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Endocrine disrupting effects on morphological synaptic plasticity 内分泌干扰对形态突触可塑性的影响
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 DOI: 10.1016/j.yfrne.2024.101157
Attila Zsarnovszky , Daiana Alymbaeva , Gergely Jocsak , Csaba Szabo , Boglárka Mária Schilling-Tóth , David Sandor Kiss
Neural regulation of the homeostasis depends on healthy synaptic function. Adaptation of synaptic functions to physiological needs manifests in various forms of synaptic plasticity (SP), regulated by the normal hormonal regulatory circuits. During the past several decades, the hormonal regulation of animal and human organisms have become targets of thousands of chemicals that have the potential to act as agonists or antagonists of the endogenous hormones. As the action mechanism of these endocrine disrupting chemicals (EDCs) came into the focus of research, a growing number of studies suggest that one of the regulatory avenues of hormones, the morphological form of SP, may well be a neural mechanism affected by EDCs. The present review discusses known and potential effects of some of the best known EDCs on morphological synaptic plasticity (MSP). We highlight molecular mechanisms altered by EDCs and indicate the growing need for more research in this area of neuroendocrinology.
神经对平衡的调节依赖于健康的突触功能。突触功能对生理需求的适应表现为各种形式的突触可塑性(SP),由正常的激素调节回路调节。在过去几十年中,动物和人类生物体的激素调节已成为数千种化学物质的目标,这些化学物质有可能成为内源性激素的激动剂或拮抗剂。随着这些干扰内分泌的化学品(EDCs)的作用机制成为研究的焦点,越来越多的研究表明,激素的调节途径之一,即 SP 的形态形式,很可能是一种受 EDCs 影响的神经机制。本综述讨论了一些最著名的 EDC 对形态突触可塑性(MSP)的已知和潜在影响。我们强调了被 EDCs 改变的分子机制,并指出在这一神经内分泌学领域越来越需要开展更多的研究。
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引用次数: 0
Melatonin and brain barriers: The protection conferred by melatonin to the blood-brain barrier and blood-cerebrospinal fluid barrier 褪黑素与脑屏障:褪黑激素对血脑屏障和血脑脊液屏障的保护作用
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 DOI: 10.1016/j.yfrne.2024.101158
Rafael Mineiro , Maria Rodrigues Cardoso , Ana Catarina Duarte , Cecília Santos , Jose Cipolla-Neto , Fernanda Gaspar do Amaral , Diana Costa , Telma Quintela
The blood–brain barrier and the blood-cerebrospinal fluid barrier separate the blood from brain tissue and cerebrospinal fluid. These brain barriers are important to maintain homeostasis and complex functions by protecting the brain from xenobiotics and harmful endogenous compounds. The disruption of brain barriers is a characteristic of neurologic diseases. Melatonin is a lipophilic hormone that is mainly produced by the pineal gland. The blood–brain barrier and the blood-cerebrospinal fluid barriers are melatonin-binding sites. Among the several melatonin actions, the most characteristic one is the regulation of sleep-wake cycles, melatonin has anti-inflammatory and antioxidant properties. Since brain barriers disruption can arise from inflammation and oxidative stress, knowing the influence of melatonin on the integrity of brain barriers is extremely important. Therefore, the objective of this review is to gather and discuss the available literature about the regulation of brain barriers by melatonin.
血脑屏障和血脑脊液屏障将血液与脑组织和脑脊液隔开。这些脑屏障通过保护大脑免受异生物体和有害内源性化合物的侵害,对维持体内平衡和复杂功能非常重要。破坏脑屏障是神经系统疾病的一个特征。褪黑激素是一种亲脂性激素,主要由松果体分泌。血脑屏障和血-脑脊液屏障是褪黑素的结合部位。在褪黑素的多种作用中,最有特色的作用是调节睡眠-觉醒周期,褪黑素具有抗炎和抗氧化特性。由于炎症和氧化应激可导致脑屏障破坏,因此了解褪黑激素对脑屏障完整性的影响极为重要。因此,本综述旨在收集和讨论有关褪黑激素调节脑屏障的现有文献。
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引用次数: 0
Brain alteration of autoimmune thyroid disease: Neuropsychiatric impact, neuroimaging insights, and neurobiological implications 自身免疫性甲状腺疾病的大脑改变:神经精神影响、神经影像学见解和神经生物学意义。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 DOI: 10.1016/j.yfrne.2024.101159
Qin Wei , Haiyang Zhang , Haixia Guan , Xuefei Song , Huifang Zhou
Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, characterized by thyroid function disorder and autoimmune imbalance. Previous studies have demonstrated the decreased quality of life and neuropsychiatric manifestations in AITD patients, including anxiety, depression, cognitive impairment and affective disorder. These problems also plague the euthyroid AITD patients. Advanced neuroimaging techniques were well carried out and employed as an explanatory instrument for the above intriguing phenomenon. In recent years, an increasing number of neuroimaging studies have reported that these neuropsychiatric manifestations are accompanied by significant structural and functional brain alterations in AITD patients, mainly involved in neurocognitive and emotional regions, despite the underlying neurobiological mechanism is still unclear. The existing studies suggest that the potential pathogenesis of the neuropsychiatric manifestations and brain alterations does not depend on a single factor, but may result from a combination of thyroid function dysfunction, metabolic disorders, dysregulated autoimmune and trans-synaptic degeneration.
自身免疫性甲状腺疾病(AITD)是最常见的器官特异性自身免疫性疾病,以甲状腺功能紊乱和自身免疫失衡为特征。以往的研究表明,自身免疫性甲状腺疾病患者的生活质量下降,并表现出神经精神症状,包括焦虑、抑郁、认知障碍和情感障碍。这些问题也困扰着甲状腺功能正常的AITD患者。先进的神经影像学技术得到了很好的应用,并被用来解释上述耐人寻味的现象。近年来,越来越多的神经影像学研究报告称,AITD 患者的这些神经精神表现伴随着明显的脑结构和功能改变,主要涉及神经认知和情感区域,尽管其潜在的神经生物学机制仍不清楚。现有研究表明,神经精神表现和大脑改变的潜在发病机制并不取决于单一因素,而可能是甲状腺功能障碍、代谢紊乱、自身免疫失调和跨突触变性等综合因素的结果。
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引用次数: 0
Effect of 5-alpha reductase inhibitors in animal models of Parkinson’s disease 5-α 还原酶抑制剂对帕金森病动物模型的影响。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-01 DOI: 10.1016/j.yfrne.2024.101156
Mélanie Bourque , Marc Morissette , Amandine Isenbrandt , Silvia Giatti , Roberto Cosimo Melcangi , Manolo Carta , Roberto Frau , Marco Bortolato , Denis Soulet , Thérèse Di Paolo
Parkinson’s disease (PD) is characterized by motor symptoms due to loss of brain dopamine and non-motor symptoms, including gastrointestinal disorders. Although there is no cure for PD, symptomatic treatments are available. L-Dopa is the gold standard PD therapy, but most patients develop dyskinesias (LID), which are challenging to manage. Amantadine is recognized as the most effective drug for LID, but its adverse effects limit the use in patients. Here we review how 5α-reductase inhibitors (5ARIs), drugs used to treat benign prostatic hyperplasia and alopecia, exhibit beneficial effects in PD animal models. 5ARIs show neuroprotective properties in brain and gut dopaminergic systems, and reduce dyskinesias in rodent model of PD. Additionally, the 5ARI finasteride dampened dopaminergic-induced drug gambling in PD patients. Neuroprotection and antidyskinetic activities of 5ARIs in animal models of PD suggest their potential repurposing in men with PD to address gut dysfunction, protect brain DA and inhibit dyskinesias.
帕金森病(Parkinson's disease,PD)的特征是因大脑多巴胺丧失而出现运动症状和非运动症状,包括胃肠功能紊乱。虽然帕金森病无法治愈,但可以对症治疗。左旋多巴是治疗帕金森氏症的金标准,但大多数患者会出现运动障碍(LID),难以控制。金刚烷胺被认为是治疗运动障碍最有效的药物,但其不良反应限制了它在患者中的使用。在此,我们回顾了用于治疗良性前列腺增生和脱发的 5α 还原酶抑制剂(5ARIs)是如何在帕金森氏症动物模型中显示出有益作用的。5ARIs 对大脑和肠道多巴胺能系统具有神经保护作用,并能减少啮齿类动物模型中的运动障碍。此外,5ARI 非那雄胺还能抑制帕金森病患者由多巴胺能引起的药物赌博。5ARIs在帕金森病动物模型中的神经保护和抗运动障碍活性表明,它们有可能被重新用于男性帕金森病患者,以解决肠道功能障碍、保护大脑多巴胺并抑制运动障碍。
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引用次数: 0
Is melanin-concentrating hormone in the medial preoptic area a signal for the decline of maternal care in late postpartum? 内侧视前区的黑色素浓缩激素是产后晚期母性关怀减少的信号吗?产妇行为中的 MCH。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.yfrne.2024.101155
Ming Li

This manuscript proposes that melanin-concentrating hormone (MCH) in the medial preoptic area (MPOA) is an neurochemical signal evolved to trigger the declining process of maternal care. MCH in the MPOA appears only after parturition and is progressively increased with the progression of lactation, while maternal behavior declines progressively. Intra-MPOA injection of MCH decreases active maternal responses. MCH is also highly responsive to infant characteristics and maternal condition. Behavioral changes induced by MCH in late postpartum period are conducive to the decline of infant-directed maternal behavior. The MPOA MCH system may mediate the maternal behavior decline by suppressing the maternal approach motivation and/or increasing maternal withdrawal via its inhibitory action onto the mesolimbic dopamine D1/D2 receptors and its stimulating action on serotonin 5-HT2C receptors in the ventral tegmental area. Research into the MCH maternal effects will enhance our understanding of the neurochemical mechanisms underlying the maternal behavior decline.

本手稿提出,内侧视前区(MPOA)中的黑色素浓缩激素(MCH)是一种神经化学信号,它的进化触发了母性关怀的衰退过程。MPOA 中的 MCH 在分娩后才出现,并随着哺乳期的进展而逐渐增加,而母性行为则逐渐减少。在 MPOA 内注射 MCH 会降低母体的主动反应。MCH 对婴儿特征和母体状况的反应也很强烈。产后晚期 MCH 引起的行为变化有利于婴儿引导的母性行为的下降。MPOA MCH 系统可能通过其对间叶多巴胺 D1/D2 受体的抑制作用和对腹侧被盖区血清素 5-HT2C 受体的刺激作用,抑制母性接近动机和/或增加母性退缩,从而介导母性行为的下降。对 MCH 母性效应的研究将加深我们对母性行为衰退的神经化学机制的理解。
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引用次数: 0
Astrogenesis in the hypothalamus: A life-long process contributing to the development and plasticity of neuroendocrine networks 下丘脑的星形成因:促进神经内分泌网络发展和可塑性的终生过程。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.yfrne.2024.101154
Ariane Sharif, Vincent Prevot

Astrocytes are now recognized as integral components of neural circuits, regulating their maturation, activity and plasticity. Neuroendocrinology has provided fertile ground for revealing the diverse strategies used by astrocytes to regulate the physiological and behavioural outcomes of neural circuit activity in response to internal and environmental inputs. However, the development of astrocytes in the hypothalamus has received much less attention than in other brain regions such as the cerebral cortex and spinal cord. In this review, we synthesize our current knowledge of astrogenesis in the hypothalamus across various life stages. A distinctive feature of hypothalamic astrogenesis is that it persists all throughout lifespan, and involves multiple cellular sources corresponding to radial glial cells during early development, followed by tanycytes, parenchymal progenitors and locally dividing astrocytes. Astrogenesis in the hypothalamus is closely coordinated with the maturation of hypothalamic neurons. This coordination is exemplified by recent findings in neurons producing gonadotropin-releasing hormone, which actively shape their astroglial environment during infancy to integrate functionally into their neural network and facilitate sexual maturation, a process vulnerable to endocrine disruption. While hypothalamic astrogenesis shares common principles with other brain regions, it also exhibits specific features in its dynamics and regulation, both at the inter- and intra-regional levels. These unique properties emphasize the importance of further exploration. Additionally, we discuss the experimental strategies used to assess astrogenesis in the hypothalamus and their potential bias and limitations. Understanding the mechanisms of hypothalamic astrogenesis throughout life will be crucial for comprehending the development and function of the hypothalamus under both physiological and pathological conditions.

星形胶质细胞现在被认为是神经回路不可或缺的组成部分,可调节神经回路的成熟、活动和可塑性。神经内分泌学为揭示星形胶质细胞根据内部和环境输入调节神经回路活动的生理和行为结果的各种策略提供了肥沃的土壤。然而,与大脑皮层和脊髓等其他脑区相比,下丘脑中星形胶质细胞的发育受到的关注要少得多。在这篇综述中,我们总结了目前我们对下丘脑各生命阶段星形胶质细胞发育的了解。下丘脑星形细胞发生的一个显著特点是它终生持续存在,并涉及多种细胞来源,包括发育早期的放射状胶质细胞,随后是澹细胞、实质祖细胞和局部分裂的星形细胞。下丘脑的星形胶质细胞形成与下丘脑神经元的成熟密切相关。最近对产生促性腺激素释放激素的神经元的研究结果就是这种协调的例证,这些神经元在婴儿期积极塑造其星形胶质细胞环境,以便在功能上融入其神经网络并促进性成熟,而这一过程很容易受到内分泌干扰。虽然下丘脑星形胶质细胞的形成与其他脑区有着共同的原理,但它在区域间和区域内的动态和调控方面也表现出特殊的特征。这些独特的特性强调了进一步探索的重要性。此外,我们还讨论了用于评估下丘脑星形成因的实验策略及其潜在的偏差和局限性。了解下丘脑终生星形发生的机制对于理解下丘脑在生理和病理条件下的发育和功能至关重要。
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引用次数: 0
Hypothalamic neurons fully or partially expressing the dopaminergic phenotype: development, distribution, functioning and functional significance. A review 完全或部分表达多巴胺能表型的下丘脑神经元:分布、功能和功能意义。综述。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-10 DOI: 10.1016/j.yfrne.2024.101153
Michael V. Ugrumov

The hypothalamus is a key link in neuroendocrine regulations, which are provided by neuropeptides and dopamine. Until the late 1980 s, it was believed that, along with peptidergic neurons, hypothalamus contained dopaminergic neurons. Over time, it has been shown that besides dopaminergic neurons expressing the dopamine transporter and dopamine-synthesizing enzymes − tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) − the hypothalamus contains neurons expressing only TH, only AADC, both enzymes or only dopamine transporter. The end secretory product of TH neurons is L-3,4-dihydroxyphenylalanine, while that of AADC neurons and bienzymatic neurons lacking the dopamine transporter is dopamine. During ontogenesis, especially in the perinatal period, monoenzymatic neurons predominate in the hypothalamic neuroendocrine centers. It is assumed that L-3,4-dihydroxyphenylalanine and dopamine are released into the neuropil, cerebral ventricles, and blood vessels, participating in the regulation of target cell differentiation in the perinatal period and the functioning of target cells in adulthood.

下丘脑是由神经肽和多巴胺调节神经内分泌的关键环节。直到 20 世纪 80 年代末,人们一直认为下丘脑中除了肽能神经元外,还有多巴胺能神经元。随着时间的推移,研究表明,除了表达多巴胺转运体和多巴胺合成酶--酪氨酸羟化酶(TH)和芳香族 L-氨基酸脱羧酶(AADC)--的多巴胺能神经元外,下丘脑还含有只表达 TH、只表达 AADC、两种酶或只表达多巴胺转运体的神经元。TH 神经元的最终分泌物是 L-3,4-二羟基苯丙氨酸,而 AADC 神经元和缺乏多巴胺转运体的生物酶神经元的最终分泌物是多巴胺。在胚胎发育过程中,尤其是在围产期,单酶神经元在下丘脑神经内分泌中枢中占主导地位。据推测,L-3,4-二羟基苯丙氨酸和多巴胺被释放到神经膜、脑室和血管中,参与调节围产期靶细胞的分化和成年期靶细胞的功能。
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引用次数: 0
The emerging role of rapid corticosteroid actions on excitatory and inhibitory synaptic signaling in the brain 皮质类固醇对大脑兴奋性和抑制性突触信号传递的快速作用。
IF 6.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-01 DOI: 10.1016/j.yfrne.2024.101146
Marian Joëls , Henk Karst , Jeffrey G. Tasker

Over the past two decades, there has been increasing evidence for the importance of rapid-onset actions of corticosteroid hormones in the brain. Here, we highlight the distinct rapid corticosteroid actions that regulate excitatory and inhibitory synaptic transmission in the hypothalamus, the hippocampus, basolateral amygdala, and prefrontal cortex. The receptors that mediate rapid corticosteroid actions are located at or close to the plasma membrane, though many of the receptor characteristics remain unresolved. Rapid-onset corticosteroid effects play a role in fast neuroendocrine feedback as well as in higher brain functions, including increased aggression and anxiety, and impaired memory retrieval. The rapid non-genomic corticosteroid actions precede and complement slow-onset, long-lasting transcriptional actions of the steroids. Both rapid and slow corticosteroid actions appear to be indispensable to adapt to a continuously changing environment, and their imbalance can increase an individual’s susceptibility to psychopathology.

过去二十年来,越来越多的证据表明,皮质类固醇激素在大脑中的快速作用非常重要。在此,我们重点介绍皮质类固醇在下丘脑、海马、杏仁核基底外侧和前额叶皮质中调节兴奋性和抑制性突触传递的独特快速作用。介导快速皮质类固醇作用的受体位于质膜或靠近质膜的位置,但许多受体的特征仍未得到明确。快速皮质类固醇效应在快速神经内分泌反馈和高级脑功能中发挥作用,包括增加攻击性和焦虑,以及损害记忆检索。皮质类固醇的快速非基因组作用先于类固醇的慢速持久转录作用,并与之互补。快速和缓慢的皮质类固醇作用似乎都是适应不断变化的环境所不可或缺的,它们的失衡会增加个体对精神病理学的易感性。
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引用次数: 0
Emotion recognition and regulation in males: Role of sex and stress steroids 男性的情绪识别和调节:性别和应激类固醇的作用
IF 7.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-09 DOI: 10.1016/j.yfrne.2024.101145
Erik Ilkevič , Markus Hausmann , Ramunė Grikšienė

Understanding emotions in males is crucial given their higher susceptibility to substance use, interpersonal violence, and suicide compared to females. Steroid hormones are assumed to be critical biological factors that affect and modulate emotion-related behaviors, together with psychological and social factors. This review explores whether males‘ abilities to recognize emotions of others and regulate their own emotions are associated with testosterone, cortisol, and their interaction. Higher levels of testosterone were associated with improved recognition and heightened sensitivity to threatening faces. In contrast, higher cortisol levels positively impacted emotion regulation ability. Indirect evidence from neuroimaging research suggested a link between higher testosterone levels and difficulties in cognitive emotion regulation. However, this notion must be investigated in future studies using different emotion regulation strategies and considering social status. The present review contributes to the understanding of how testosterone and cortisol affect psychological well-being and emotional behavior in males.

与女性相比,男性更容易使用药物、发生人际暴力和自杀,因此了解男性的情绪至关重要。类固醇激素被认为是影响和调节情绪相关行为的关键生物因素,同时也是心理和社会因素。本研究探讨了男性识别他人情绪和调节自身情绪的能力是否与睾酮、皮质醇及其相互作用有关。睾酮水平越高,识别能力越强,对威胁性面孔的敏感度也越高。相反,皮质醇水平越高,情绪调节能力越强。神经影像学研究的间接证据表明,睾酮水平较高与认知情绪调节困难之间存在联系。然而,这一观点必须在未来的研究中通过使用不同的情绪调节策略和考虑社会地位加以研究。本综述有助于了解睾酮和皮质醇如何影响男性的心理健康和情绪行为。
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引用次数: 0
Novel insights into the activating transcription factor 4 in Alzheimer’s disease and associated aging-related diseases: Mechanisms and therapeutic implications 激活转录因子 4 在阿尔茨海默氏症和相关衰老疾病中的新发现:机制和治疗意义
IF 7.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-24 DOI: 10.1016/j.yfrne.2024.101144
Nan Zhang , Jianfei Nao , Shun Zhang , Xiaoyu Dong

Ageing is inherent to all human beings, most mechanistic explanations of ageing results from the combined effects of various physiological and pathological processes. Additionally, aging pivotally contributes to several chronic diseases. Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding protein family, has recently emerged as a pivotal player owing to its indispensable role in the pathophysiological processes of Alzheimer’s disease and aging-related diseases. Moreover, ATF4 is integral to numerous biological processes. Therefore, this article aims to comprehensively review relevant research on the role of ATF4 in the onset and progression of aging-related diseases, elucidating its potential mechanisms and therapeutic approaches. Our objective is to furnish scientific evidence for the early identification of risk factors in aging-related diseases and pave the way for new research directions for their treatment. By elucidating the signaling pathway network of ATF4 in aging-related diseases, we aspire to gain a profound understanding of the molecular and cellular mechanisms, offering novel strategies for addressing aging and developing related therapeutics.

衰老是人类与生俱来的现象,大多数关于衰老的机理解释都是由各种生理和病理过程共同作用的结果。此外,衰老也是导致多种慢性疾病的关键因素。活化转录因子 4(ATF4)是 ATF/cAMP 反应元件结合蛋白家族的成员,由于其在阿尔茨海默病和衰老相关疾病的病理生理过程中扮演着不可或缺的角色,最近已成为一个关键角色。此外,ATF4 与许多生物过程密不可分。因此,本文旨在全面回顾 ATF4 在衰老相关疾病的发生和发展过程中所起作用的相关研究,阐明其潜在机制和治疗方法。我们的目的是为早期识别衰老相关疾病的风险因素提供科学依据,并为治疗这些疾病的新研究方向铺平道路。通过阐明 ATF4 在衰老相关疾病中的信号通路网络,我们希望深入了解其分子和细胞机制,为应对衰老和开发相关疗法提供新的策略。
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引用次数: 0
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Frontiers in Neuroendocrinology
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