Behavioural Brain Research最新文献_第10页

Resveratrol prevents arsenic-induced depression-like phenotypes via modulation of BDNF signaling 白藜芦醇通过调节BDNF信号传导阻止砷诱导的抑郁样表型。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-09 DOI: 10.1016/j.bbr.2025.115988

Mohaddeseh Kharazmi , Tayyebeh Khalili , Marzieh Dehghan-Shasaltaneh , Abbas Bahari , Mohaddeseh Ebrahimi-Ghiri

Growing evidence suggests that resveratrol possesses neuroprotective properties against arsenic toxicity. This study investigated whether resveratrol could ameliorate arsenic-induced depression-like behaviors in male Naval Medical Research Institute (NMRI) mice and explored potential molecular mechanisms. Mice were exposed to arsenic (50 mg/L in drinking water) for 4 weeks and treated with resveratrol (10 or 20 mg/kg). Behavioral assessments included the hole-board test (HBT) for exploratory behavior, and the sucrose splash test (SST), tail suspension test (TST), and forced swim test (FST) for depression-like behaviors. The mRNA levels of Bdnf, Creb1, and Dvl1 in the brain were analyzed by qRT-PCR. Arsenic exposure induced significant depression-like behaviors, characterized by decreased grooming in SST and increased immobility in TST and FST. Resveratrol treatment prevented these behavioral alterations and exhibited intrinsic antidepressant effects in naïve mice, with dose-dependent reductions in immobility time (FST) and increased grooming (SST). Notably, resveratrol (20 mg/kg) enhanced rearing frequency in naïve mice and decreased it in the arsenic-treated mice. At the molecular level, arsenic downregulated Bdnf expression, while resveratrol restored its levels. In contrast, no significant changes in Creb1 and Dvl1 expression were observed. These findings indicate that resveratrol mitigates arsenic-induced depression-like behaviors primarily through the modulation of Bdnf-dependent pathways, independent of Creb1 and Dvl1. These results position resveratrol as a potential antidepressant and underscore its therapeutic promise for mood disorders associated with environmental toxicant exposure.

越来越多的证据表明，白藜芦醇具有抗砷毒性的神经保护特性。本研究旨在探讨白藜芦醇是否能改善美国海军医学研究所（Naval Medical Research Institute， NMRI）雄性小鼠砷诱导的抑郁样行为，并探讨可能的分子机制。小鼠暴露于砷（饮用水中50mg/L） 4周，并用白藜芦醇（10或20mg/kg）处理。行为评估包括探索性行为的孔板测试（HBT），以及抑郁样行为的蔗糖飞溅测试（SST）、悬尾测试（TST）和强迫游泳测试（FST）。采用qRT-PCR分析脑内Bdnf、Creb1、Dvl1 mRNA表达水平。砷暴露诱导了显著的抑郁样行为，其特征是SST的修饰减少，TST和FST的不动增加。在naïve小鼠中，白藜芦醇治疗阻止了这些行为改变，并表现出内在的抗抑郁作用，其剂量依赖性地减少了静止时间（FST）和增加了梳洗（SST）。值得注意的是，白藜芦醇（20mg/kg）提高了naïve小鼠的饲养频率，降低了砷处理小鼠的饲养频率。在分子水平上，砷降低了Bdnf的表达，而白藜芦醇则恢复了Bdnf的表达。相比之下，Creb1和Dvl1的表达没有明显变化。这些发现表明，白藜芦醇减轻砷诱导的抑郁样行为主要是通过调节bdnf依赖途径，独立于Creb1和Dvl1。这些结果将白藜芦醇定位为一种潜在的抗抑郁药，并强调了其治疗与环境毒物暴露相关的情绪障碍的前景。

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引用次数: 0

Retraction notice to “Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced memory impairment in rat” [Behav. Brain Res. 240 (2013) 76–86] “抑制糖皮质激素受体可改善低氧缺氧引起的大鼠记忆障碍”的撤回通知[行为]。脑科学进展，2013(4):376 - 386。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-09 DOI: 10.1016/j.bbr.2025.115980

Iswar Baitharu , Satya Narayan Deep , Vishal Jain , Dipti Prasad , G. Ilavazhagan

引用次数: 0

Time-dependent characterisation of sex differences in the chronic constriction injury (CCI) model of neuropathic pain 神经性疼痛慢性收缩损伤（CCI）模型中性别差异的时间依赖性特征。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-09 DOI: 10.1016/j.bbr.2025.115990

Joana Gonçalves , Diana Fonseca-Rodrigues , Inês Martins Laranjeira , Armando Almeida , Filipa Pinto-Ribeiro

Chronic neuropathic pain affects 7–10 % of the population and is often accompanied by emotional impairments, greatly reducing the quality of life of patients. Recently, we showed that in the chronic constriction injury (CCI) model of experimental neuropathic pain, female (but not male) rats showed a delayed but progressive development of mechanical and cold allodynia, which did not improve over time. In this work, we characterised the CCI-induced nociceptive and emotional impairments at earlier (2 weeks) and later (8 weeks) time points in both male and female rats. Both neuropathic males and females developed mechanical allodynia from week 1 onwards; however, males were shown to recover earlier at week 3, corroborated by sciatic nerve histopathology. Importantly, both males and females displayed cold allodynia throughout the experimental period (8 weeks). Regarding emotional impairments, males showed a more anxious and depressive phenotype than females, independently of CCI. Electrophysiological recordings suggest time-dependent changes in descending inhibition from the rostral ventromedial medulla (RVM) in response to CCI-induced neuropathic pain. Altogether, our results show the existence of sex-specific differences in the development and maintenance of CCI-induced nociceptive and emotional impairments, highlighting the need to include female subjects in the study of neuropathic pain mechanisms and treatments.

慢性神经性疼痛影响7-10%的人口，通常伴有情绪障碍，大大降低了患者的生活质量。最近，我们发现在实验性神经性疼痛的慢性收缩损伤（CCI）模型中，雌性（而不是雄性）大鼠表现出机械和冷异常性疼痛的延迟但进行性发展，并没有随着时间的推移而改善。在这项工作中，我们在雄性和雌性大鼠的较早（2周）和较晚（8周）时间点描述了cci诱导的伤害性和情绪损伤。从第1周开始，神经性男性和女性都出现了机械性异常性疼痛；然而，男性在第3周恢复得更早，坐骨神经组织病理学证实了这一点。重要的是，在整个实验期间（8周），雄性和雌性都表现出冷异常性痛。在情绪障碍方面，男性比女性表现出更多的焦虑和抑郁表型，与CCI无关。电生理记录表明，在cci诱导的神经性疼痛反应中，从吻侧腹内侧延髓（RVM）下降抑制的时间依赖性变化。总之，我们的研究结果表明，在cci诱导的伤害性和情绪损伤的发展和维持中存在性别特异性差异，突出了在神经性疼痛机制和治疗研究中纳入女性受试者的必要性。

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引用次数: 0

Transmuscular vocal fold injury reduces frequency complexity of rat ultrasonic vocalizations 经肌肉声带损伤可降低大鼠超声发声频率的复杂性。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-08 DOI: 10.1016/j.bbr.2025.115989

Marilla Gould , Ryosuke Nakamura , Wenqing Yang , Ryan C. Branski , Aaron M. Johnson

Rapid and precise activation of the laryngeal musculature, particularly the thyroarytenoid (TA), is required for the production of rat ultrasonic vocalizations (USVs). Although the role of the TA in USV production has been established through denervation and excised larynx studies, how TA muscle dysfunction affects USV acoustics remains unknown. This study examined how iatrogenic, transmuscular vocal fold injury influences USV production by comparing acoustic parameters between rats receiving bilateral transmuscular vocal fold injury (including the TA muscle) versus sham surgery. Twenty adult male rats were randomly assigned to injury or sham groups and assessed at 30 or 60 days post-surgery. USVs were recorded at each timepoint (pre- and post-surgery) and analyzed for changes in principal frequency, frequency complexity (standard deviation and sinuosity), power (intensity of the USV), tonality, and duration. Injury significantly decreased USV frequency complexity and reduced the likelihood of producing frequency-modulated vocalizations in both post-surgical time groups. These findings demonstrate that while TA muscle integrity is crucial for frequency modulation, it is not necessary for basic USV production, offering new insights into the biomechanical role of the TA muscle in rat vocalization and laying the groundwork for investigating therapeutic interventions targeting laryngeal muscle function.

快速和精确地激活喉部肌肉组织，特别是类甲状腺肌（TA），是产生大鼠超声发声（usv）所必需的。虽然通过去神经支配和切除喉的研究已经确定了TA在USV产生中的作用，但TA肌肉功能障碍如何影响USV声学仍然未知。本研究通过比较双侧经肌性声带损伤（包括TA肌）和假手术大鼠的声学参数，研究了医源性经肌性声带损伤对USV产生的影响。将20只成年雄性大鼠随机分为损伤组和假手术组，分别于术后30天和60天进行评估。在每个时间点记录USV，并分析主频率、频率复杂度（标准差和弯曲度）、功率（USV强度）、音调和持续时间的变化。损伤显著降低了USV频率的复杂性，并减少了术后两个时间点产生调频发声的可能性。这些发现表明，虽然TA肌的完整性对于频率调制至关重要，但对于基本的USV产生并非必需，这为TA肌在大鼠发声中的生物力学作用提供了新的见解，并为研究针对喉肌功能的治疗干预奠定了基础。

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引用次数: 0

Effects of intranasal oxytocin administration on histophysiology of the hippocampus in maternally separated adolescent male rats 鼻内注射催产素对母分离雄性大鼠海马组织生理学的影响。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-08 DOI: 10.1016/j.bbr.2025.115983

Parisa Salehi Najafabadi , Ali Shamsara , Vida Mirzaie , Vahid Sheibani , Mahdiyeh Ahmadi , Sara Joushi , Mohsen Basiri

Astrocytes are one of the glial cells of the nervous system. These cells reach their maximum number in the first two weeks after birth. Therefore, during this period they are sensitive to adverse conditions, including separation from the mother. One of the factors is the stress-modulating hormone oxytocin (OT). Adolescent male Wistar rats were used in this study. Rat pups were subjected to the MS protocol for 180 min per day from postnatal day 1–21 (postnatal day (PND)). Then, from PND 22–34, OT was administered intranasally (2 μg/μl, for 7 days). Behavioral assessments were performed on PND 35–37, we prespecified glial fibrillary acidic protein (GFAP)+ astrocyte density and morphology as the primary outcome, given astrocytes’ active roles in synaptic plasticity, stress regulation, and oxytocin signaling; the neuron degeneration ratio and p38/p-p38 expression were treated as secondary outcomes. MS did not alter locomotion; it increased anxiety-like behavior in the Zero Maze Test (ZMT) (but not in the Open Field Test (OFT)) and elevated olfactory thresholds. MS also increased the degenerated/healthy neuron ratio and p38/p-p38 protein levels, and reduced GFAP+ astrocyte density and process size in hippocampal CA1; OT partly reversed these glial/inflammatory changes without affecting the neuron degeneration ratio. These findings suggest that OT could serve as a therapeutic agent to improve some of the adverse behavioral and histological effects of MS in modern societies.

星形胶质细胞是神经系统的一种胶质细胞。这些细胞在出生后的前两周达到最大数量。因此，在此期间，他们对不利条件很敏感，包括与母亲分离。其中一个因素是压力调节激素催产素（OT）。本研究采用青春期雄性Wistar大鼠。从大鼠出生后第1天至第21天（PND），每天进行180分钟的MS治疗。然后，从PND 22至34，经鼻给药OT （2μg/μl, 7 d）。考虑到星形胶质细胞在突触可塑性、应激调节和催产素信号传导方面的积极作用，我们预先指定了胶质纤维酸性蛋白(GFAP)+星形胶质细胞密度和形态作为主要结果；神经元变性率和p38/p-p38表达作为次要结局。MS不改变运动；它在零迷宫测试（ZMT）中增加了焦虑样行为（但在开放场地测试（OFT）中没有），并提高了嗅觉阈值。MS还增加了退化/健康神经元比例和p38/p-p38蛋白水平，降低了海马CA1中GFAP+星形胶质细胞密度和过程大小；OT部分逆转了这些胶质/炎症变化，而不影响神经元变性率。这些发现表明，在现代社会中，OT可以作为一种治疗药物来改善MS的一些不良行为和组织学影响。

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引用次数: 0

Aberrant prefrontal network patterns in post-stroke prolonged disorders of consciousness: Evidence from resting-state fNIRS 脑卒中后延长意识障碍的异常前额叶网络模式：来自静息状态近红外光谱的证据。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-08 DOI: 10.1016/j.bbr.2025.115987

Yu Gong , Ningqing Xie , Ying Liu , Junbin Lin , Jun Zheng , Chizi Hao , Hailong Huang , Ting Jiang , Lu Xia , Kai Fu , Xin Zhang , Weijing Liao

Stroke represents a leading cause of non-traumatic prolonged disorders of consciousness (pDoC). Given the prefrontal cortex's critical role in consciousness, this study aimed to explore the abnormalities in the prefrontal network in post-stroke pDoC patients. Using resting-state functional near-infrared spectroscopy (fNIRS), we acquired data from 21 post-stroke pDoC patients and 19 age- and gender-matched healthy controls (HC). Based on the Coma Recovery Scale-Revised, patients were classified into 12 with minimally conscious state (MCS) and 9 with unresponsive wakefulness syndrome (UWS). We analyzed and compared functional connectivity and topological properties of the prefrontal network across groups. Compared to HCs, the pDoC group exhibited extensively weakened functional connectivity and disrupted network topology, as evidenced by a lower clustering coefficient (Cp), reduced local efficiency (Eloc), global efficiency (Eg) and a longer characteristic path length (Lp). Reductions in key nodal metrics which including nodal clustering coefficient (NCp), nodal efficiency (Ne), and degree centrality (DC) were also observed across several prefrontal regions. In the direct comparison between patient subgroups, the MCS group demonstrated significantly stronger functional connectivity within the right premotor and supplementary motor cortex (PreM & SMA_R) than the UWS group, but conversely, showed weaker connectivity within the left frontopolar area (FPA_L). Consequently, assessing prefrontal network integrity with portable fNIRS holds promise for identifying potential biomarkers to diagnose and monitor post-stroke prolonged disorders of consciousness.

中风是非创伤性意识障碍（pDoC）的主要原因。鉴于前额叶皮层在意识中起着至关重要的作用，本研究旨在探讨脑卒中后pDoC患者前额叶网络的异常。使用静息状态功能近红外光谱（fNIRS），我们获得了21例卒中后pDoC患者和19例年龄和性别匹配的健康对照组（HC）的数据。根据修订后的昏迷恢复量表，将患者分为12例最低意识状态（MCS）和9例无反应性清醒综合征（UWS）。我们分析和比较了各组前额叶网络的功能连通性和拓扑特性。与hc相比，pDoC组的功能连通性被广泛削弱，网络拓扑结构被破坏，表现为较低的聚类系数（Cp）、较低的局部效率（Eloc）和全局效率（Eg）以及较长的特征路径长度（Lp）。包括节点聚类系数（NCp）、节点效率（Ne）和度中心性（DC）在内的关键节点指标在几个前额叶区域也有所减少。在患者亚组之间的直接比较中，MCS组在右侧运动前和辅助运动皮层（PreM & SMA_R）内的功能连通性明显强于UWS组，而相反，在左侧额极区（FPA_L）内的功能连通性较弱。因此，使用便携式近红外光谱（fNIRS）评估前额叶网络完整性有望识别潜在的生物标志物，以诊断和监测中风后延长的意识障碍。

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引用次数: 0

Age-dependent effects of intranasal oxytocin administration were revealed by resting brain entropy (BEN) 静息脑熵（BEN）揭示了鼻内催产素的年龄依赖性效应。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-06 DOI: 10.1016/j.bbr.2025.115985

Donghui Song , Ze Wang

Oxytocin (OT), a neuropeptide known for its role in social behavior, has unclear neural mechanisms when administered intranasally, especially across different ages. Brain entropy (BEN), a metric of neural irregularity, shows promise for revealing OT’s neurophysiological effects. This study examined whether BEN could detect neural changes induced by intranasal OT and how these effects are modulated by age. In a randomized, double-blind, placebo-controlled trial, young adults (YA) and older adults (OA) were assigned to receive intranasal OT or placebo (PL). Using fMRI-based BEN mapping, we identified a significant age-dependent effect in the left temporoparietal junction (TPJ), where OT increased BEN in YA but decreased it in OA. Further analyses showed OT also elevated the fractional amplitude of low-frequency fluctuations (fALFF) in the same region, particularly in YA. Additionally, OT enhanced functional connectivity within the left TPJ and between the left and right TPJ in both age groups. These results establish BEN as a sensitive biomarker capable of capturing age-specific OT effects, providing information beyond traditional measures of oscillatory power and temporal synchronization. The findings suggest that the timing of post-administration brain state changes under OT may vary with age, potentially due to differences in OT receptor density.

催产素（OT）是一种以其在社会行为中的作用而闻名的神经肽，当鼻内给药时，特别是在不同年龄的人，其神经机制尚不清楚。脑熵（BEN）是一种衡量神经不规则性的指标，有望揭示OT的神经生理效应。本研究考察了BEN是否能检测鼻内OT引起的神经变化，以及这些影响如何随年龄而调节。在一项随机、双盲、安慰剂对照试验中，年轻人（YA）和老年人（OA）被分配接受鼻内OT或安慰剂（PL）。使用基于fmri的BEN图谱，我们在左颞顶交界处（TPJ）发现了显著的年龄依赖性效应，其中OT增加了YA的BEN，但降低了OA的BEN。进一步的分析表明，OT还提高了同一区域的低频波动（fALFF）的分数幅度，特别是在YA中。此外，在两个年龄组中，OT增强了左TPJ内部以及左右TPJ之间的功能连通性。这些结果表明BEN是一种敏感的生物标志物，能够捕捉年龄特异性OT效应，提供超越传统振荡功率和时间同步测量的信息。研究结果表明，OT治疗后大脑状态变化的时间可能随年龄而变化，可能是由于OT受体密度的差异。

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引用次数: 0

PVN AVP neurons projecting to MeA modulate social recognition and anxiety-like behavior in female mice 雌性小鼠PVN AVP神经元向MeA的投射调节社会识别和焦虑样行为。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-06 DOI: 10.1016/j.bbr.2025.115984

Weizheng Zhang , Caihong Huang , Jing Liu , Lu Li , Yuting Bai , Yahan Sun , Lizi Zhang , Lu Ren , Kaizhe Huang , Shaoxiong Yan , Zhixiong He , Fadao Tai

Arginine vasopressin (AVP) is well established in regulating social cognition and emotional responses in males. However, its roles in these processes in females and the underlying circuit mechanisms, remain poorly understood. In this study, female mice spent significantly more time sniffing the anogenital region of unfamiliar conspecifics compared to familiar individuals. Fiber photometry recordings revealed that the calcium activity in paraventricular nucleus of the hypothalamus (PVN) AVP neurons was elevated when sniffing unfamiliar mice relative to familiar ones. No significant differences were observed during non-social exploratory behaviors such as bedding sniffing or self-grooming, indicating a specific involvement of these neurons in social investigation. Retrograde tracing using cholera toxin B (CTB) confirmed direct projections from AVP neurons in the PVN to the medial amygdala (MeA). Chemogenetic inhibition of the PVN-MeA AVPergic pathway impaired social recognition and reduced anxiety-like behaviors. Furthermore, bilateral microinjection of the V1a receptor (V1aR) antagonist into the MeA decreased both anxiety-like behaviors and social investigation toward unfamiliar mice. These findings demonstrate that the AVPergic projection from the PVN to the MeA modulates social cognition and emotional state in female mice, providing a circuit mechanism for social and affective dysregulation and offering potential targets for the treatment of related neuropsychiatric disorders.

精氨酸抗利尿激素（AVP）在调节男性社会认知和情绪反应方面已经得到了很好的证实。然而，它在女性的这些过程中的作用和潜在的电路机制，仍然知之甚少。在这项研究中，与熟悉的个体相比，雌性小鼠花更多的时间嗅闻不熟悉的同种个体的肛门生殖器区域。纤维光度测定结果显示，下丘脑室旁核（PVN） AVP神经元的钙活性在闻陌生小鼠时明显高于闻熟悉小鼠。在非社会探索行为（如闻被褥或自我梳理）中没有观察到显著差异，表明这些神经元在社会调查中有特定的参与。使用霍乱毒素B （CTB）逆行追踪证实了PVN的AVP神经元直接投射到内侧杏仁核（MeA）。PVN-MeA avperic通路的化学发生抑制损害了社会认知并减少了焦虑样行为。此外，双侧微注射V1a受体（V1aR）拮抗剂到MeA中可以减少对陌生小鼠的焦虑样行为和社会调查。这些发现表明，从PVN到MeA的AVPergic投射调节了雌性小鼠的社会认知和情绪状态，为社会和情感失调提供了一种回路机制，并为相关神经精神疾病的治疗提供了潜在的靶点。

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引用次数: 0

A review of treatment methods for movement disorders 运动障碍的治疗方法综述

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-04 DOI: 10.1016/j.bbr.2025.115979

Mahdi Khezri , Shakiba Afsar

Movement is a critical component of human functionality, influencing daily activities and overall quality of life. For this reason, precise and complete execution of the movements is extremely important. However, traumatic and non-traumatic pathologies can impair neuromuscular and musculoskeletal systems, leading to motor dysfunction. Accurate etiological diagnosis and evidence-based therapeutic strategies are crucial in managing movement disorders, whether through restorative treatment or symptomatic relief. This study investigates the multifactorial pathogenesis of movement disorders and provides a comprehensive review of current therapeutic approaches, including rehabilitation strategies, pharmacological management, surgical interventions, and emerging treatment modalities. The selection of accurate, patient-specific therapeutic interventions enables clinicians to optimize motor function and minimize disability in patients with movement disorders.

运动是人体功能的重要组成部分，影响日常活动和整体生活质量。因此，精确和完整的动作执行是极其重要的。然而，创伤性和非创伤性病理可损害神经肌肉和肌肉骨骼系统，导致运动功能障碍。无论是通过恢复性治疗还是缓解症状，准确的病因诊断和循证治疗策略对于管理运动障碍至关重要。本研究探讨了运动障碍的多因素发病机制，并对目前的治疗方法进行了全面的综述，包括康复策略、药物管理、手术干预和新兴的治疗方式。选择准确的、患者特异性的治疗干预措施使临床医生能够优化运动功能，并最大限度地减少运动障碍患者的残疾。

引用次数: 0

Advanced age and lipopolysaccharide influence behavioral and neurodegenerative features in LRRK2 G2019S knock-in mice 高龄和脂多糖影响LRRK2 G2019S敲入小鼠的行为和神经退行性特征。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2025-12-03 DOI: 10.1016/j.bbr.2025.115970

Anuroopa Dinesh, Teresa Fortin, Hongyu Sun, Shawn Hayley

Parkinson’s disease (PD) is a progressive neurodegenerative disease thought to arise from the collective impact of advancing age, genetic vulnerabilities and possibly exposure to environmental toxicants. The LRRK2 point mutation, G2019S, is the most common genetic link with PD and has been reported to have age-dependent effects in rodents, as well as being linked to neuroinflammatory processes. Accordingly, the objective of the current study was to elucidate the interactive effects of advanced age and activation of the immune system using the bacterial endotoxin, lipopolysaccharide (LPS), in G2019S knockin mice and their wild type littermates. Adult young (3–4 months) and aged (9–12 months) mice were administered five intraperitoneal injections of 250 ug/kg of LPS (or saline) every alternate day. Significant interactions between age, genotype and injection were evident across several behavioral outcomes. In fact, the aged G2019S mice were more vulnerable to the LPS injections in terms of the sickness response, deficits in nest building behaviors, weight loss, along with protracted reductions in home cage motor activity. These mice also exhibited alterations of SNc inflammatory microglia proteins (WAVE2 and CXCR1) and had the greatest loss of substantia nigra dopamine neurons, which is consistent with a PD-like phenotype. Taken together, our data suggest that the LRRK2 G2019S mutation might be a general regulator of aging and inflammatory processes that are important for neurodegeneration, together with motor and non-motor symptoms.

帕金森病（PD）是一种进行性神经退行性疾病，被认为是由年龄增长、遗传脆弱性和可能暴露于环境毒物的共同影响引起的。LRRK2点突变G2019S是与PD最常见的遗传联系，据报道，在啮齿动物中具有年龄依赖性影响，并与神经炎症过程有关。因此，本研究的目的是阐明高龄和利用细菌内毒素脂多糖（LPS）激活免疫系统对G2019S敲入小鼠及其野生型幼崽的相互作用。将成年幼龄（3-4个月）和成年（9-12个月）小鼠腹腔注射LPS（或生理盐水）250mg/kg，每隔一天5次。在几个行为结果中，年龄、基因型和注射之间的显著相互作用是显而易见的。事实上，年老的G2019S小鼠在疾病反应、筑巢行为缺陷、体重减轻以及家庭笼子运动活动的长期减少方面更容易受到LPS注射的影响。这些小鼠还表现出SNc炎性小胶质细胞蛋白（WAVE2和CXCR1）的改变，并且黑质多巴胺神经元的损失最大，这与pd样表型一致。综上所述，我们的数据表明，LRRK2 G2019S突变可能是衰老和炎症过程的一般调节剂，这些过程对神经退行性变以及运动和非运动症状都很重要。

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引用次数: 0