Pub Date : 2024-03-13DOI: 10.1016/j.jchemneu.2024.102414
Qian Tang , Ryota Ojiro , Shunsuke Ozawa , Xinyu Zou , Junta Nakahara , Tomohiro Nakao , Mihoko Koyanagi , Meilan Jin , Toshinori Yoshida , Makoto Shibutani
Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of Gpr150, Mmp23, Rprml, and Pcdh8 as well as the hypomethylation and upregulation of Ppm1j, Fam222a, and Opn3. Immunohistochemically, reprimo-like+ hilar cells and protocadherin-8+ granule cells were decreased and opsin-3+ hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67+ γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by Ctnnb1 and Syp upregulation and Mapk14, Map2k3, and Grip1 downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.
从胚胎阶段就暴露于姜黄素(CUR)无定形配方的大鼠后代具有抗焦虑样行为、增强的恐惧消除学习能力以及海马齿状回(DG)突触可塑性的增强。在本研究中,我们研究了神经源龛中甲基化状态改变的基因与 CUR 暴露后神经功能增强之间的联系。我们在大鼠分娩后第 77 天对暴露于 CUR 的后代进行了 DG 甲基化和 RNA 测序分析。甲基化敏感的高分辨率熔解和实时逆转录 PCR 分别验证了候选基因的甲基化状态和转录水平。在CUR组中,我们证实了Gpr150、Mmp23、Rprml和Pcdh8的高甲基化和下调,以及Ppm1j、Fam222a和Opn3的低甲基化和上调。免疫组化显示,暴露于 CUR 后,reprimo-like+柱状细胞和protocadherin-8+颗粒细胞减少,opsin-3+柱状细胞增加。谷氨酸脱羧酶 67+ γ-氨基丁酸能中间神经元亚群上部分表达了reprimo-like和opsin-3。此外,参与原粘连蛋白-8 介导的 N-粘连蛋白内吞的基因转录水平也随着 CUR 的暴露而改变;与此同时,Ctnnb1 和 Syp 上调,Mapk14、Map2k3 和 Grip1 下调,这表明 CUR 诱导的突触可塑性增强与细胞粘附有关。总之,我们的研究结果表明,在海马神经源龛的不同神经元群中,功能不同的基因的甲基化和表达发生了改变,从而增强了暴露于 CUR 后的突触可塑性。
{"title":"DNA methylation-altered genes in the rat hippocampal neurogenic niche after continuous exposure to amorphous curcumin","authors":"Qian Tang , Ryota Ojiro , Shunsuke Ozawa , Xinyu Zou , Junta Nakahara , Tomohiro Nakao , Mihoko Koyanagi , Meilan Jin , Toshinori Yoshida , Makoto Shibutani","doi":"10.1016/j.jchemneu.2024.102414","DOIUrl":"10.1016/j.jchemneu.2024.102414","url":null,"abstract":"<div><p>Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of <em>Gpr150</em>, <em>Mmp23</em>, <em>Rprml</em>, and <em>Pcdh8</em> as well as the hypomethylation and upregulation of <em>Ppm1j</em>, <em>Fam222a</em>, and <em>Opn3</em>. Immunohistochemically, reprimo-like<sup>+</sup> hilar cells and protocadherin-8<sup>+</sup> granule cells were decreased and opsin-3<sup>+</sup> hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67<sup>+</sup> γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by <em>Ctnnb1</em> and <em>Syp</em> upregulation and <em>Mapk14</em>, <em>Map2k3</em>, and <em>Grip1</em> downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102414"},"PeriodicalIF":2.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136814","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}
Pub Date : 2024-03-07DOI: 10.1016/j.jchemneu.2024.102412
Sara Mohamed Naguib Abdel Hafez , El-Shimaa M.N. abdelhafez
Organ damage brought on by ischemia is exacerbated by the reperfusion process. L-cysteine is a semi-essential amino acid that acts as a substrate for cystathionine-β-synthase in the central nervous system. The aim of this study was to investigate the possible protective effects of L- cysteine against the structural and biochemical changes that occur in the rat sciatic nerve after ischemia reperfusion (I/R) and to address some of the underlying mechanisms of these effects. Rats were divided into 4 groups: sham, l-cysteine, I/R, and l-cysteine- I/R groups. Specimens of sciatic nerve were processed for biochemical, histological, and immunohistochemical assessment. The results showed in I/R group, a significant increase in malondialdehyde with a significant decrease in both Nuclear respiratory factor-1 (NRF1) and superoxide dismutase levels. Moreover, with histological alteration. There was a significant increase in the mean surface area fraction of anti-caspase immunopositive cells as well as a significantdecrease in mean surface area fraction of anti-CD 34 immunopositive cells. In contrast, the l-cysteine- I/R group showed amelioration of these biochemical, structural, and immunohistochemical changes. To the best of our knowledge, this is the first study showed the protective effects of l-cysteine in sciatic nerve I/R via NRF1and caspase 3 modulation as well as telocyte activation.
{"title":"The possible protective effect of l-cysteine in a rat model of sciatic nerve ischemia-reperfusion: A possible role for NRF1 and Caspase 3; Biochemical, Histological, and Immunohistochemical study","authors":"Sara Mohamed Naguib Abdel Hafez , El-Shimaa M.N. abdelhafez","doi":"10.1016/j.jchemneu.2024.102412","DOIUrl":"10.1016/j.jchemneu.2024.102412","url":null,"abstract":"<div><p>Organ damage brought on by ischemia is exacerbated by the reperfusion process. L-cysteine is a semi-essential amino acid that acts as a substrate for cystathionine-β-synthase in the central nervous system. The aim of this study was to investigate the possible protective effects of L- cysteine against the structural and biochemical changes that occur in the rat sciatic nerve after ischemia reperfusion (I/R) and to address some of the underlying mechanisms of these effects. Rats were divided into 4 groups: sham, l-cysteine, I/R, and l-cysteine- I/R groups. Specimens of sciatic nerve were processed for biochemical, histological, and immunohistochemical assessment. The results showed in I/R group, a significant increase in malondialdehyde with a significant decrease in both Nuclear respiratory factor-1 (NRF1) and superoxide dismutase levels. Moreover, with histological alteration. There was a significant increase in the mean surface area fraction of anti-caspase immunopositive cells as well as a significantdecrease in mean surface area fraction of anti-CD 34 immunopositive cells. In contrast, the l-cysteine- I/R group showed amelioration of these biochemical, structural, and immunohistochemical changes. To the best of our knowledge, this is the first study showed the protective effects of l-cysteine in sciatic nerve I/R <em>via</em> NRF1and caspase 3 modulation as well as telocyte activation.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102412"},"PeriodicalIF":2.8,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068421","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}
Pub Date : 2024-03-06DOI: 10.1016/j.jchemneu.2024.102403
Janine C.M. Jaramillo , Connor M. Aitken , Andrew J. Lawrence , Philip J. Ryan
Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (OxtrPBN) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of OxtrPBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of OxtrPBN neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating OxtrPBN neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders.
{"title":"Oxytocin-receptor-expressing neurons in the lateral parabrachial nucleus activate widespread brain regions predominantly involved in fluid satiation","authors":"Janine C.M. Jaramillo , Connor M. Aitken , Andrew J. Lawrence , Philip J. Ryan","doi":"10.1016/j.jchemneu.2024.102403","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102403","url":null,"abstract":"<div><p>Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (Oxtr<sup>PBN</sup>) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of Oxtr<sup>PBN</sup> neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of Oxtr<sup>PBN</sup> neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating Oxtr<sup>PBN</sup> neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102403"},"PeriodicalIF":2.8,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041703","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}
Pub Date : 2024-03-04DOI: 10.1016/j.jchemneu.2024.102405
Hamza Mohamed , Omur Gulsum Deniz , Suleyman Kaplan
This study investigated the potential effects on the hippocampus of electromagnetic fields (EMFs) disseminated by mobile phones and the roles of baobab (Adansonia digitata) (AD) and black seed (Nigella sativa) (BS) in mitigating these. Fifty-six male, 12-week-old Wistar albino rats were divided into eight groups of seven animals each. No EMF exposure was applied to the control, AD or BS groups, while the rats in the Sham group were placed in an EMF system with no exposure. A 900-MHz EMF was applied to the EMF+AD, EMF+BS, EMF+AD+BS and EMF groups for 1 hour a day for 28 days. Pyramidal neurons in the hippocampus were subsequently counted using the optical fractionator technique, one of the unbiased stereological methods. Tissue sections were also evaluated histopathologically under light and electron microscopy. The activities of the enzymes catalase (CAT) and superoxide dismutase (SOD) were also determined in blood serum samples. Analysis of the stereological data revealed no statistically significant differences between the EMF and control or sham groups in terms of pyramidal neuron numbers (p>0.05). However, stereological examination revealed a crucial difference in the entire hippocampus between the control group and the AD (p<0.01) and BS (p<0.05) groups. Moreover, exposure to 900-MHz EMF produced adverse changes in the structures of neurons at histopathological analysis. Qualitative examinations suggest that a combination of herbal products such as AD and BS exerts a protective effect against such EMF side-effects.
{"title":"The neuroprotective effects of baobab and black seed on the rat hippocampus exposed to a 900-MHz electromagnetic field","authors":"Hamza Mohamed , Omur Gulsum Deniz , Suleyman Kaplan","doi":"10.1016/j.jchemneu.2024.102405","DOIUrl":"10.1016/j.jchemneu.2024.102405","url":null,"abstract":"<div><p>This study investigated the potential effects on the hippocampus of electromagnetic fields (EMFs) disseminated by mobile phones and the roles of baobab (<em>Adansonia digitata</em>) (AD) and black seed (<em>Nigella sativa</em>) (BS) in mitigating these. Fifty-six male, 12-week-old <em>Wistar albino</em> rats were divided into eight groups of seven animals each. No EMF exposure was applied to the control, AD or BS groups, while the rats in the Sham group were placed in an EMF system with no exposure. A 900-MHz EMF was applied to the EMF+AD, EMF+BS, EMF+AD+BS and EMF groups for 1 hour a day for 28 days. Pyramidal neurons in the hippocampus were subsequently counted using the optical fractionator technique, one of the unbiased stereological methods. Tissue sections were also evaluated histopathologically under light and electron microscopy. The activities of the enzymes catalase (CAT) and superoxide dismutase (SOD) were also determined in blood serum samples. Analysis of the stereological data revealed no statistically significant differences between the EMF and control or sham groups in terms of pyramidal neuron numbers (p>0.05). However, stereological examination revealed a crucial difference in the entire hippocampus between the control group and the AD (p<0.01) and BS (p<0.05) groups. Moreover, exposure to 900-MHz EMF produced adverse changes in the structures of neurons at histopathological analysis. Qualitative examinations suggest that a combination of herbal products such as AD and BS exerts a protective effect against such EMF side-effects.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102405"},"PeriodicalIF":2.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049631","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}
Pub Date : 2024-02-28DOI: 10.1016/j.jchemneu.2024.102402
Rademene S. Oria , Godson E. Anyanwu , Johnson N. Nto , James O. Ikpa
Curcumin, a bioactive polyphenol derived from turmeric, has been reported to have anti-inflammatory properties. The current study investigated the anti-inflammatory effect of curcumin in the hippocampal subfields (CA1 and CA3) after exposure to cobalt (Co) and the impact of ERK protein. Twenty-eight albino Wistar rats were divided into four groups, each with seven randomly selected rats as follows: Control (distilled water), Cobalt (Co) only (40 mg/kg), 120 mg/kg or 240 mg/kg curcumin + Co (40 mg/kg). Treatment was via oral gavage for 28 days. We performed a biochemical investigation to determine the levels of proinflammatory cytokines (TNFα and IL-1β). Furthermore, we conducted an immunohistochemical evaluation to assess the expression of IBA1 by microglial cells and the immunoexpression of ERK protein in the hippocampus. Results revealed a significant (p<0.05) elevation in the tissue level of TNFα and IL-1β, an increase in the number of IBA1-positive microglia, and upregulation of ERK protein in the hippocampal subfields of the rats after exposure to cobalt-only. Nevertheless, pretreatment with curcumin restored these parameters to levels comparable to control. In conclusion, our results showed that curcumin abrogated the Co-induced neuroinflammation by suppressing the release of proinflammatory biomarkers, reducing microgliosis, and modulating the ERK/MAPK pathway.
{"title":"Curcumin abrogates cobalt-induced neuroinflammation by suppressing proinflammatory cytokines release, inhibiting microgliosis and modulation of ERK/MAPK signaling pathway","authors":"Rademene S. Oria , Godson E. Anyanwu , Johnson N. Nto , James O. Ikpa","doi":"10.1016/j.jchemneu.2024.102402","DOIUrl":"10.1016/j.jchemneu.2024.102402","url":null,"abstract":"<div><p>Curcumin, a bioactive polyphenol derived from turmeric, has been reported to have anti-inflammatory properties. The current study investigated the anti-inflammatory effect of curcumin in the hippocampal subfields (CA1 and CA3) after exposure to cobalt (Co) and the impact of ERK protein. Twenty-eight albino Wistar rats were divided into four groups, each with seven randomly selected rats as follows: Control (distilled water), Cobalt (Co) only (40 mg/kg), 120 mg/kg or 240 mg/kg curcumin + Co (40 mg/kg). Treatment was via oral gavage for 28 days. We performed a biochemical investigation to determine the levels of proinflammatory cytokines (TNFα and IL-1β). Furthermore, we conducted an immunohistochemical evaluation to assess the expression of IBA1 by microglial cells and the immunoexpression of ERK protein in the hippocampus. Results revealed a significant (p<0.05) elevation in the tissue level of TNFα and IL-1β, an increase in the number of IBA1-positive microglia, and upregulation of ERK protein in the hippocampal subfields of the rats after exposure to cobalt-only. Nevertheless, pretreatment with curcumin restored these parameters to levels comparable to control. In conclusion, our results showed that curcumin abrogated the Co-induced neuroinflammation by suppressing the release of proinflammatory biomarkers, reducing microgliosis, and modulating the ERK/MAPK pathway.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102402"},"PeriodicalIF":2.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002722","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}
Pub Date : 2024-02-27DOI: 10.1016/j.jchemneu.2024.102404
Linli Guo , Yanan Zhao , Zhengqiao Kong , Ruihua Liu , Ping Liu
Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aβ1–42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aβ, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aβ1–42/Al3+ through anti-oxidative stress and anti-apoptotic features.
阿尔茨海默病(AD)是一种神经系统退行性疾病,发病机制尚不清楚。单靶点药物治疗阿尔茨海默病的疗效非常有限,而合成的多靶点药物疗效和安全性都很差。因此,寻找合适的天然多靶点药物来治疗注意力缺失症是一项非常有意义的研究。我们选择了两种黄酮醇,即 myricetin 和 morin,进行相关研究。在这项研究中,我们采用向大鼠海马 CA1 区显微注射 Aβ1-42 低聚物,并结合灌胃六水氯化铝(AlCl3-6H2O)溶液的方法建立了 AD 大鼠模型,并选择了杨梅素和吗啉作为干预药物,以探讨它们对神经损伤的保护作用。实验结果表明,制霉菌素和吗啉能减少大鼠脑内Aβ、Tau和磷酸化Tau的产生,下调相关炎症因子的表达,减少海马细胞凋亡。脑组织中三磷酸腺苷酶、过氧化氢酶、总超氧化物歧化酶的活性和谷胱甘肽的含量都有明显提高。然而,脑组织中丙二醛的含量、诱导型一氧化氮合酶和乙酰胆碱酯酶的活性则有所下降。这两种黄酮可以调节单胺和氨基酸神经递质水平的失衡。总之,杨梅素或吗啉可通过抗氧化应激和抗细胞凋亡功能有效改善 Aβ1-42/Al3+ 诱导的 AD 大鼠的学习和记忆功能障碍。
{"title":"Protective effects of myricetin and morin on neurological damage in Aβ1–42/Al3+ -induced Alzheimer’s disease model of rats","authors":"Linli Guo , Yanan Zhao , Zhengqiao Kong , Ruihua Liu , Ping Liu","doi":"10.1016/j.jchemneu.2024.102404","DOIUrl":"10.1016/j.jchemneu.2024.102404","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aβ<sub>1–42</sub> oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl<sub>3</sub>·6H<sub>2</sub>O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aβ, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aβ<sub>1–42</sub>/Al<sup>3+</sup> through anti-oxidative stress and anti-apoptotic features.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102404"},"PeriodicalIF":2.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996381","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}
Pub Date : 2024-02-23DOI: 10.1016/j.jchemneu.2024.102399
Maryam Raoofi nejad , Elham Siasi , Mohammad Amin Abdollahifar , Abbas Aliaghaei
Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction results in movement disorders such as dysmetria, synergy and dysdiadochokinesia. This study investigates the therapeutic effects of elderberry (EB) diet on the 3-acetylpyridine-induced (3-AP) CA rat model. First, CA rat models were generated by 3-AP administration followed by elderberry diet treatment containing 2 % EB for 8 consecutive weeks. Motor performance, electromyographic activity and gene expression were then evaluated. The number of Purkinje neurons were evaluated by stereological methods. Immunohistochemistry for the microgliosis, astrogliosis and apoptosis marker caspase-3 was also performed. In addition, the morphology of microglia and astrocytes was assessed using the Sholl analysis method. The results showed that EB diet administration in a 3-AP ataxia model improved motor coordination, locomotor activity and neuro-muscular function, prevented Purkinje neurons degeneration, increased microglia and astrocyte complexity and reduced cell soma size. Moreover, EB diet administration decreased apoptosis in cerebellum of 3-AP ataxic model. In addition, elderberry diet treatment decreased the expression of inflammatory, apoptotic and necroptotic genes and increased the expression of antioxidant-related genes. The results suggest that the EB diet attenuates 3-AP-induced neuroinflammation leading to cell death and improves motor performance. Thus, the EB diet could be used as a therapeutic procedure for CA due to its neuroprotective effects.
{"title":"Elderberry diet enhances motor performance and reduces neuroinflammation-induced cell death in cerebellar ataxia rat models","authors":"Maryam Raoofi nejad , Elham Siasi , Mohammad Amin Abdollahifar , Abbas Aliaghaei","doi":"10.1016/j.jchemneu.2024.102399","DOIUrl":"10.1016/j.jchemneu.2024.102399","url":null,"abstract":"<div><p>Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction results in movement disorders such as dysmetria, synergy and dysdiadochokinesia. This study investigates the therapeutic effects of elderberry (EB) diet on the 3-acetylpyridine-induced (3-AP) CA rat model. First, CA rat models were generated by 3-AP administration followed by elderberry diet treatment containing 2 % EB for 8 consecutive weeks. Motor performance, electromyographic activity and gene expression were then evaluated. The number of Purkinje neurons were evaluated by stereological methods. Immunohistochemistry for the microgliosis, astrogliosis and apoptosis marker caspase-3 was also performed. In addition, the morphology of microglia and astrocytes was assessed using the Sholl analysis method. The results showed that EB diet administration in a 3-AP ataxia model improved motor coordination, locomotor activity and neuro-muscular function, prevented Purkinje neurons degeneration, increased microglia and astrocyte complexity and reduced cell soma size. Moreover, EB diet administration decreased apoptosis in cerebellum of 3-AP ataxic model. In addition, elderberry diet treatment decreased the expression of inflammatory, apoptotic and necroptotic genes and increased the expression of antioxidant-related genes. The results suggest that the EB diet attenuates 3-AP-induced neuroinflammation leading to cell death and improves motor performance. Thus, the EB diet could be used as a therapeutic procedure for CA due to its neuroprotective effects.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102399"},"PeriodicalIF":2.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944192","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}
Over time, scientists have been fascinated by the complex connections among nutrition, brain development, and behavior. It's been well understood that the brain's peak performance relies on having the right nutrients available. Thus, nutritional insufficiency, where an organism lacks vital nutrients crucial for optimal growth and function, can upset the body's balance, potentially triggering stress responses. However, our grasp of how the brain reacts to insufficient nutrition, particularly in avian species like domestic chickens, has shown inconsistencies in our understanding. Domestic chickens have frequently served as subjects for studying memory and learning, primarily focusing on the hippocampus—a region highly responsive to environmental changes. Yet, another critical brain region, the parahippocampal region, integral to memory and spatial cognition, had received relatively little attention concerning the consequences of inadequate nutrition and hydration. To address this knowledge gap, our study sought to investigate the impact of stress induced by nutritional insufficiency on the neuronal cells within the region parahippocampalis in two distinct age groups of domestic chickens, Gallus gallus domesticus: fifteen and thirty days old. We employed the Golgi-Cox-Impregnation technique to explore whether the structural characteristics of neuronal cells, specifically the dendritic spines, underwent changes under transient stressful conditions during these crucial developmental stages. The results were intriguing. Stress evidently induced observable alterations in the dendritic spines of the parahippocampal neuronal cells, with the extent of these changes being age-dependent. In fifteen-day-old chickens, stress prompted substantial modifications in the dendritic spines of parahippocampal multipolar and pyramidal neurons. In contrast, among thirty-day-old chickens, the response to stress was less comprehensive, with only specific parahippocampal multipolar neurons displaying such alterations. These findings underscored the influential role of stress in reshaping the structure of parahippocampal neurons and emphasized the importance of considering age when studying the impact of stress on the brain. Through this research, we aim to enhance our understanding of the intricate interplay between stress, brain structure, and the critical role of adequate nutrition, especially during pivotal developmental stages. Our future research objectives include a deeper investigation into the intracellular events including cellular and molecular mechanisms precipitating these changes and determining whether these alterations have downstream effects on crucial brain functions like learning and memory.
{"title":"Investigating the impact of nutritional insufficiency on parahippocampal neurons in domestic chickens, Gallus gallus domesticus","authors":"Adarsh Kumar , Kavita Tamta , Hemlata Arya , Shweta Arya , Ram Chandra Maurya","doi":"10.1016/j.jchemneu.2024.102401","DOIUrl":"10.1016/j.jchemneu.2024.102401","url":null,"abstract":"<div><p>Over time, scientists have been fascinated by the complex connections among nutrition, brain development, and behavior. It's been well understood that the brain's peak performance relies on having the right nutrients available. Thus, nutritional insufficiency, where an organism lacks vital nutrients crucial for optimal growth and function, can upset the body's balance, potentially triggering stress responses. However, our grasp of how the brain reacts to insufficient nutrition, particularly in avian species like domestic chickens, has shown inconsistencies in our understanding. Domestic chickens have frequently served as subjects for studying memory and learning, primarily focusing on the hippocampus—a region highly responsive to environmental changes. Yet, another critical brain region, the parahippocampal region, integral to memory and spatial cognition, had received relatively little attention concerning the consequences of inadequate nutrition and hydration. To address this knowledge gap, our study sought to investigate the impact of stress induced by nutritional insufficiency on the neuronal cells within the region parahippocampalis in two distinct age groups of domestic chickens, <em>Gallus gallus domesticus</em>: fifteen and thirty days old. We employed the Golgi-Cox-Impregnation technique to explore whether the structural characteristics of neuronal cells, specifically the dendritic spines, underwent changes under transient stressful conditions during these crucial developmental stages. The results were intriguing. Stress evidently induced observable alterations in the dendritic spines of the parahippocampal neuronal cells, with the extent of these changes being age-dependent. In fifteen-day-old chickens, stress prompted substantial modifications in the dendritic spines of parahippocampal multipolar and pyramidal neurons. In contrast, among thirty-day-old chickens, the response to stress was less comprehensive, with only specific parahippocampal multipolar neurons displaying such alterations. These findings underscored the influential role of stress in reshaping the structure of parahippocampal neurons and emphasized the importance of considering age when studying the impact of stress on the brain. Through this research, we aim to enhance our understanding of the intricate interplay between stress, brain structure, and the critical role of adequate nutrition, especially during pivotal developmental stages. Our future research objectives include a deeper investigation into the intracellular events including cellular and molecular mechanisms precipitating these changes and determining whether these alterations have downstream effects on crucial brain functions like learning and memory.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102401"},"PeriodicalIF":2.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921621","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}
Pub Date : 2024-02-09DOI: 10.1016/j.jchemneu.2024.102400
Artur Pałasz , Anna Lipiec-Borowicz , Aleksandra Suszka-Świtek , Julia Kistowska , Petra Horká , Andrzej Kaśkosz , Aneta Piwowarczyk-Nowak , John J. Worthington , Kinga Mordecka-Chamera
Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel regulatory peptides: spexin (SPX) and nesfatin-1 within the human claustrum. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. Nesfatin-1, a second pleiotropic neuropeptide, which is a derivative of the nucleobindin-2 (NUCB-2) protein, is characterized by a wide distribution in the brain. Nesfatin-1 is a substance with a strong anorexigenic effect, playing an important role in the neuronal circuits of the hypothalamus that regulate food intake and energy homeostasis. On the other hand, nesfatin-1 may be involved in several important brain functions such as sleep, reproductive behaviour, cognitive processes, stress responses and anxiety. For the first time we detected and described a population of nesfatin-1 and SPX expressing neurons in the human claustrum using immunohistochemical and fluorescent methods. The study presents the novel identification of SPX and nesfatin-1 immunopositive neurons in the human claustrum and their assemblies show similar patterns of distribution in the whole structure.
{"title":"Spexin and nesfatin-1-expressing neurons in the male human claustrum","authors":"Artur Pałasz , Anna Lipiec-Borowicz , Aleksandra Suszka-Świtek , Julia Kistowska , Petra Horká , Andrzej Kaśkosz , Aneta Piwowarczyk-Nowak , John J. Worthington , Kinga Mordecka-Chamera","doi":"10.1016/j.jchemneu.2024.102400","DOIUrl":"10.1016/j.jchemneu.2024.102400","url":null,"abstract":"<div><p>Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel regulatory peptides: spexin (SPX) and nesfatin-1 within the human claustrum. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. Nesfatin-1, a second pleiotropic neuropeptide, which is a derivative of the nucleobindin-2 (NUCB-2) protein, is characterized by a wide distribution in the brain. Nesfatin-1 is a substance with a strong anorexigenic effect, playing an important role in the neuronal circuits of the hypothalamus that regulate food intake and energy homeostasis. On the other hand, nesfatin-1 may be involved in several important brain functions such as sleep, reproductive behaviour, cognitive processes, stress responses and anxiety. For the first time we detected and described a population of nesfatin-1 and SPX expressing neurons in the human claustrum using immunohistochemical and fluorescent methods. The study presents the novel identification of SPX and nesfatin-1 immunopositive neurons in the human claustrum and their assemblies show similar patterns of distribution in the whole structure.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"136 ","pages":"Article 102400"},"PeriodicalIF":2.8,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717612","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}
Pub Date : 2024-02-09DOI: 10.1016/j.jchemneu.2024.102398
Amir Delavar , Fatemeh Rahimi Anbarkeh , Raheleh Baradaran , Zohreh Arab , Seyed Hamidreza Rastegar Moghaddam , Mahmoud Hosseini , Mohammad Reza Nikravesh , Shahin Saeidi Nejat , Mehdi Jalali
Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement.
二嗪农(DZN)是一种有机磷(OP),其最重要的作用机制是诱导氧化应激(OS)和抑制乙酰胆碱酯酶(AChE)。Verbascum cheiranthifolium(VER)和 Biebersteinia multifida(BM)分别属于 Scrophulariaceae 和 Biebersteiniaceae 科。这些植物因其有益功效而在伊朗传统医学中被广泛使用。因此,本研究旨在评估 VER 和 BM 的甲醇提取物对 DZN 治疗大鼠海马(HPC)中烟碱乙酰胆碱受体(nAChRs)α7 和 α4 亚基表达水平变化的保护作用。本研究使用了 36 只雄性 Wistar 大鼠,并将其随机分为六组:对照组、DZN(40mg/kg)组、VER(1g/kg)组、DZN+VER(40mg/kg+1g/kg)组、BM(150mg/kg)组和DZN+BM(40mg/kg+150mg/kg)组。治疗结束后,各组动物均进行莫里斯水迷宫(MWM)试验。对大鼠进行麻醉并抽血。最后,取出大鼠大脑进行组织学研究并评估操作系统参数。结果表明,DZN 增加了 HPC 中 nAChRs 的表达量,并显著抑制了胆碱酯酶(ChEs)活性和 OS 参数。此外,在 MWM 中,DZN 组找到平台的时间明显长于对照组,而探针测试的时间和距离则低于对照组。治疗组中的 VER 和 BM 提取物同时显著改善了 nAChRs 的表达程度、ChEs 活性以及 OS 和空间记忆的参数。总之,我们的研究结果支持 VER 和 BM 提取物相对于 DZN 对大鼠神经的保护作用。因此,VER 和 BM 的提取物可作为治疗学习障碍和增强记忆的一种有用方法。
{"title":"The protective effect of methanolic extract of Verbascum cheiranthifolium and Biebersteinia multifida DC on hippocampus damage induced by diazinon in male Wistar rats: An experimental study","authors":"Amir Delavar , Fatemeh Rahimi Anbarkeh , Raheleh Baradaran , Zohreh Arab , Seyed Hamidreza Rastegar Moghaddam , Mahmoud Hosseini , Mohammad Reza Nikravesh , Shahin Saeidi Nejat , Mehdi Jalali","doi":"10.1016/j.jchemneu.2024.102398","DOIUrl":"10.1016/j.jchemneu.2024.102398","url":null,"abstract":"<div><p>Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"137 ","pages":"Article 102398"},"PeriodicalIF":2.8,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717613","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}