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The association of late-life depressive symptoms with brain amyloid-β deposition: the ARIC-PET study 老年抑郁症状与脑淀粉样蛋白-β沉积的关系：ARIC-PET研究

IF 2.7 Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2025-01-01 Epub Date: 2025-10-30 DOI: 10.1016/j.nbas.2025.100152

Sylee Kanetkar , Valerie N. Morrill , Marco T. Egle , Keenan A. Walker , Dean F. Wong , Rebecca F. Gottesman

Late-life depression is associated with an increased risk of developing dementia related to Alzheimer’s disease, yet the mechanism underlying this relationship remains poorly understood. This study investigated the association of late-life depressive symptoms (LLDS) with brain amyloid deposition by PET. 334 dementia-free individuals from the Atherosclerosis Risk in Communities Study had Florbetapir-PET scans in late-life (ages 67–89). Elevated global and regional brain amyloid deposition was defined as a Florbetapir standardized uptake value ratio (SUVR) > 1.2. LLDS was assessed using the 11-item Center for Epidemiological Studies Depression Scale (CES-D) and defined as late-life CES-D ≥ 9. Several secondary depression measures (e.g., antidepressant use) were also explored. Stratified analyses across race, sex, and cognitive status groups were conducted. Participants (median age 76 years; 57.2 % female; 42.5 % Black; 26.9 % mild cognitive impairment) showed no association of LLDS with global amyloid deposition. Although antidepressant use was not associated with global amyloid overall, antidepressant use was associated with elevated global amyloid in individuals with normal cognition but not mild cognitive impairment. There was no effect modification by race and sex. Overall, our findings suggest that LLDS are generally not associated with global amyloid deposition, but further investigation of this relationship in larger sample sizes is warranted.

老年抑郁症与阿尔茨海默病相关的痴呆风险增加有关，但这种关系背后的机制尚不清楚。本研究通过PET研究了老年抑郁症状（LLDS）与脑淀粉样蛋白沉积的关系。来自社区动脉粥样硬化风险研究的334名无痴呆患者在晚年（67-89岁）进行了Florbetapir-PET扫描。升高的整体和区域脑淀粉样蛋白沉积被定义为Florbetapir标准化摄取值比（SUVR） > 1.2。LLDS采用11项流行病学研究中心抑郁量表（CES-D）进行评估，并定义为晚年CES-D≥9。还探讨了几种继发性抑郁措施（例如，使用抗抑郁药）。进行了跨种族、性别和认知状态组的分层分析。参与者（中位年龄76岁；57.2%女性；42.5%黑人；26.9%轻度认知障碍）显示LLDS与整体淀粉样蛋白沉积没有关联。虽然抗抑郁药的使用与总体淀粉样蛋白无关，但在认知正常而非轻度认知障碍的个体中，抗抑郁药的使用与总体淀粉样蛋白升高有关。没有种族和性别的影响。总的来说，我们的研究结果表明，LLDS通常与整体淀粉样蛋白沉积无关，但需要在更大的样本量中进一步研究这种关系。

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引用次数: 0

Nigrostriatal dopaminergic neurotransmission and resilience to peripheral systemic risk factors for gait slowing upon transition to uneven surfaces in older adult 黑质纹状体多巴胺能神经传递和对周围系统危险因素的恢复能力在老年人过渡到不平整的表面时步态减慢

IF 1.7 Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2025-01-01 Epub Date: 2025-06-20 DOI: 10.1016/j.nbas.2025.100143

Lana M. Chahine , Andrea Rosso , Ian Troidl , Mary Ganguli , Anne Newman , Steven Cummings , Stephanie Studenski , Brian Lopresti , Sarah Royse , Theodore Huppert , Mark Redfern , Patrick J. Sparto , Nico I. Bohnen , Caterina Rosano

Identifying mechanisms that compensate for slow gait speed in older adults is crucial. Dopaminergic neurotransmission curbs deleterious associations of cerebrovascular disease with gait, but whether it compensates for peripheral systemic risk factors (PSRF) for gait slowing has not been studied. In this cross-sectional study of community-dwelling older adults, we examined the relationship between nigrostriatal dopaminergic terminal integrity and gait speed in individuals with and without ≥ 1 PSRF for gait slowing: obesity, joint pain, or reduced muscle strength. The primary outcome was gait speed cost (%GSC) on transition from even to uneven surface. Participants underwent dopaminergic imaging with dihydrotetrabenazine [¹¹C]DTBZ positron emission tomography. Among 197 individuals, (mean (SD) age 74.92 (4.53) years; 61.93 % female; 90.86 % White), 130 (65.99 %) had ≥ 1 PSRF. Relationship between posterior putamen [¹¹C]DTBZ binding and %GSC was modified by PSRF; in those with ≥ 1 PSRF (but not in those with no PSRF), posterior putamen [¹¹C]DTBZ binding was associated with %GSC (β = 0.198, p = 0.03) independent of potential confounders. This cross-sectional study indicates that higher striatal dopaminergic neurotransmission may compensate for the effects of PSRF on gait slowing.

确定补偿老年人慢速步态的机制至关重要。多巴胺能神经传递抑制了脑血管疾病与步态的有害关联，但它是否补偿了周围系统危险因素（PSRF）对步态减慢的影响尚未得到研究。在这项社区老年人的横断面研究中，我们研究了黑质纹状体多巴胺能末端完整性与步态速度之间的关系，这些个体有或没有≥1个PSRF导致步态减慢：肥胖、关节疼痛或肌肉力量下降。主要结局是步态速度成本（%GSC）从平坦的表面过渡到不平坦的表面。参与者使用二氢四苯那嗪[11C]DTBZ正电子发射断层扫描进行多巴胺能成像。197例个体中，平均（SD）年龄74.92（4.53）岁；女性占61.93%；90.86%（白人），130例（65.99%）PSRF≥1。PSRF改变后壳核[11C]DTBZ结合与%GSC的关系；在PSRF≥1的患者中（而非无PSRF的患者），后壳核[11C]DTBZ结合与%GSC相关（β = 0.198, p = 0.03），独立于潜在的混杂因素。这项横断面研究表明，较高的纹状体多巴胺能神经传递可能补偿PSRF对步态减慢的影响。

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引用次数: 0

Effects of global Ripk2 genetic deficiency in aged mice following experimental ischemic stroke Ripk2基因缺失对实验性缺血性脑卒中老年小鼠的影响

IF 1.7 Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2025-01-01 Epub Date: 2025-03-29 DOI: 10.1016/j.nbas.2025.100135

John Aaron Howell , Jonathan Larochelle , Rachel E. Gunraj , Sofia M. Stansbury , Lei Liu , Changjun Yang , Eduardo Candelario-Jalil

Besides the loss of blood and oxygen reaching the ischemic tissue, many secondary effects of ischemic stroke can cause additional tissue damage, including inflammation, oxidative stress, and proteomic disturbances. Receptor-interacting serine/threonine kinase 2 (RIPK2) is an important mediator in the post-stroke inflammatory cascade that responds to signals and molecular patterns released by dead or dying cells in the ischemic area. We hypothesize that RIPK2 signaling worsens injury and neurological recovery post-stroke and that global deletion of Ripk2 is protective following ischemic stroke in aged mice. Aged (18–24 months) male mice were subjected to permanent middle cerebral artery occlusion (pMCAO). Vertical grid, weight grip, and open field were conducted at baseline and on days 1, 2, 3, 8, 15, and 22 post-stroke. Cognitive tests (novel object recognition and Y-maze) were performed at baseline and day 28 post-stroke. Infarct size was measured using cresyl violet staining, and reactive gliosis was measured using Iba1 and GFAP staining at day 28 post-stroke. Global deletion of Ripk2 (Ripk2^-/-) in aged mice resulted in smaller infarct volume and improved performance on vertical grid and weight grip tests compared to aged wildtype (WT) mice. Additionally, aged Ripk2^-/- mice had less Iba1 staining in the ipsilateral cortex than the aged WT control mice. This study further elucidates the role of RIPK2 signaling in the ischemic cascade and expands our knowledge of RIPK2 in stroke to aged mice. These results support the hypothesis that RIPK2 signaling worsens injury post-stroke and may be an attractive candidate for therapeutic intervention.

除了到达缺血组织的血液和氧气的损失外，缺血性中风的许多继发性影响可引起额外的组织损伤，包括炎症、氧化应激和蛋白质组紊乱。受体相互作用丝氨酸/苏氨酸激酶2 （RIPK2）是脑卒中后炎症级联反应的重要介质，对缺血区域死亡或垂死细胞释放的信号和分子模式做出反应。我们假设RIPK2信号恶化了中风后的损伤和神经恢复，RIPK2的整体缺失在老年小鼠缺血性中风后具有保护作用。老龄（18-24月龄）雄性小鼠永久性大脑中动脉闭塞（pMCAO）。在基线和中风后第1、2、3、8、15和22天进行垂直网格、抓地力和空地研究。认知测试（新物体识别和y迷宫）在基线和中风后第28天进行。脑卒中后第28天，用甲酚紫染色测定梗死面积，用Iba1和GFAP染色测定反应性胶质细胞形成。与衰老野生型（WT）小鼠相比，衰老小鼠中Ripk2 （Ripk2-/-）的整体缺失导致梗死体积变小，在垂直网格和重量抓握测试中的表现也有所改善。此外，衰老的Ripk2-/-小鼠同侧皮质的Iba1染色比衰老的WT对照小鼠少。本研究进一步阐明了RIPK2信号在缺血性级联中的作用，并扩展了我们对RIPK2在老年小鼠中风中的认识。这些结果支持了RIPK2信号恶化脑卒中后损伤的假设，可能是治疗干预的一个有吸引力的候选者。

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引用次数: 0

White matter differences between younger and older adults revealed by fixel-based analysis 基于固定颗粒的分析揭示了年轻人和老年人的白质差异

IF 1.7 Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-11-23 DOI: 10.1016/j.nbas.2024.100132

Feliberto de la Cruz , Andy Schumann , Katrin Rieger , Daniel Güllmar , Jürgen R. Reichenbach , Karl-Jürgen Bär

The process of healthy aging involves complex alterations in neural structures, with white matter (WM) changes significantly impacting cognitive and motor functions. Conventional methods such as diffusion tensor imaging provide valuable insights, but their limitations in capturing complex WM geometry advocate for more advanced approaches. In this study involving 120 healthy volunteers, we investigated whole-brain WM differences between young and old individuals using a novel technique called fixel-based analysis (FBA). This approach revealed that older adults exhibited reduced FBA-derived metrics in several WM tracts, with frontal areas particularly affected. Surprisingly, age-related differences in FBA-derived measures showed no significant correlation with risk factors such as alcohol consumption, exercise frequency, or pulse pressure but predicted cognitive performance. These findings emphasize FBA’s potential in characterizing complex WM changes and the link between cognitive abilities and WM alterations in healthy aging. Overall, this study advances our understanding of age-related neurodegeneration, highlighting the importance of comprehensive assessments that integrate advanced neuroimaging techniques, cognitive evaluation, and demographic factors to gain insights into healthy aging.

健康老龄化过程涉及神经结构的复杂变化，其中白质（WM）的变化对认知和运动功能有重大影响。扩散张量成像等传统方法能提供有价值的见解，但它们在捕捉复杂的 WM 几何结构方面存在局限性，因此需要更先进的方法。在这项涉及 120 名健康志愿者的研究中，我们使用一种名为 "基于定点的分析"（FBA）的新技术，研究了年轻人和老年人之间的全脑 WM 差异。这种方法显示，老年人在多个 WM 束中表现出 FBA 衍生指标的减少，额叶区域尤其受到影响。令人惊讶的是，FBA衍生指标中与年龄相关的差异与饮酒、运动频率或脉压等风险因素没有显著相关性，但却能预测认知表现。这些发现强调了 FBA 在描述复杂的 WM 变化方面的潜力，以及在健康老龄化过程中认知能力与 WM 变化之间的联系。总之，这项研究加深了我们对与年龄相关的神经退行性变的理解，强调了综合评估的重要性，即整合先进的神经影像技术、认知评估和人口因素，以深入了解健康老龄化。

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引用次数: 0

Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function 脑特异性牛磺酸病损害外周骨骼肌的完整性和功能

Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-02-24 DOI: 10.1016/j.nbas.2024.100110

Bryan Alava , Gabriela Hery , Silvana Sidhom , Miguel Gutierrez-Monreal , Stefan Prokop , Karyn A. Esser , Jose Abisambra

Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.

牛头蛋白病是一种神经退行性疾病，细胞内牛头蛋白的病理性聚集会导致认知障碍。此外，临床研究报告称，患有牛头蛋白病的人群肌肉无力。然而，神经元病理tau物种是否会导致肌肉无力，以及原发性tau病的骨骼肌是否能保持收缩能力，目前仍是未知数。在这里，我们利用腺相关病毒血清型8（AAV8）表达人类突变体P301L-tau，在原发性tau病小鼠模型中发现了骨骼肌异常。AAV8-P301L 小鼠表现出握力缺陷、多动和骨骼肌组织学特征异常。此外，AAV8-P301L肌纤维肌肉横截面的空间分辨基因表达也发生了改变。转录变化显示编码肌纤维蛋白的基因发生了改变，从而提出了一种虚弱表型。引人注目的是，AAV8-P301L tau雄性小鼠比目鱼肌的特异性力量减弱。我们的研究结果表明，tau病会对骨骼肌产生外周影响，从而导致tau病的虚弱。

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引用次数: 0

Longitudinal data are crucial for identifying superagers 纵向数据对确定超级用户至关重要

Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-06-08 DOI: 10.1016/j.nbas.2024.100118

Lars Nyberg

引用次数: 0

TMS-derived short afferent inhibition discriminates cognitive status in older adults without dementia TMS 衍生的短传入抑制可判别未患痴呆症的老年人的认知状态

IF 1.7 Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-07-19 DOI: 10.1016/j.nbas.2024.100123

Mark H. Sundman , Jacob M. Green , Andrew J. Fuglevand , Ying-hui Chou

Aging is a complex and diverse biological process characterized by progressive molecular, cellular, and tissue damage, resulting in a loss of physiological integrity and heightened vulnerability to pathology. This biological diversity corresponds with highly variable cognitive trajectories, which are further confounded by genetic and environmental factors that influence the resilience of the aging brain. Given this complexity, there is a need for neurophysiological indicators that not only discern physiologic and pathologic aging but also closely align with cognitive trajectories. Transcranial Magnetic Stimulation (TMS) may have utility in this regard as a non-invasive brain stimulation tool that can characterize features of cortical excitability. Particularly, as a proxy for central cholinergic function, short-afferent inhibition (SAI) dysfunction is robustly associated with cognitive deficits in the latter stages of Alzheimer’s Disease and Related Dementia (ADRD). In this study, we evaluated SAI in healthy young adults and older adults who, though absent clinical diagnoses, were algorithmically classified as cognitively normal (CN) or cognitively impaired (CI) according to the Jak/Bondi actuarial criteria. We report that SAI is preserved in the Old-CN cohort relative to the young adults, and SAI is significantly diminished in the Old-CI cohort relative to both young and CN older adults. Additionally, diminished SAI was significantly associated with impaired sustained attention and working memory. As a proxy measure for central cholinergic deficits, we discuss the potential value of SAI for discerning physiological and pathological aging.

衰老是一个复杂多样的生物过程，其特点是分子、细胞和组织逐渐受损，导致生理完整性丧失，更容易发生病变。这种生物多样性与千变万化的认知轨迹相对应，而影响衰老大脑恢复能力的遗传和环境因素又进一步加剧了这种多样性。鉴于这种复杂性，我们需要一种神经生理指标，它不仅能辨别生理和病理衰老，还能与认知轨迹紧密结合。经颅磁刺激（TMS）作为一种非侵入性的脑刺激工具，可以描述大脑皮层兴奋性的特征，因此在这方面可能具有实用价值。特别是，作为中枢胆碱能功能的代表，短感觉抑制（SAI）功能障碍与阿尔茨海默病及相关痴呆症（ADRD）后期的认知障碍密切相关。在这项研究中，我们对健康的年轻人和老年人的 SAI 进行了评估，这些人虽然没有临床诊断，但根据 Jak/Bondi 精算标准被算法分类为认知正常（CN）或认知受损（CI）。我们的报告显示，与年轻人相比，老年认知障碍组群中的SAI得到了保留，而与年轻人和认知障碍老年人相比，老年认知障碍组群中的SAI明显减弱。此外，SAI 的减弱与持续注意力和工作记忆的受损有显著关联。作为中枢胆碱能缺陷的替代测量指标，我们讨论了 SAI 在鉴别生理性和病理性衰老方面的潜在价值。

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引用次数: 0

Neural correlates of home-based intervention effects on value-based sequential decision-making in healthy older adults 家庭干预对健康老年人基于价值的顺序决策影响的神经相关性

Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-02-13 DOI: 10.1016/j.nbas.2024.100109

Kathleen Kang , Daria Antonenko , Franka Glöckner , Agnes Flöel , Shu-Chen Li

Older adults demonstrate difficulties in sequential decision-making, which is partly attributed to under-recruitment of prefrontal networks. It is, therefore, important to understand the mechanisms that may improve this ability. This study investigated the effectiveness of an 18-sessions, home-based cognitive intervention and the neural mechanisms that underpin individual differences in intervention effects. Participants were required to learn sequential choices in a 3-stage Markov decision-making task that would yield the most rewards. Participants were assigned to better or worse responders group based on their performance at the last intervention session (T18). Better responders improved significantly starting from the fifth intervention session while worse responders did not improve across all training sessions. At post-intervention, only better responders showed condition-dependent modulation of the dorsolateral prefrontal cortex (DLPFC) as measured by fNIRS, with higher DLPFC activity in the delayed condition. Despite large individual differences, our data showed that value-based sequential-decision-making and its corresponding neural mechanisms can be remediated via home-based cognitive intervention in some older adults; moreover, individual differences in recruiting prefrontal activities after the intervention are associated with variations in intervention outcomes. Intervention-related gains were also maintained at three months after post-intervention. However, future studies should investigate the potential of combining other intervention methods such as non-invasive brain stimulation with cognitive intervention for older adults who do not respond to the intervention, thus emphasizing the importance of developing individualized intervention programs for older adults.

老年人在顺序决策方面表现出困难，部分原因是前额叶网络招募不足。因此，了解提高这种能力的机制非常重要。本研究调查了一项为期 18 个疗程、基于家庭的认知干预的有效性，以及导致干预效果个体差异的神经机制。参与者需要在一个三阶段马尔可夫决策任务中学习如何做出能获得最多奖励的顺序选择。根据参与者在最后一个干预环节（T18）的表现，将他们分配到反应较好或反应较差组。从第五次干预课程开始，反应较好的学员的成绩有了明显提高，而反应较差的学员在所有培训课程中的成绩都没有提高。在干预后，根据 fNIRS 测量，只有反应较好者的背外侧前额叶皮层（DLPFC）表现出与条件相关的调节，延迟条件下的 DLPFC 活性较高。尽管个体差异很大，但我们的数据表明，基于价值的顺序决策及其相应的神经机制可以通过基于家庭的认知干预对一些老年人进行补救；此外，干预后前额叶活动的个体差异与干预结果的变化有关。干预后三个月，与干预相关的收益也得以保持。不过，未来的研究应探讨将其他干预方法（如无创脑刺激）与认知干预相结合的可能性，以帮助那些对干预没有反应的老年人，从而强调为老年人制定个性化干预方案的重要性。

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引用次数: 0

Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats 微生物驱动的代谢途径改变和老年雌性 TgF344-AD 大鼠认知能力受损

Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2024-05-31 DOI: 10.1016/j.nbas.2024.100119

Abbi R. Hernandez , Erik Parker , Maham Babar , Anisha Banerjee , Sarah Ding , Alexis Simley , Thomas W. Buford

Alzheimer’s disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

阿尔茨海默病（AD）不仅会影响认知和神经病理学，还会影响其他几个方面，包括肠道微生物组（GMB）组成和新陈代谢的改变，从而对生活质量产生负面影响，并可能导致机体损伤。研究人员对20+月龄的雌性TgF344-AD大鼠和野生型大鼠进行了认知测试，测试任务包括任务获取、物体识别记忆、焦虑样行为和空间导航等多个认知领域。此外，还进行了代谢表型、整个肠道（十二指肠、空肠、回肠、结肠和粪便）的 GMB 测序、神经病理学负担评估和标记基因功能丰度预测 (PICRUSt2)。TgF344-AD大鼠在多个领域表现出明显的认知障碍，以及区域特异性GMB菌群失调。利用典型对应分析（CCA）研究了外围因素之间的关系，发现 GMB 变化与认知和代谢因素之间存在相关性。此外，在 TgF344-AD 大鼠体内，有助于重要代谢途径的肠道微生物群落发生了显著变化。这些数据表明，菌群失调可能会通过改变正常脑功能所必需的代谢相关酶通路来影响注意力缺失症的认知结果。此外，这些变化主要是在碳水化合物消化所需的肠段而非粪便样本中观察到的。这些数据支持以肠道和微生物组健康为目标来治疗注意力缺失症。

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引用次数: 0

Aging changes the expression of adenosine receptors, insulin-like growth factor 1 (IGF1), and hypoxia-inducible factor 1α (HIF1α) in hypothalamic astrocyte cultures 衰老会改变下丘脑星形胶质细胞培养物中腺苷受体、胰岛素样生长因子 1 (IGF1) 和缺氧诱导因子 1α (HIF1α) 的表达

Q3 CLINICAL NEUROLOGY

Aging brain

Pub Date : 2024-01-01 Epub Date: 2023-12-23 DOI: 10.1016/j.nbas.2023.100104

Camila Leite Santos , Larissa Daniele Bobermin , André Quincozes-Santos

The aging process induces neurochemical alterations in different brain regions, including hypothalamus. This pivotal area of the central nervous system (CNS) is crucial for detection and integration of nutritional and hormonal signals from the periphery of the body to maintain metabolic homeostasis. Astrocytes support the CNS homeostasis, energy metabolism, and inflammatory response, as well as increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions and in gliocrine system. In this study, we aimed to investigate the age-dependent mRNA expression of adenosine receptors, the insulin-like growth factor 1 receptor (IGF1R), and the hypoxia-inducible factor 1α (HIF1α), in addition to the levels of IGF1 and HIF1α in hypothalamic astrocyte cultures derived from newborn, adult, and aged rats. Our results revealed age-dependent changes in adenosine receptors, as well as a decrease in IGF1R/IGF1 and HIF1α. Of note, adenosine receptors, IGF1, and HIF1α are affected by inflammatory, redox, and metabolic processes, which can remodel hypothalamic properties, as observed in aging brain, reinforcing the role of hypothalamic astrocytes as targets for understanding the onset and/or progression of age-related diseases.

衰老过程会诱发包括下丘脑在内的不同脑区的神经化学变化。中枢神经系统（CNS）的这一关键区域对于检测和整合来自身体外围的营养和激素信号以维持代谢平衡至关重要。星形胶质细胞支持中枢神经系统的平衡、能量代谢和炎症反应，越来越多的证据表明星形胶质细胞在协调下丘脑功能和神经胶质系统中发挥着关键作用。在这项研究中，我们旨在研究新生大鼠、成年大鼠和老龄大鼠下丘脑星形胶质细胞培养物中腺苷受体、胰岛素样生长因子1受体（IGF1R）和缺氧诱导因子1α（HIF1α）的mRNA表达以及IGF1和HIF1α的水平随年龄的变化。我们的研究结果表明，腺苷受体的变化与年龄有关，IGF1R/IGF1 和 HIF1α 的变化也与年龄有关。值得注意的是，腺苷受体、IGF1和HIF1α会受到炎症、氧化还原和新陈代谢过程的影响，这些过程会重塑下丘脑的特性，正如在衰老大脑中观察到的那样，这加强了下丘脑星形胶质细胞作为了解与年龄相关疾病的发生和/或进展的靶标的作用。

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引用次数: 0