

脑缺血和随后的再灌注损伤是临床上的常见病，与多种神经退行性疾病有关。脑缺血会剥夺脑组织必需的氧气和营养物质，破坏能量代谢，导致细胞功能障碍。虽然再灌注理论上有助于恢复，但它反而会引发复杂的损伤反应，如氧化应激、细胞凋亡和炎症，加重脑损伤。最新研究表明，通过调节能量代谢途径来增强神经元的能量状态，可以有效抵消这些影响。例如，增强线粒体功能、改善能量供应和减少有害代谢物可减轻氧化应激和细胞损伤。本研究调查了运动预处理对大鼠缺血再灌注损伤的保护作用。研究观察到，运动可通过上调 COX4 和 NAMPT 蛋白的表达、激活 AMPK 和线粒体复合物 V 来提高能量水平和线粒体呼吸，从而促进以促进氧化磷酸化（OXPHOS）和磷酸戊糖途径（PPP）以及减少糖酵解为特征的代谢重编程。这种重编程减少了有害代谢物，减轻了细胞凋亡和氧化应激，是减轻急性缺血缺氧引起的脑损伤的关键因素。这些发现为缺血性脑再灌注损伤引入了一种新的治疗方法，强调了 ATP 生成和代谢调节在神经保护中的关键作用。

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引用次数: 0

Alcohol augmentation of acrolein-mediated brain injury in blast-induced TBI 在爆炸引起的创伤性脑损伤中，酒精会加重丙烯醛介导的脑损伤。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-23 DOI: 10.1016/j.neuroscience.2024.10.036

引用次数: 0

EMG and SSVEP-based bimodal estimation of elbow angle trajectory 基于 EMG 和 SSVEP 的肘部角度轨迹双模态估算。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-23 DOI: 10.1016/j.neuroscience.2024.10.030

Fatemeh Davarinia, Ali Maleki

Detecting intentions and estimating movement trajectories in a human–machine interface (HMI) using electromyogram (EMG) signals is particularly challenging, especially for individuals with movement impairments. Therefore, incorporating additional information from other biological sources, potential discrete information in the movement, and the EMG signal can be practical. This study combined EMG and target information to enhance estimation performance during reaching movements. EMG activity of the shoulder and arm muscles, elbow angle, and the electroencephalogram signals of ten healthy subjects were recorded while they reached blinking targets. The reaching target was recognized by steady-state visual evoked potential (SSVEP). The selected target’s final angle and EMG were then mapped to the elbow angle trajectory. The proposed bimodal structure, which integrates EMG and final elbow angle information, outperformed the EMG-based decoder. Even under conditions of higher fatigue, the proposed structure provided better performance than the EMG decoder. Including additional information about the recognized reaching target in the trajectory model improved the estimation of the reaching profile. Consequently, this study’s findings suggest that bimodal decoders are highly beneficial for enhancing assistive robotic devices and prostheses, especially for real-time upper limb rehabilitation.

使用肌电图（EMG）信号在人机界面（HMI）中检测意图和估计运动轨迹尤其具有挑战性，对于有运动障碍的人来说更是如此。因此，将来自其他生物源的附加信息、运动中潜在的离散信息和 EMG 信号结合起来是非常实用的。本研究结合了 EMG 和目标信息，以提高伸手动作中的估计性能。研究记录了十名健康受试者在到达闪烁目标时肩部和手臂肌肉的肌电图活动、肘关节角度以及脑电信号。伸手目标由稳态视觉诱发电位（SSVEP）识别。然后将所选目标的最终角度和肌电图映射到肘部角度轨迹上。所提出的双模态结构整合了肌电图和最终肘角信息，其性能优于基于肌电图的解码器。即使在疲劳度较高的情况下，所提出的结构也比肌电图解码器的性能更好。在轨迹模型中加入有关识别到的伸手目标的额外信息，可改善对伸手轮廓的估计。因此，本研究的结果表明，双模解码器非常有利于增强辅助机器人设备和假肢，尤其是用于实时上肢康复。

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引用次数: 0

Thalamus and its functional connections with cortical regions contribute to complexity-dependent cognitive reasoning 丘脑及其与大脑皮层区域的功能联系有助于复杂性依赖性认知推理。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-23 DOI: 10.1016/j.neuroscience.2024.10.034

Yanqing Wang

The thalamus is crucial for supporting various cognitive behaviors due to its extensive connectivity with multiple cortical regions. However, the role of the thalamus and its functional connections with cortical regions in cognitive reasoning remains unclear, since previous research has mainly focused on cortical regions when studying the neural mechanisms underlying cognitive reasoning. To fill this knowledge gap, we utilized 7 T functional magnetic resonance imaging (fMRI) to study the activation patterns of the thalamus and its functional connections with cortical regions during cognitive reasoning task, while also examining how the complexity of reasoning tasks affects thalamic activation and functional connections with cortical regions. Our findings showed that cognitive reasoning processes are related to increased activation of the thalamus and its functional connections with a specific set of cortical regions, consisting of dorsolateral prefrontal cortex, inferior frontal sulcus, intraparietal sulcus, anterior cingulate cortex/presupplementary motor area, precuneus, and ventral medial prefrontal cortex. Moreover, the increase in relational complexity of the reasoning tasks led to a corresponding increase in thalamic activation and functional connectivity with cortical regions. Given the complex thalamus structure, including multiple distinct nuclei exhibiting specific functional connections with particular cortical regions, we used an atlas defined thalamic subdivisions based on its structural connectivity with different cortical regions. Our findings indicated that these different thalamic subregions not only exhibited distinct connectivity patterns with specific cortical regions during performance of cognitive reasoning, but also showed distinct connectivity patterns varied with task complexity. Overall, our study presents evidence of the thalamus’s role and its connections with cortical regions in supporting increasingly complex cognitive reasoning behavior, illuminating its contribution to higher-order cognitive functions, such as reasoning.

丘脑与多个大脑皮层区域有着广泛的联系，对支持各种认知行为至关重要。然而，丘脑及其与大脑皮层区域的功能连接在认知推理中的作用仍不清楚，因为以往的研究在研究认知推理的神经机制时主要集中在大脑皮层区域。为了填补这一知识空白，我们利用 7 T 功能磁共振成像（fMRI）研究了认知推理任务中丘脑的激活模式及其与皮层区域的功能连接，同时还考察了推理任务的复杂性如何影响丘脑的激活以及与皮层区域的功能连接。我们的研究结果表明，认知推理过程与丘脑的激活及其与一组特定皮质区域的功能连接的增加有关，这些皮质区域包括背外侧前额叶皮质、额下沟、顶内沟、前扣带回皮质/辅助运动区、楔前区和腹内侧前额叶皮质。此外，推理任务关系复杂性的增加也导致丘脑激活和与皮层区域功能连接的相应增加。由于丘脑结构复杂，包括多个不同的核团，与特定的皮层区域具有特定的功能连接，因此我们根据丘脑与不同皮层区域的结构连接使用图谱对丘脑进行了细分。我们的研究结果表明，在进行认知推理时，这些不同的丘脑亚区不仅与特定的皮层区域表现出不同的连接模式，而且随着任务复杂程度的变化也表现出不同的连接模式。总之，我们的研究证明了丘脑在支持日益复杂的认知推理行为中的作用及其与皮层区域的连接，阐明了丘脑对推理等高阶认知功能的贡献。

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引用次数: 0

The effects of chronic desipramine treatment on neurotrophin-3 in the brain of mice with selective depletion of CREB and CREM in noradrenergic neurons 去甲肾上腺素能神经元中的 CREB 和 CREM 选择性耗竭小鼠大脑中神经营养素-3 的慢性去甲肾上腺素治疗效果。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-22 DOI: 10.1016/j.neuroscience.2024.10.020

Katarzyna Rafa-Zabłocka, Irena Nalepa, Grzegorz Kreiner

The disturbances in neurotrophic support are thought to be one of the main causes of depression, which depend not only on the neurotrophins themselves but also on the molecules regulating their synthesis and effector functions. One such molecule is cAMP responsive element binding protein (CREB), which role in depression and antidepressant drugs mechanism of action has been extensively studied. However, CREB’s effects vary depending on brain structure, necessitating specific transgenic models for studying its function. Moreover, deletion of CREB enhances cAMP response element modulator (CREM) expression, suspected to compensate for CREB in its absence.

Previously, mice lacking CREB in noradrenergic neurons and CREM (Creb1^DbhCreCrem-/-) showed to be insensitive to acute desipramine, whereas mice lacking only CREB (Creb1^DbhCre) showed similar effects as wild type animals (w/t). As neurotrophic changes require chronic antidepressant treatment, in current study mice (w/t, Creb1^DbhCre and Creb1^DbhCreCrem-/-; both males and females) were given desipramine for 21 days, to assess the effects of the drug on CREB, neurotrophins and their receptors in the hippocampus and prefrontal cortex.

Interestingly, desipramine had no effect on CREB in neither of studied groups. However, both male and female mice lacking CREB and CREM displayed alterations in neurotrophin-3 (NTF3) expression or protein levels, modulated by desipramine. These findings suggest NTF3 is connected with inhibited response to acute and probably chronic desipramine administration in Creb1^DbhCreCrem–/– mice, although in w/t chronic desipramine had no effect on NTF3. Nevertheless, our findings give insight into the role of non-BDNF neurotrophins in the mechanism of antidepressant drugs.

神经营养支持紊乱被认为是抑郁症的主要原因之一，这不仅取决于神经营养素本身，还取决于调节其合成和效应功能的分子。其中一种分子是 cAMP 反应元件结合蛋白（CREB），它在抑郁症和抗抑郁药物作用机制中的作用已被广泛研究。然而，CREB 的作用因大脑结构而异，因此需要特定的转基因模型来研究其功能。此外，CREB的缺失会增强cAMP反应元件调节器（CREM）的表达，疑似在CREB缺失时对其进行补偿。此前，在去甲肾上腺素能神经元中缺乏 CREB 和 CREM 的小鼠（Creb1DbhCreCrem-/-）显示对急性地西泮不敏感，而仅缺乏 CREB 的小鼠（Creb1DbhCre）显示出与野生型动物（w/t）相似的效果。由于神经营养的变化需要长期的抗抑郁治疗，在目前的研究中，给小鼠（w/t、Creb1DbhCre和Creb1DbhCreCrem-/-雌雄小鼠）服用地西泮21天，以评估药物对CREB、神经营养素及其在海马和前额叶皮层受体的影响。有趣的是，地西帕明对两组小鼠的CREB均无影响。然而，缺乏CREB和CREM的雄性和雌性小鼠的神经营养素-3（NTF3）表达或蛋白水平都会受到地西泮的影响。这些研究结果表明，在Creb1DbhCreCrem-/-小鼠中，NTF3与抑制对急性和可能慢性地西帕明给药的反应有关，尽管在w/t小鼠中，慢性地西帕明对NTF3没有影响。尽管如此，我们的研究结果让我们了解到非 BDNF 神经营养素在抗抑郁药物机制中的作用。

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引用次数: 0

The presence of drum and bass modulates responses in the auditory dorsal pathway and mirror-related regions to pop songs 鼓和低音的存在会调节听觉背侧通路和镜像相关区域对流行歌曲的反应。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-22 DOI: 10.1016/j.neuroscience.2024.10.024

Chia-Wei Li , Chen-Gia Tsai

In pop music, drum and bass components are crucial for generating the desire to move one’s body, primarily due to their role in delivering salient metrical cues. This study explored how the presence of drum and bass influences neural responses to unfamiliar pop songs. Using AI-based algorithms, we isolated the drum and bass components from the musical excerpts, creating two additional versions: one that included only the drum and bass (excluding vocals and other instruments), and another that excluded the drum and bass (consisting solely of vocals and other instruments). Twenty-five participants were subjected to fMRI scans while listening to these musical stimuli. Analysis of fMRI data indicated that the removal of drum and bass led to increased activity in the auditory dorsal pathway, suggesting that the absence of these metrical cues demands greater cognitive effort to process the beats. In contrast, the version featuring only drum and bass elicited stronger activation in frontal regions associated with mirror properties, including the right ventral premotor cortex (extending into the inferior frontal gyrus) and left dorsolateral prefrontal cortex, compared to the original version. Overall, this study contributed insights into the foundational role of drum and bass in imparting metrical salience to pop songs, enriching our understanding of listeners’ sensorimotor processing of musical genres that prominently feature these two elements.

在流行音乐中，鼓和低音部分对于产生移动身体的欲望至关重要，这主要是由于它们在提供突出的节拍线索方面所起的作用。本研究探讨了鼓和低音的存在如何影响神经对陌生流行歌曲的反应。我们使用基于人工智能的算法，从音乐选段中分离出了鼓和低音成分，并创建了两个额外的版本：一个版本只包括鼓和低音（不包括人声和其他乐器），另一个版本不包括鼓和低音（只包括人声和其他乐器）。25 名参与者在聆听这些音乐刺激时接受了 fMRI 扫描。对 fMRI 数据的分析表明，去掉鼓和低音会导致听觉背侧通路的活动增加，这表明缺少这些节拍线索需要更大的认知努力来处理节拍。相反，与原始版本相比，只有鼓和低音的版本在与镜像特性相关的额叶区域引起了更强的激活，包括右侧腹侧前运动皮层（延伸到额叶下回）和左侧背外侧前额叶皮层。总之，这项研究有助于我们深入了解鼓和低音在赋予流行歌曲节拍显著性方面的基础性作用，从而丰富我们对听众对以这两种元素为显著特征的音乐类型的感觉运动处理的理解。

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