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Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway 姜黄素通过抑制炎症反应、氧化应激和激活AMPK通路来缓解阿尔茨海默病。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-19 DOI: 10.1016/j.jchemneu.2023.102363
Sen Shao , Xiaojun Ye , Wenwen Su , Yanbo Wang

Background

Alzheimer’s disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD.

Materials and Methods

Firstly, we established AD mice by injecting amyloid-β1–42 (Aβ1–42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aβ1–42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot.

Results

Cur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aβ1–42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1β and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation.

Conclusion

Cur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.

背景:阿尔茨海默病(AD)是一种常见的退行性脑疾病,治疗方案有限。姜黄素在许多疾病中具有神经保护作用。我们旨在探讨Cur在AD中的作用和机制。材料和方法:首先,通过在海马内注射淀粉样蛋白-β1-42 (a -β1-42)溶液建立AD小鼠。然后给AD小鼠注射150mg/kg/d的Cur,连续10 d。采用Morris水迷宫实验,通过隐蔽平台训练和探针试验来评价小鼠的认知功能。为了评估小鼠的空间记忆,在y迷宫测试中,记录小鼠的自发交替行为、穿越新臂的次数和在新臂上花费的时间。采用苏木精和伊红(H&E)染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNAL)法评估脑组织病理损伤和凋亡情况。尼氏染色观察损伤神经元数量。免疫组化染色检测a - β1-42沉积。采用酶联免疫吸附法(ELISA)检测大鼠血清和海马组织中肿瘤坏死因子-α (TNF-a)、白细胞介素-6 (IL-6)和白细胞介素-1β (IL-1β)水平,脑组织中超氧化物歧化酶(SOD)和丙二醛(MDA)含量。Western blot检测b细胞淋巴瘤-2 (Bcl-2)、Bcl-2相关X蛋白(Bax)、RelA (p65)蛋白表达和腺苷5′-单磷酸活化蛋白激酶(AMPK)磷酸化水平。结果:枸杞不仅能改善AD小鼠的认知功能和空间记忆,还能减轻AD小鼠脑组织的病理损伤和细胞凋亡。同时,经Cur处理后,AD小鼠损伤神经元数量减少,a - β1-42水平显著降低。此外,用Cur处理的AD小鼠表现出较低的TNF-a、IL-6、IL-1β和MDA水平和较高的SOD含量。此外,Cur还下调p65的表达,上调AMPK的磷酸化。结论:莪术可能通过抑制炎症反应、氧化应激和激活AMPK通路改善AD,提示莪术可能是治疗AD的潜在药物。
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引用次数: 0
Spatiotemporal expression patterns of ZBP1 in the brain of mouse experimental stroke model 小鼠实验性脑卒中模型中ZBP1的时空表达规律
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-10 DOI: 10.1016/j.jchemneu.2023.102362
Tohru Mutoh , Hiroshi Kikuchi , Tatsuya Jitsuishi , Keiko Kitajo , Atsushi Yamaguchi

Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor, functioning as a critical mediator of inflammation and cell death pathways. Since neuroinflammation could occur in response to damage-associated molecular patterns (DAMPs), ZBP1 might be involved in neuroinflammation after stroke. However, the spatiotemporal expression profile of ZBP1 in the post-stroke brain remains to be elucidated. The aim of this study is to demonstrate the spatiotemporal expression patterns of ZBP1 in the post-stroke brain using a mouse photothrombotic stroke model. Real-time PCR assays showed that ZBP1 is induced on days 3–14 post stroke. ZBP1 immunoreactivity was observed in Iba1-positive microglia/macrophages in peri-infarct regions by immunohistochemistry. ZBP1-positive cells were spread in layers surrounding the infarct core by 7–14 days post stroke. Interestingly, ZBP1 immunoreactivity was also detected in CD206-positive border-associated macrophages (BAMs) in the meninges. Furthermore, ZBP1-expressing cells were positive for antibodies against inflammatory mediators such as Toll-like receptor 4 (TLR4), Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF), and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Morphological analysis with confocal microscopy showed that the co-localization signals of ZBP1 and its adaptor, TRIF, are increased by glucose oxidase (GOx) treatment, which has been reported to induce mitochondrial DNA (mtDNA) release. These results suggest that ZBP1 is induced in peri-infarct microglia/macrophages and may be involved in DAMPs-mediated neuroinflammation involving mtDNA in the post-infarct brain.

Z-DNA结合蛋白1 (ZBP1)是一种细胞质核酸传感器,是炎症和细胞死亡途径的关键介质。由于神经炎症可能是对损伤相关分子模式(DAMPs)的反应,ZBP1可能参与中风后的神经炎症。然而,ZBP1在脑卒中后的时空表达谱仍有待阐明。本研究的目的是通过小鼠光血栓性中风模型来证明ZBP1在中风后大脑中的时空表达模式。实时荧光定量PCR检测显示ZBP1在脑卒中后3-14天被诱导。免疫组化观察梗死周围iba1阳性小胶质细胞/巨噬细胞ZBP1免疫反应性。脑卒中后7 ~ 14天,zbp1阳性细胞在梗死核心周围呈层状分布。有趣的是,在脑膜中cd206阳性的边界相关巨噬细胞(bam)中也检测到ZBP1免疫反应性。此外,表达zbp1的细胞对炎症介质如Toll样受体4 (TLR4)、Toll/IL-1R结构域受体诱导IFN-β (TRIF)和受体相互作用丝氨酸/苏氨酸蛋白激酶1 (RIPK1)的抗体呈阳性。共聚焦显微镜形态学分析显示,葡萄糖氧化酶(GOx)处理增加了ZBP1及其接头TRIF的共定位信号,并诱导线粒体DNA (mtDNA)释放。这些结果表明ZBP1在梗死周围小胶质细胞/巨噬细胞中被诱导,并可能参与梗死后脑中damps介导的涉及mtDNA的神经炎症。
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引用次数: 0
Synaptamide modulates glial and neurotransmitter activity in the spinal cord during neuropathic pain 突触酰胺在神经性疼痛过程中调节脊髓中的神经胶质和神经递质活性。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-05 DOI: 10.1016/j.jchemneu.2023.102361
Anna Starinets, Arina Ponomarenko, Anna Tyrtyshnaia, Igor Manzhulo

N-docosahexaenoylethanolamine, or synaptamide, is an endogenous metabolite of docosahexaenoic acid that is known for synaptogenic and neurogenic effects. In our previous studies we have shown that synaptamide attenuates neuropathic pain, facilitates remyelination, and reduces neuroinflammation after the chronic constriction injury (CCI) of the sciatic nerve in rats. In the current study, we show that daily synaptamide administration (4 mg/kg/day) within 14 days post-surgery: (1) decreases micro- and astroglia activity in the dorsal and ventral horns of the lumbar spinal cord; (2) modulates pro-inflammatory (IL1β, IL6) and anti-inflammatory (IL4, IL10) cytokine level in the serum and spinal cord; (3) leads to a rise in synaptamide and anandamide concentration in the spinal cord; (4) enhances IL10, CD206 and N-acylethanolamine-hydrolyzing acid amidase synthesis in macrophage cell culture following LPS-induced inflammation. Thus, the ability of synaptamide to modulate glial and cytokine activity indicates its potential for implementation in the treatment peripheral nerve injury.

N-二十二碳六烯酸乙醇胺,或称突触酰胺,是二十二碳六油酸的内源性代谢产物,具有突触发生和神经发生作用。在我们之前的研究中,我们已经表明,突触酰胺可以减轻大鼠坐骨神经慢性收缩损伤(CCI)后的神经性疼痛,促进髓鞘再生,并减少神经炎症。在目前的研究中,我们发现在手术后14天内每天给予突触酰胺(4mg/kg/天):(1)降低腰椎背角和腹角的微胶质细胞和星形胶质细胞活性;(2) 调节血清和脊髓中的促炎(IL1β,IL6)和抗炎(IL4,IL10)细胞因子水平;(3) 导致脊髓中突触酰胺和阿那达明浓度升高;(4) 增强LPS诱导的炎症后巨噬细胞培养中IL10、CD206和N-酰基乙酰胺水解酸酰胺酶的合成。因此,突触酰胺调节神经胶质和细胞因子活性的能力表明其在治疗周围神经损伤中的应用潜力。
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引用次数: 0
Effect of royal jelly on acrylamide-induced neurotoxicity in rats 蜂王浆对丙烯酰胺致大鼠神经毒性的影响。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-02 DOI: 10.1016/j.jchemneu.2023.102358
Doaa S. Ibrahim , Eman M.S. Shahen

Royal Jelly (RJ) is a natural product made by nurse bees known for its multiple therapeutic properties. The research aims to discover the ability of RJ to improve the hematological alterations and neurotoxicity caused by acrylamide (AA). The study rats were separated equally into four groups (6 in each group), the control group, the AA (38.27 mg/kg bw) group, the RJ (150 mg/kg bw) + AA group, and the RJ (300 mg/kg bw) + AA group. Blood and brain samples were collected after 10 days to evaluate haematological and biochemical parameters and to examine histopathological and immunohistochemistry. The administration of AA increased the level of malondialdehyde (MDA), decreases levels of haematological parameters, superoxide dismutase (SOD), reduced glutathione (GSH), brain-derived neurotrophic factor (BDNF), neurotransmitters (serotonin, dopamine, and acetylcholine), and cleaved caspase-3, as well as increase the damage to the brain tissues. Meanwhile, RJ improved levels of haematological parameters, oxidative stress parameters (MDA, SOD, and GSH), BDNF, neurotransmitters, cleaved caspase-3, and brain tissue damage induced by AA. The study demonstrated the protective impact of RJ against the haematological alterations and neurotoxicity caused by AA.

蜂王浆(RJ)是一种由护理蜂制成的天然产品,以其多种治疗特性而闻名。本研究旨在发现RJ改善丙烯酰胺(AA)引起的血液学改变和神经毒性的能力。研究大鼠平均分为四组(每组6只)、对照组、AA(38.27 mg/kg体重)组、RJ(150 mg/kg体重)+AA组和RJ(300 mg/kg体重)+AA组。10天后采集血液和大脑样本,以评估血液学和生化参数,并检查组织病理学和免疫组织化学。AA的给药增加了丙二醛(MDA)的水平,降低了血液学参数、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、脑源性神经营养因子(BDNF)、神经递质(血清素、多巴胺和乙酰胆碱)和裂解的胱天蛋白酶-3的水平,并增加了对脑组织的损伤。同时,RJ改善了AA诱导的血液学参数、氧化应激参数(MDA、SOD和GSH)、BDNF、神经递质、裂解的胱天蛋白酶-3和脑组织损伤的水平。研究表明,RJ对AA引起的血液学改变和神经毒性具有保护作用。
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引用次数: 0
Lymphatic vessels accompanying dorsal and basal dural sinuses in the human brain 伴人脑脊膜窦背窦和基底窦的淋巴管
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-28 DOI: 10.1016/j.jchemneu.2023.102357
Safiye Çavdar , Büşra Köse , Damlasu Altınöz , Gizem Söyler , Ahmet Cingöz , İlke Ali Gürses , Mazhar Özkan , Hızır Aslıyüksek , Halit Çakır

Recent investigations showed the presence of meningeal lymphatic vessels (mLVs) along the superior sagittal and transverse dural sinuses which drain both fluid and immune cells from the cerebrospinal fluid (CSF) to the deep cervical lymph nodes. This study uses immunohistochemistry (IHC) and the Western Blot technique to show the presence of mLV accompanying the dorsal (superior sagittal, inferior sagittal, transverse, sigmoid, and straight) and basal (cavernous, sphenoparietal, superior, and inferior petrosal) dural sinuses in the human brain. Samples for IHC were obtained from dorsal and basal meningeal dural sinuses of 3 human cadavers and 3 autopsies. Routine histological techniques were carried out for the specimens. Podoplanin (PDPN, lymphatic vessel endothelial cell marker) and CD31 (vascular endothelial cell marker) IHC staining were applied to the 5 µm thick paraffin sections. Furthermore, PDPN and CD31 protein expressions were evaluated using Western Blot to the tissue samples from the same regions of 4 autopsies. Two consecutive sections from each sinus were PDPN, and CD31 was stained to differentiate blood vessels (BV) from mLV. The IHC staining showed the presence of mLVs accompanying both dorsal and basal dural sinuses. The mLVs accompanying the dorsal dural sinuses had a larger dimensions range compared to the basal dural sinuses. However, the number of mLVs along the basal dural sinuses was more than the mLVs along the dorsal ones. Further, fluid channels were closely localized to the mLV, with varying diameters and densities. Western Blotting technique showed the presence of PDPN expression in both dorsal and basal dural sinus samples. The knowledge of the presence of mLV along both dorsal and basal dural sinuses in humans can increase the understanding of how mLV contributes to the brain lymphatic circulation and may help understand the neuropathophysiological processes of various neurological diseases.

最近的调查显示,脑膜淋巴血管(mlv)沿着上矢状窦和横硬脑膜窦存在,它们将脑脊液(CSF)中的液体和免疫细胞排出到颈深部淋巴结。本研究使用免疫组织化学(IHC)和Western Blot技术显示mLV伴随人脑背侧(上矢状、下矢状、横、乙状和直)和基底(海绵窦、蝶顶窦、岩顶上和岩下)硬脑膜窦的存在。免疫组化样本取自3具尸体和3具尸体解剖的脊膜脊膜背窦和基底窦。对标本进行常规组织学检查。5µm厚石蜡切片采用Podoplanin (PDPN,淋巴管内皮细胞标志物)和CD31(血管内皮细胞标志物)免疫组化染色。此外,采用Western Blot方法对4例尸体解剖相同区域的组织样本进行PDPN和CD31蛋白的表达评估。每个鼻窦连续2个切片进行PDPN, CD31染色以区分血管(BV)和mLV。免疫组化染色显示硬脊膜窦背侧和基底侧均有mlv。与硬脑膜基底窦相比,伴随硬脑膜背窦的mlv具有更大的尺寸范围。然而,沿硬膜基底窦的mlv数量多于沿背窦的mlv数量。此外,流体通道紧密定位于mLV,具有不同的直径和密度。Western Blotting技术显示PDPN在脊膜窦背侧和基底侧均有表达。了解人类脊膜窦背侧和基底窦中mLV的存在可以增加对mLV如何促进脑淋巴循环的理解,并可能有助于理解各种神经系统疾病的神经病理生理过程。
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引用次数: 0
Suanzaoren decoction improves depressive-like behaviors by regulating the microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 inflammation signal pathway 酸枣仁汤通过抑制TLR4/NFκB/NLRP3炎症信号通路调节微生物群肠脑轴,改善抑郁样行为。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-23 DOI: 10.1016/j.jchemneu.2023.102349
Yiyang Du, Bosai He, Bo Wu, Tingxu Yan, Ying Jia

Depression is a common but serious sickness which causes a considerable burden on individuals and society. Recently, it has been well established that the occurrence of depression was related to the microbiota-gut-brain axis. The toll-like receptor 4 (TLR4)/ nuclear factor kappa-B kinase (NFκB)/ NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway is closely associated with the regulation of microbiota-gut-brain axis. Suanzaoren Decoction (SZRD), which recorded in Jin Gui Yao Lve in Han dynasty, has been used for treating insomnia and depression for a long time. However, the action mechanism of the depression regulation through the TLR4/NFκB/NLRP3 pathway by SZRD was still unclear. In this study, SZRD was firstly performed on a chronic unpredictable mild stress (CUMS) mice model. The results of behavioral tests showed that SZRD treatment could ameliorate the depressive-like behaviors of CUMS mice effectively. According to our previous researches about the components of SZRD in vitro and in vivo, the identification of serum metabolites in depression model rats was further analyzed qualitatively using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. 27 prototypes and 44 metabolites were identified. The main types of metabolic reactions are glucuronization, sulfation, and so on. Then, using immunohistochemistry and western blotting to monitor the difference in activation of TLR4/NFκB/NLRP3 signaling pathway in mice brain and colon. The results showed that SZRD treatment could reduce expression levels of related factors. Additionally, the SZRD treatment could also inhibit the histopathological damage in the path morphology of the hippocampus and colon. The results of 16SrRNA demonstrated that SZRD could reduce the dysbiosis of the intestinal flora of depressive mice. The above results provided important information for studying the action mechanism of SZRD in treating depression by regulating microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 pathway.

抑郁症是一种常见但严重的疾病,给个人和社会带来巨大负担。最近,抑郁症的发生与微生物群-肠-脑轴有关。toll样受体4(TLR4)/核因子κB激酶(NFκB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)通路与微生物群-肠-脑轴的调节密切相关。酸枣仁汤是汉代《金龟要略》中记载的一种治疗失眠、抑郁的药物,长期以来一直被人们广泛使用。然而,SZRD通过TLR4/NFκB/NLRP3通路调节抑郁症的作用机制尚不清楚。在本研究中,首次在慢性不可预测轻度应激(CUMS)小鼠模型上进行SZRD。行为测试结果表明,SZRD治疗能有效改善CUMS小鼠的抑郁样行为。根据我们以往对SZRD成分的体内外研究,采用超高效液相色谱-四极杆飞行时间质谱法对抑郁症模型大鼠血清代谢产物的鉴定进行了进一步的定性分析。鉴定出27个原型和44个代谢产物。代谢反应主要有葡萄糖醛酸化、硫酸化等。然后,利用免疫组织化学和蛋白质印迹法监测小鼠大脑和结肠中TLR4/NFκB/NLRP3信号通路激活的差异。结果表明,SZRD处理可降低相关因子的表达水平。此外,SZRD治疗还可以抑制海马和结肠通路形态的组织病理学损伤。16SrRNA检测结果表明,SZRD能减轻抑郁小鼠肠道菌群的失调。上述结果为研究SZRD通过抑制TLR4/NFκB/NLRP3通路调节微生物群肠脑轴治疗抑郁症的作用机制提供了重要信息。
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引用次数: 0
An investigation of the endoplasmic reticulum stress in obesity exposure in the prenatal period 产前肥胖暴露中内质网应激的研究。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-17 DOI: 10.1016/j.jchemneu.2023.102348
Kıymet Kübra Tüfekci̇ , Musa Tatar , Funda Terzi̇ , Elfide Gizem Bakirhan

Objectives

Exposure to maternal obesity has been shown to make offspring more prone to cognitive and metabolic disorders later in life. Although the underlying mechanisms are unclear, the role of endoplasmic reticulum (ER) stress in the fetal programming process is remarkable. ER stress can be activated by many chronic diseases, including obesity and diabetes. Therefore, our study aimed to investigate the role of ER stress caused by maternal diet-induced obesity in the offspring hippocampus. We also evaluated the protective effect of N-acetylcysteine (NAC) against ER stress.

Methods

A rat obesity model was created by providing a high-fat (60 % kcal) diet. N-acetylcysteine (NAC) was administered at a dosage of 150 mg/kg via the intragastric route. The animals were mated at the age of 12 weeks. The same diet was maintained during pregnancy and lactation. The experiment was terminated on the postnatal 28th day, and the offspring's brain tissues were examined. Immunohistochemical staining for ER stress markers was performed on sections taken from tissues after routine histological procedures.

Results

The results revealed increased GRP78, PERK, and eIF2α immunoreactivities in the hippocampal dentate gyrus (DG) and cornu ammonis 1 (CA1) regions in the obese group offspring, while the expression of those markers in those regions normalized with NAC supplementation (p < 0.01). Statistical analysis of XBP1 immunoreactivity H-scores revealed no difference between the study groups (p > 0.05).

Discussion

These results suggest that exposure to obesity during the prenatal period may cause increased ER stress in hippocampal neurons, which have an important role in the regulation of learning, memory and behavior, and this may contribute to decreased cognitive performance. On the other hand, NAC stands out as an effective agent that can counteract hippocampal ER stress.

目的:暴露于母体肥胖已被证明会使后代在以后的生活中更容易出现认知和代谢障碍。尽管其潜在机制尚不清楚,但内质网应激在胎儿编程过程中的作用是显著的。ER压力可被许多慢性疾病激活,包括肥胖和糖尿病。因此,我们的研究旨在探讨母亲饮食诱导的肥胖引起的ER应激在后代海马中的作用。我们还评估了N-乙酰半胱氨酸(NAC)对内质网应激的保护作用。方法:通过提供高脂肪(60%千卡)饮食建立大鼠肥胖模型。N-乙酰半胱氨酸(NAC)通过胃内途径以150mg/kg的剂量给药。这些动物在12周大时交配。在怀孕和哺乳期间保持相同的饮食。实验在出生后第28天终止,并对后代的脑组织进行检查。在常规组织学程序后对取自组织的切片进行ER应激标志物的免疫组织化学染色。结果:肥胖组子代海马齿状回(DG)和氨角1区(CA1)GRP78、PERK和eIF2α免疫反应活性增加,而这些标志物在补充NAC后这些区域的表达正常化(p0.05)。讨论:这些结果表明,产前暴露于肥胖可能会导致海马神经元的ER应激增加,而海马神经元在学习、记忆和行为的调节中起着重要作用,这可能会导致认知能力下降。另一方面,NAC是一种可以对抗海马ER应激的有效药物。
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引用次数: 0
Immunoreactivity of glutamine synthetase in satellite glia around various subpopulations of lumbar dorsal root ganglia neurons in adult rats treated with monosodium glutamate 谷氨酸单钠处理成年大鼠腰背根神经节神经元不同亚群周围卫星神经胶质中谷氨酰胺合成酶的免疫反应性。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-13 DOI: 10.1016/j.jchemneu.2023.102347
Aleksandra Krawczyk, Sylwia Mozel, Karol Rycerz, Jadwiga Jaworska-Adamu, Marcin Bartłomiej Arciszewski

Satellite glial cells (SGCs), involved inter alia in glutamate (Glu) metabolism, form a glial sheath around sensory neurons of dorsal root ganglia (DRGs). SGCs show a presence of glutamine synthetase (GS) which transform uptaken Glu into glutamine (Gln). In DRGs, this aminoacid is used mainly by small neurons which are able to synthetize substance P (SP) that play a crucial role in nociception. The aim of the study was to define the influence of monosodium glutamate (MSG) on GS immunoreactivity in satellite glia around various subpopulations of neurons including SP immunopositive cells in DRGs of adult rats. The studies were carried out on lumbar DRGs slides in rats which received subcutaneous injection of saline solution (control group) or 4 g/kg b. w. of MSG (MSG group). Immunofluorescence reactions were conducted with use of anti-GS and anti-SP antibodies. Administration of MSG to adult rats increased the GS immunoexpression in SGCs. In rats receiving MSG, a number of small neurons with GS-immunopositive glial sheath was not altered when compared to control individuals, whereas there was a statistically significant increase of GS immunoexpression in SGCs around large and medium neurons. Moreover, in these animals, a statistically significant increase in the number of small SP-positive neurons with GS-positive glial sheath was observed. SP is responsible for transmission of pain, thus the obtained results may be useful for further research concerning the roles of glia in nociceptive pathway regulation.

卫星神经胶质细胞(SGCs)参与谷氨酸(Glu)代谢,在背根神经节(DRGs)的感觉神经元周围形成神经胶质鞘。SGCs表现出谷氨酰胺合成酶(GS)的存在,其将摄取的Glu转化为谷氨酰胺(Gln)。在DRG中,这种氨基酸主要由小神经元使用,这些神经元能够合成在伤害感受中起关键作用的物质P(SP)。本研究的目的是确定谷氨酸一钠(MSG)对成年大鼠DRG中包括SP免疫阳性细胞在内的各种神经元亚群周围卫星神经胶质中GS免疫反应性的影响。本研究在接受皮下注射生理盐水(对照组)或4g/kg b.w.MSG(MSG组)的大鼠的腰椎DRG载玻片上进行。使用抗GS和抗SP抗体进行免疫荧光反应。对成年大鼠施用MSG增加了SGCs中GS的免疫表达。在接受MSG的大鼠中,与对照个体相比,许多具有GS免疫阳性神经胶质鞘的小神经元没有改变,而在大神经元和中神经元周围的SGCs中,GS免疫表达在统计学上显著增加。此外,在这些动物中,观察到具有GS阳性神经胶质鞘的小SP阳性神经元的数量在统计学上显著增加。SP负责疼痛的传递,因此所获得的结果可能有助于进一步研究神经胶质在伤害性通路调节中的作用。
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引用次数: 0
Ginsenoside Rg2 alleviates neurovascular damage in 3xTg-AD mice with Alzheimer's disease through the MAPK-ERK pathway 人参皂苷Rg2通过MAPK-ERK途径减轻患有阿尔茨海默病的3xTg AD小鼠的神经血管损伤。
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-05 DOI: 10.1016/j.jchemneu.2023.102346
Xiaojun Ye , Sen Shao , Yanbo Wang , Wenwen Su

Alzheimer's disease (AD) is the most common form of dementia, and ginsenoside Rg2 (Rg2) is proven to inhibit AD’s progression. This study investigates the potential benefits of Rg2 treatment on 3xTg-AD mice. Following 6 weeks of gavage treatment, Rg2-treated 3xTg-AD mice exhibited improved spatial recognition memory behaviors, regional cerebral blood flow, and histopathological injury of the hippocampus, which were observed through a Y-maze test, laser Doppler flowmetry, and hematoxylin-eosin staining. Additionally, Rg2 treatment caused a decrease in the levels of amyloid beta 25–35, TNF-α, IL-1β, and IL-6, as measured by enzyme-linked immunosorbent assay, as well as a reduction in mRNA levels of IL-1β and IL-6 in 3xTg-AD mouse brains using quantitative real-time PCR. In particular, NeuN and CD31 levels were inhibited and GFAP level was elevated in 3xTg-AD mice that were observed through immunofluorescence, and these levels were all antagonized by Rg2, suggesting the effects of Rg2 on neurovascular damage, astrocyte activation, and neuronal loss. Furthermore, Western blot and qRT-PCR assays showed that Rg2 blocked the expression of ICAM-1 and VCAM-1 in 3xTg-AD mice. By Western blot, the ratios of p-ERK/ERK and p-MAPK/MAPK in 3xTg-AD mice were upregulated by Rg2 treatment, suggesting the neuroprotective effects of Rg2 may be related to the MAPK-ERK pathway. In summary, this study demonstrated the potential of Rg2 to improve AD and provided a scientific basis for research on the biological mechanism of AD and the development of Rg2.

阿尔茨海默病(AD)是最常见的痴呆形式,人参皂苷Rg2(Rg2)被证明可以抑制AD的进展。本研究调查了Rg2治疗3xTg AD小鼠的潜在益处。灌胃治疗6周后,Rg2处理的3xTg AD小鼠表现出改善的空间识别记忆行为、局部脑血流量和海马组织病理学损伤,这是通过Y迷宫测试、激光多普勒流量计和苏木精-伊红染色观察到的。此外,Rg2治疗导致3xTg AD小鼠大脑中淀粉样蛋白β25-35、TNF-α、IL-1β和IL-6水平下降,如酶联免疫吸附测定所测,以及IL-1β、IL-6 mRNA水平下降。特别是,在通过免疫荧光观察到的3xTg AD小鼠中,NeuN和CD31水平被抑制,GFAP水平升高,并且这些水平都被Rg2拮抗,这表明Rg2对神经血管损伤、星形胶质细胞活化和神经元损失的影响。此外,Western印迹和qRT-PCR分析显示Rg2阻断了3xTg AD小鼠中ICAM-1和VCAM-1的表达。通过蛋白质印迹,Rg2处理可上调3xTg AD小鼠的p-ERK/ERK和p-MAPK/MAPK的比例,表明Rg2的神经保护作用可能与MAPK-ERK通路有关。总之,本研究展示了Rg2改善AD的潜力,为研究AD的生物学机制和Rg2的发展提供了科学依据。
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引用次数: 0
Aripiprazole attenuates the medial prefrontal cortex morphological and biochemical alterations in rats with neonatal ventral hippocampus lesion 阿立哌唑可减轻新生海马腹侧病变大鼠内侧前额叶皮层形态学和生化改变
IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-01 DOI: 10.1016/j.jchemneu.2023.102316
Gabriel D. Flores-Gómez , David Javier Apam-Castillejos , Ismael Juárez-Díaz , Estefania Fuentes-Medel , Alfonso Díaz , Hiram Tendilla-Beltrán , Gonzalo Flores

Schizophrenia is a neurodevelopmental disorder characterized by a loss of dendritic spines in the medial prefrontal cortex (mPFC). Multiple subclinical and clinical studies have evidenced the ability of antipsychotics to improve neuroplasticity. In this study, it was evaluated the effect of the atypical antipsychotic aripiprazole (ARI) on the behavioral and mPFC neuronal disturbances of rats with neonatal ventral hippocampus lesion (nVHL), which is a heuristic developmental model relevant to the study of schizophrenia. ARI attenuated open field hyperlocomotion in the rats with nVHL. Also, ARI ameliorated structural neuroplasticity disturbances of the mPFC layer 3 pyramidal cells, but not in the layer 5 neurons. These effects can be associated with the ARI capability of increasing brain-derived neurotrophic factor (BDNF) levels. Moreover, in the animals with nVHL, ARI attenuated the immunoreactivity for some oxidative stress-related molecules such as the nitric oxide synthase 2 (NOS-2), 3-nitrotyrosine (3-NT), and cyclooxygenase 2 (COX-2), as well as the reactive astrogliosis in the mPFC. These results contribute to current knowledge about the neurotrophic, anti-inflammatory, and antioxidant properties of antipsychotics which may be contributing to their clinical effects and envision promising therapeutic targets for the treatment of schizophrenia.

精神分裂症是一种以内侧前额叶皮层(mPFC)树突棘缺失为特征的神经发育障碍。多项亚临床和临床研究证明了抗精神病药物改善神经可塑性的能力。在本研究中,评估了非典型抗精神病药物阿立哌唑(ARI)对新生儿腹侧海马损伤(nVL)大鼠行为和mPFC神经元紊乱的影响,这是一种与精神分裂症研究相关的启发式发展模型。ARI减弱了nVL大鼠的开放性超运动。此外,ARI改善了mPFC第3层锥体细胞的结构神经可塑性紊乱,但在第5层神经元中没有改善。这些作用可能与ARI增加脑源性神经营养因子(BDNF)水平的能力有关。此外,在患有nVHL的动物中,ARI减弱了一些氧化应激相关分子的免疫反应性,如一氧化氮合酶2(NOS-2)、3-硝基酪氨酸(3-NT)和环氧化酶2(COX-2),以及mPFC中的反应性星形胶质细胞增生。这些结果有助于了解抗精神病药物的神经营养、抗炎和抗氧化特性,这可能有助于其临床效果,并有望成为治疗精神分裂症的有希望的治疗靶点。
{"title":"Aripiprazole attenuates the medial prefrontal cortex morphological and biochemical alterations in rats with neonatal ventral hippocampus lesion","authors":"Gabriel D. Flores-Gómez ,&nbsp;David Javier Apam-Castillejos ,&nbsp;Ismael Juárez-Díaz ,&nbsp;Estefania Fuentes-Medel ,&nbsp;Alfonso Díaz ,&nbsp;Hiram Tendilla-Beltrán ,&nbsp;Gonzalo Flores","doi":"10.1016/j.jchemneu.2023.102316","DOIUrl":"10.1016/j.jchemneu.2023.102316","url":null,"abstract":"<div><p><span><span>Schizophrenia<span><span> is a neurodevelopmental disorder characterized by a loss of </span>dendritic spines in the medial prefrontal cortex (mPFC). Multiple subclinical and clinical studies have evidenced the ability of </span></span>antipsychotics<span><span> to improve neuroplasticity<span><span>. In this study, it was evaluated the effect of the atypical antipsychotic </span>aripiprazole<span> (ARI) on the behavioral and mPFC neuronal disturbances of rats with neonatal ventral hippocampus lesion (nVHL), which is a heuristic developmental model relevant to the study of schizophrenia. ARI attenuated open field hyperlocomotion in the rats with nVHL. Also, ARI ameliorated structural neuroplasticity disturbances of the mPFC layer 3 </span></span></span>pyramidal cells<span><span>, but not in the layer 5 neurons. These effects can be associated with the ARI capability of increasing brain-derived neurotrophic factor (BDNF) levels. Moreover, in the animals with nVHL, ARI attenuated the immunoreactivity for some oxidative stress-related molecules such as the </span>nitric oxide synthase 2 (NOS-2), 3-nitrotyrosine (3-NT), and </span></span></span>cyclooxygenase<span><span> 2 (COX-2), as well as the reactive astrogliosis in the mPFC. These results contribute to current knowledge about the neurotrophic, anti-inflammatory, and antioxidant properties of antipsychotics which may be contributing to their clinical effects and envision promising therapeutic targets for the </span>treatment of schizophrenia.</span></p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"132 ","pages":"Article 102316"},"PeriodicalIF":2.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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Journal of chemical neuroanatomy
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