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Differential expression and significance of cytokines in cerebrospinal fluid of patients with viral encephalitis 病毒性脑炎患者脑脊液中细胞因子的不同表达及其意义。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-09 DOI: 10.1016/j.neuroscience.2024.10.014

To extensively identify cerebrospinal fluid (CSF) cytokine profiles related to the occurrence, development and prognosis of viral encephalitis (VE) patients by using a high-throughput proteomic approach.

We measured 80 cytokines in the CSF of acute-phase VE patients (n = 11) using high-throughput protein chip technology, comparing them to controls (n = 6). ELISA validated these findings and assessed additional cytokines from prior literature in a larger cohort (15 VE patients, 15 controls). Correlations between biomarkers and clinical characteristics were also examined.

In the initial stage, we identified two differentially expressed cytokines: cathepsin-L (CTSL), which was up-regulated, and Fractalkine, which was down-regulated. Functional enrichment analysis revealed that these proteins are linked to inflammation, apoptosis, autophagy, and blood-brain barrier disruption. In stage2, the elevations of cathepsin-L (CTSL), fractalkine, interleukin-6 (IL-6), IL-1β, macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), insulin-like growth factor Ⅱ (IGF-2) and CXC chemokine ligand 10 (CXCL10) in VE were validated by ELISA. The results of linear regression indicated that these cytokines was positively correlated with CSF reactive lesions (p < 0.05).

In this study, some biomarkers related with CSF level changes and prognosis were obtained. Although these cytokines are not specific, they may be related to the occurrence and development of VE. CTSL, MIF, IL-1β, TNF-α and CXCL10 can be used as VE potential biomarkers. These cytokines may participate in the pathogenesis of VE through inflammatory response, cell apoptosis, autophagy, blood-brain barrier disruption and cytokine-cytokine receptor interaction pathway.

利用高通量蛋白质组学方法广泛鉴定与病毒性脑炎（VE）患者的发生、发展和预后相关的脑脊液（CSF）细胞因子谱。我们利用高通量蛋白芯片技术测量了急性期 VE 患者（n = 11）脑脊液中的 80 种细胞因子，并将其与对照组（n = 6）进行了比较。ELISA 验证了这些发现，并在一个更大的队列（15 名 VE 患者，15 名对照组）中评估了先前文献中的其他细胞因子。我们还研究了生物标志物与临床特征之间的相关性。在最初阶段，我们发现了两种表达不同的细胞因子：上调的 cathepsin-L (CTSL) 和下调的 Fractalkine。功能富集分析表明，这些蛋白与炎症、细胞凋亡、自噬和血脑屏障破坏有关。在第二阶段，通过酶联免疫吸附试验（ELISA）验证了 VE 中的 cathepsin-L (CTSL)、fractalkine、白细胞介素-6 (IL-6)、IL-1β、巨噬细胞迁移抑制因子 (MIF)、肿瘤坏死因子-α (TNF-α)、胰岛素样生长因子 Ⅱ (IGF-2) 和 CXC 趋化因子配体 10 (CXCL10)的升高。线性回归结果表明，这些细胞因子与 CSF 反应性病变呈正相关（p

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引用次数: 0

Astrocytes contribute to the functional differentiation of the hippocampal longitudinal axis during reward and aversion processing in the adult male rat 在成年雄鼠的奖赏和厌恶加工过程中，星形胶质细胞有助于海马纵轴的功能分化。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-05 DOI: 10.1016/j.neuroscience.2024.10.011

This study aims to investigate whether glial cells, in particular putative astrocytes, contribute to functional distinctions between the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus. To evaluate this, we performed three different behavioral tasks (i.e., Morris water maze; MWM, Passive avoidance; PA, T-maze place preference; TPP) to determine whether the DH, IH, and VH are necessary for each task. Sensitivity of behavioral tasks was confirmed using lidocaine (2 %, 1 μl) reversible inactivation. Subsequently, we examined the effects of silencing astrocytes, using fluorocitrate (FC, 1 mM/1 μl), into the DH, IH, and VH on these tasks. The effects of drugs were examined separately. We observed that injection of FC into the DH resulted in a significant impairment in MWM performance. In contrast, while FC injections into the IH or VH did not prevent platform localization during the acquisition phase, rats showed difficulty recalling the target zone during the retrieval phase. In the PA test, FC injection into the VH impaired task learning and memory. During the acquisition phase, FC injection into the DH or IH did not differ from the control in the number of shocks; however, during retrieval, there was a significant decrease in the latency before entering the dark chamber. The TPP test performance was impaired by FC injection in the IH. In sum, we show that glial cells, especially astrocytes in specific functional regions of the hippocampus, play distinct roles in processing aversive and rewarding experiences and contribute to the functional organization of the hippocampal longitudinal axis.

本研究旨在探讨神经胶质细胞（尤其是假定星形胶质细胞）是否有助于区分背侧（DH）、中间（IH）和腹侧（VH）海马的功能。为了评估这一点，我们进行了三种不同的行为任务（即莫里斯水迷宫（Morris water maze; MWM）、被动回避（Passive avoidance; PA）和T迷宫位置偏好（T-maze place preference; TPP）），以确定DH、IH和VH是否为每种任务所必需。利多卡因（2 %，1 μl）可逆性失活证实了行为任务的敏感性。随后，我们使用柠檬酸氟（FC，1 mM/1 μl）检测了在 DH、IH 和 VH 中沉默星形胶质细胞对这些任务的影响。我们对药物的影响进行了单独研究。我们观察到，向 DH 注射 FC 会导致 MWM 成绩明显下降。相反，虽然向 IH 或 VH 注射 FC 并不妨碍大鼠在习得阶段进行平台定位，但大鼠在检索阶段却很难回忆起目标区域。在 PA 测试中，向 VH 注射 FC 会损害任务学习和记忆。在获得阶段，向DH或IH注射FC在冲击次数上与对照组没有差异；但在检索阶段，大鼠进入暗室前的潜伏期显著缩短。在 IH 注射 FC 会影响 TPP 测试成绩。总之，我们的研究表明，神经胶质细胞，尤其是海马特定功能区的星形胶质细胞，在处理厌恶和奖励体验时发挥着不同的作用，并对海马纵轴的功能组织做出了贡献。

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引用次数: 0

Neurophysiological measures of covert semantic processing in neurotypical adolescents actively ignoring spoken sentence inputs: A high-density event-related potential (ERP) study 神经畸形青少年主动忽略口语句子输入时隐蔽语义处理的神经生理学测量：高密度事件相关电位（ERP）研究。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-05 DOI: 10.1016/j.neuroscience.2024.10.008

Language comprehension requires semantic processing of individual words and their context within a sentence. Well-characterized event-related potential (ERP) components (the N400 and late positivity component (LPC/P600)) provide neuromarkers of semantic processing, and are robustly evoked when semantic errors are introduced into sentences. These measures are useful for evaluating semantic processing in clinical populations, but it is not known whether they can be evoked in more severe neurodevelopmental disorders where explicit attention to the sentence inputs cannot be objectively assessed (i.e., when sentences are passively listened to). We evaluated whether N400 and LPC/P600 could be detected in adolescents who were explicitly ignoring sentence inputs. Specifically, it was asked whether explicit attention to spoken inputs was required for semantic processing, or if a degree of automatic processing occurs when the focus of attention is directed elsewhere? High-density ERPs were acquired from twenty-two adolescents (12–17 years), under two experimental conditions: 1. individuals actively determined whether the final word in a sentence was congruent or incongruent with sentence context, or 2. passively listened to background sentences while watching a video. When sentences were ignored, N400 and LPC/P600 were robustly evoked to semantic errors, albeit with reduced amplitudes and protracted/delayed latencies. Statistically distinct topographic distributions during passive versus active paradigms pointed to distinct generator configurations for semantic processing as a function of attention. Covert semantic processing continues in neurotypical adolescents when explicit attention is withdrawn from sentence inputs. As such, this approach could be used to objectively investigate semantic processing in populations with communication deficits.

语言理解需要对单个单词及其在句子中的上下文进行语义处理。特征明确的事件相关电位（ERP）成分（N400 和晚期阳性成分 (LPC/P600)）提供了语义处理的神经标记，当句子中出现语义错误时，它们会被强烈唤起。这些指标可用于评估临床人群的语义处理能力，但在无法客观评估对句子输入的明确注意的情况下（即被动聆听句子时），这些指标是否能唤起更严重的神经发育障碍患者的注意，目前尚不清楚。我们评估了在明确忽略句子输入的青少年中是否能检测到 N400 和 LPC/P600。具体来说，我们要问的是，语义处理是否需要明确注意口语输入，或者当注意力转向别处时，是否会发生一定程度的自动处理？在两种实验条件下，对 22 名青少年（12-17 岁）进行了高密度 ERP 采集：1. 青少年主动判断句子中的最后一个词与句子上下文是否一致；或 2. 青少年在观看视频时被动聆听背景句子。当句子被忽略时，N400 和 LPC/P600 对语义错误有很强的诱发作用，尽管振幅减小，潜伏期延长/延迟。在被动与主动范式中，统计上不同的拓扑分布表明，语义处理的不同发生器配置是注意力的函数。当显性注意从句子输入中撤出时，神经畸形青少年的隐蔽语义处理仍在继续。因此，这种方法可用于客观研究交流障碍人群的语义处理。

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引用次数: 0

The elevated open platform stress suppresses excitatory synaptic transmissionin the layer V anterior cingulate cortex. 开放平台压力的升高抑制了第 V 层前扣带回皮层的兴奋性突触传递。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-05 DOI: 10.1016/j.neuroscience.2024.10.009

Ryo Kawabata, Ayumi Fujita, Yoshihiko Oke, Ikuko Yao, Kohei Koga

There are various forms of stress including; physical, psychological and social stress. Exposure to physical stress can lead to physical sensations (e.g. hyperalgesia) and negative emotions including anxiety and depression in animals and humans. Recently, our studies in mice have shown that acute physical stress induced by the elevated open platform (EOP) can provoke long-lasting mechanical hypersensitivity. This effect appears to be related to activity in the anterior cingulate cortex (ACC) at the synaptic level. Indeed, EOP exposure induces synaptic plasticity in layer II/III pyramidal neurons from the ACC. However, it is still unclear whether or not EOP exposure alters intrinsic properties and synaptic transmission in layer V pyramidal neurons. This is essential because these neurons are known to be a primary output to subcortical structures which may ultimately impact the behavioral stress response. Here, we studied both intrinsic properties and excitatory/inhibitory synaptic transmission by using whole-cell patch-clamp method in brain slice preparations. The EOP exposure did not change intrinsic properties including resting membrane potentials and action potentials. In contrast, EOP exposure suppressed the frequency of miniature and spontaneous excitatory synaptic transmission with an alteration of kinetics of AMPA/GluK receptors. EOP exposure also reduced evoked synaptic transmission induced by electrical stimulation. Furthermore, we investigated projection-selective responses of the mediodorsal thalamus to the layer V ACC neurons. EOP exposure produced short-term depression in excitatory synaptic transmission on thalamo-ACC projections. These results suggest that the EOP stress provokes abnormal excitatory synaptic transmission in layer V pyramidal neurons of the ACC.

压力有多种形式，包括生理压力、心理压力和社会压力。暴露在物理压力下会导致动物和人类的身体感觉（如痛觉过敏）和负面情绪，包括焦虑和抑郁。最近，我们在小鼠身上进行的研究表明，高架开放平台（EOP）诱发的急性身体压力可引起持久的机械过敏。这种效应似乎与前扣带回皮层（ACC）在突触水平上的活动有关。事实上，EOP 暴露会诱导 ACC II/III 层锥体神经元的突触可塑性。但是，EOP 是否会改变第五层锥体神经元的突触传递，目前仍不清楚。这一点至关重要，因为众所周知，这些神经元是皮层下结构的主要输出，而皮层下结构最终可能会影响行为应激反应。在这里，我们采用全细胞膜片钳法在脑片制备物中研究了神经元的内在特性和兴奋/抑制性突触传递。暴露于 EOP 不会改变包括静息膜电位和动作电位在内的内在特性。相反，EOP抑制了微型和自发兴奋性突触传递的频率，改变了AMPA/GluK受体的动力学。EOP 还减少了电刺激诱发的突触传递。此外，我们还研究了丘脑内侧对第 V 层 ACC 神经元的投射选择性反应。EOP 对丘脑-ACC 投射的兴奋性突触传递产生了短期抑制。这些结果表明，EOP 引起的急性应激会导致 ACC 第 V 层锥体神经元的兴奋性突触传递异常。

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引用次数: 0

Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models 传统和条件基因敲除小鼠模型揭示了 Snf7-3 在突触功能和认知行为中的关键作用。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-05 DOI: 10.1016/j.neuroscience.2024.10.010

Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a “Knockout-first” strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25–40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8–24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.

Snf7-3是内溶酶体分拣运输（ESCRT）途径所需的内溶酶体分拣复合物的重要组成部分，在内溶酶体功能中发挥着至关重要的作用。为了阐明Snf7-3在体内的作用，我们采用 "基因敲除优先 "策略建立了常规样和条件性Snf7-3基因敲除（KO）小鼠模型。传统型Snf7-3 KO小鼠的Snf7-3 mRNA表达量明显减少，年龄较大的小鼠（25-40周）表现出社交识别能力受损和微型兴奋突触后电流（mEPSCs）增加。相反，8-24 周龄的条件性 KO 小鼠在前脑兴奋神经元中特异性地删除了 Snf7-3，表现出物体位置记忆受损和 mEPSC 频率升高。在这些小鼠的内侧前额叶皮层中观察到树突复杂性增强，表明早期突触紊乱。我们的发现强调了 Snf7-3 在维持正常认知功能和社会行为中的关键作用。在常规类KO小鼠和条件性KO小鼠中观察到的突触和行为缺陷突显了Snf7-3在特定神经元群中的重要性，表明早期突触变化可能先于更明显的认知障碍。

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引用次数: 0

Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury. 爆炸诱发创伤性脑损伤小鼠模型中受伤后饮酒的时间差异效应。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-05 DOI: 10.1016/j.neuroscience.2024.10.003

Zaiyang Zhang, Tiange Xiao, Mekyna R Hall, Jennifer S Crodian, Anna K Alford, Adam Kimbrough, Riyi Shi

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

创伤性脑损伤是一种影响全球数百万人的常见疾病，但目前尚无明确的认识或有效的治疗方法。军人遭受爆炸引起的创伤性脑损伤（bTBI）的风险很高。此外，饮酒在这一人群中很常见，研究表明，创伤性脑损伤后饮酒可导致记忆力减退。因此，酒精有可能导致脑外伤的整体病理结果。然而，这种可能性尚未得到详细探讨。在此，我们将轻度脑损伤（mbTBI）模型与黑暗中饮酒（DID）范式相结合，通过检测小鼠脑氧化应激水平和行为改变，研究mbTBI与饮酒之间的病理协同作用。结果显示，在mbTBI后的早期时间点，创伤后饮酒具有抗焦虑和改善短期记忆的作用。然而，颅脑损伤后长达三周的长期饮酒会损害长期记忆，并伴随着与记忆和焦虑相关的脑区氧化应激的加剧。这些研究结果以及之前的体外创伤性脑损伤/酒精研究结果表明，物理力量和撞击后酒精暴露会产生病理协同作用。这些知识可能有助于为创伤性脑损伤患者制定指导原则，以避免他们的大脑受到进一步伤害，并帮助他们在创伤性脑损伤后最大限度地恢复。

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引用次数: 0

Negative allosteric modulator of Group Ⅰ mGluRs: Recent advances and therapeutic perspective for neuropathic pain mGluRs Ⅰ类负变构调节剂：神经病理性疼痛的最新进展和治疗前景。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-04 DOI: 10.1016/j.neuroscience.2024.10.004

Neuropathic pain (NP) is a widespread public health problem that existing therapeutic treatments cannot manage adequately; therefore, novel treatment strategies are urgently required. G-protein-coupled receptors are important for intracellular signal transduction, and widely participate in physiological and pathological processes, including pain perception. Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are predominantly implicated in central sensitization, which can lead to hyperalgesia and allodynia. Many orthosteric site antagonists targeting Group I mGluRs have been found to alleviate NP, but their poor efficacy, low selectivity, and numerous side effects limit their development in NP treatment. Here we reviewed the advantages of Group I mGluRs negative allosteric modulators (NAMs) over orthosteric site antagonists based on allosteric modulation mechanism, and the challenges and opportunities of Group I mGluRs NAMs in NP treatment. This article aims to elucidate the advantages and future development potential of Group I mGluRs NAMs in the treatment of NP.

神经病理性疼痛（NP）是一个普遍存在的公共健康问题，现有的治疗方法无法对其进行有效控制；因此，迫切需要新的治疗策略。G 蛋白偶联受体对细胞内的信号转导非常重要，广泛参与生理和病理过程，包括痛觉。I 组代谢型谷氨酸受体（mGluRs），包括 mGluR1 和 mGluR5，主要与中枢敏化有关，可导致痛觉减退和异动症。已发现许多针对 I 组 mGluRs 的正交部位拮抗剂可减轻 NP，但其疗效差、选择性低和副作用多，限制了它们在 NP 治疗中的发展。本文综述了基于异位调节机制的 I 组 mGluRs 负性异位调节剂（NAMs）相对于正位拮抗剂的优势，以及 I 组 mGluRs NAMs 在 NP 治疗中面临的挑战和机遇。本文旨在阐明 I 组 mGluRs NAMs 在治疗 NP 方面的优势和未来发展潜力。

引用次数: 0

Mendelian randomization in Alzheimer’s disease and mild cognitive impairment: Hippocampal volume associations 阿尔茨海默病和轻度认知障碍的孟德尔随机化：海马体积关联

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-04 DOI: 10.1016/j.neuroscience.2024.10.007

This study investigates the association between cognitive dysfunction and hippocampal volumes in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) using Mendelian randomization. A meta-analysis of 503 healthy controls, 562 MCI patients, and 389 CE patients revealed significant reductions in hippocampal and subregion volumes in MCI and AD compared to controls. While various subregions showed volume reductions, no causal relationship between hippocampal volume and AD was established through Mendelian randomization analysis. In conclusion, significant volume reductions were observed in MCI and AD patients, highlighting the complexity of the relationship between hippocampal volume and cognitive impairment.

本研究采用孟德尔随机法研究了阿尔茨海默病（AD）和轻度认知障碍（MCI）患者认知功能障碍与海马体积之间的关系。对503名健康对照组、562名MCI患者和389名CE患者进行的荟萃分析表明，与对照组相比，MCI和AD患者的海马体积和亚区体积显著减少。虽然不同亚区的体积都有所减少，但通过孟德尔随机分析，海马体积与AD之间并没有因果关系。总之，在MCI和AD患者中观察到了明显的体积减少，突出了海马体积与认知障碍之间关系的复杂性。

引用次数: 0

Tissue nonspecific alkaline phosphatase deficiency impairs Purkinje cell development and survival in a mouse model of infantile hypophosphatasia 组织非特异性碱性磷酸酶缺乏症会损害小鼠模型中的浦肯野细胞发育和存活。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-04 DOI: 10.1016/j.neuroscience.2024.10.005

Loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP) gene can result in hypophosphatasia (HPP), an inherited multi-systemic metabolic disorder that is well-known for skeletal and dental hypomineralization. However, emerging evidence shows that both adult and pediatric patients with HPP suffer from cognitive deficits, higher measures of depression and anxiety, and impaired sensorimotor skills. The cerebellum plays an important role in sensorimotor coordination, cognition, and emotion. To date, the impact of TNAP mutation on the cerebellar circuitry development and function remains poorly understood. The main objective of this study was to investigate the roles of TNAP in cerebellar development and function, with a particular focus on Purkinje cells, in a mouse model of infantile HPP. Male and female wild type (WT) and TNAP knockout (KO) mice underwent behavioral testing on postnatal day 13–14 and were euthanized after completion of behavioral tests. Cerebellar tissues were harvested for gene expression and immunohistochemistry analyses. We found that TNAP mutation resulted in significantly reduced body weight, shorter body length, and impaired sensorimotor functions in both male and female KO mice. These developmental and behavioral deficits were accompanied by abnormal Purkinje cell morphology and dysregulation of genes that regulates synaptic transmission, cellular growth, proliferation, and death. In conclusion, inactivation of TNAP via gene deletion causes developmental delays, sensorimotor impairment, and Purkinje cell maldevelopment. These results shed light on a new perspective of cerebellar dysfunction in HPP.

组织非特异性碱性磷酸酶（TNAP）基因的功能缺失突变可导致低磷血症（HPP），这是一种遗传性多系统代谢疾病，以骨骼和牙齿矿化度低而闻名。然而，新的证据显示，成人和儿童 HPP 患者都存在认知障碍、抑郁和焦虑程度较高以及感觉运动技能受损等问题。小脑在感觉运动协调、认知和情感方面发挥着重要作用。迄今为止，人们对 TNAP 基因突变对小脑回路发育和功能的影响仍知之甚少。本研究的主要目的是在婴儿HPP小鼠模型中研究TNAP在小脑发育和功能中的作用，尤其是对Purkinje细胞的作用。雌雄野生型（WT）和 TNAP 基因敲除（KO）小鼠在出生后第 13-14 天接受行为测试，并在行为测试结束后安乐死。采集小脑组织进行基因表达和免疫组化分析。我们发现，TNAP突变导致雄性和雌性KO小鼠体重明显降低，体长缩短，感觉运动功能受损。伴随这些发育和行为缺陷的是Purkinje细胞形态异常以及调节突触传递、细胞生长、增殖和死亡的基因失调。总之，通过基因缺失使 TNAP 失活会导致发育迟缓、感觉运动障碍和浦肯野细胞发育不良。这些结果从一个新的角度揭示了HPP的小脑功能障碍。

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引用次数: 0

Integration patterns of functional brain networks can predict the response to abdominal acupuncture in patients with major depressive disorder 大脑功能网络的整合模式可预测重度抑郁症患者对腹针疗法的反应。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2024-10-03 DOI: 10.1016/j.neuroscience.2024.10.002

Abdominal acupuncture has definite efficacy for major depressive disorder (MDD). Our study examined how abdominal acupuncture regulates the integration within and between brain networks of MDD patients by neuroimaging and whether this functional integration can predict the efficacy. Forty-six female MDD patients were randomly divided into a fluoxetine + real acupuncture group (n = 22) and a fluoxetine + sham acupuncture group (n = 24). The differences in functional magnetic resonance imaging data in the intra- and inter-network functional connectivity (FC) of the default mode network (DMN), affective network (AN), salience network (SN), and cognitive control network (CCN) between the two groups were analyzed. The FCs in brain regions with the inter-group differences and support vector regression were used to predict the efficacy of abdominal acupuncture. Our results showed: that the intra- and inter-network FCs of DMN, AN, SN, and CCN could be changed by abdominal acupuncture. Using the baseline FCs within AN and DMN or AN–DMN as characteristics, combined with support vector regression, could better predict the efficacy of acupuncture. Our study suggests that abdominal acupuncture could treat MDD by regulating the integration of the functional networks DMN, AN, SN, and CCN. The baseline FCs within the DMN and AN or between them could be used as neural markers for predicting the efficacy of abdominal acupuncture.

腹针对重度抑郁症（MDD）有确切疗效。我们的研究通过神经影像学检查了腹针如何调节重度抑郁症患者大脑网络内部和之间的整合，以及这种功能整合是否能预测疗效。46名女性MDD患者被随机分为氟西汀+真针灸组（22人）和氟西汀+假针灸组（24人）。分析了两组患者默认模式网络（DMN）、情感网络（AN）、显著性网络（SN）和认知控制网络（CCN）的网络内和网络间功能连接（FC）的功能磁共振成像数据差异。利用具有组间差异的脑区FC和支持向量回归来预测腹针的疗效。结果显示：腹部针灸可改变DMN、AN、SN和CCN的网络内和网络间FCs。以AN和DMN或AN-DMN内的基线FC为特征，结合支持向量回归，可以更好地预测针灸的疗效。我们的研究表明，腹针可以通过调节DMN、AN、SN和CCN功能网络的整合来治疗MDD。DMN和AN内部或之间的基线FC可作为预测腹针疗效的神经标记。

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引用次数: 0