Pub Date : 2024-10-31DOI: 10.1016/j.acthis.2024.152212
Lei Yan , Guangyue Luo , Chengxiang Han , Jialin Meng , Chaozhao Liang
This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.
{"title":"Exploring the oncogenic role of RGS19 in bladder cancer progression and prognosis","authors":"Lei Yan , Guangyue Luo , Chengxiang Han , Jialin Meng , Chaozhao Liang","doi":"10.1016/j.acthis.2024.152212","DOIUrl":"10.1016/j.acthis.2024.152212","url":null,"abstract":"<div><div>This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152212"},"PeriodicalIF":2.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.acthis.2024.152211
Wenquan Zhang , Min Du , Yingjian Jiang , Jiang Wang , Yue Yu , DianLiang Zhang
Background
Severe acute pancreatitis (SAP) is a common digestive system disorder in clinical practice, and it is often associated with liver damage in patients with severe acute pancreatitis. Several studies have indicated that pyroptosis plays a role in liver damage following severe acute pancreatitis (SAP). However, the precise mechanisms remain unclear. This study aims to elucidate the association and specific mechanisms between liver injury following SAP and pyroptosis, providing theoretical support for research on SAP-induced liver injury.
Methods
A rat model of SAP with concomitant liver injury was successfully established. The expression levels of miR-103–3p across different liver tissue groups were quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Bioinformatic analyses and dual-luciferase reporter assays confirmed that NLRP1 is a direct target of miR-103–3p. In vivo assessments of miR-103–3p levels were performed, and the extent of cell pyroptosis during liver injury post-SAP was evaluated through western blotting, qRT-PCR, scanning electron microscopy, histopathology, immunofluorescence, and immunohistochemistry. The role of miR-103–3p in regulating NLRP1-mediated pyroptosis and its impact on SAP-induced liver injury were validated.
Results
This study reports that following SAP-induced liver injury, the expression of miR-103–3p in liver tissue was significantly decreased, and cell pyroptosis was involved in the process of liver injury. Experimental validation indicated that NLRP1 was a downstream target of miR-103–3p. Overexpression of miR-103–3p in vitro significantly alleviated the severity of liver injury following SAP, while simultaneously inhibiting cell pyroptosis.
Conclusion
These findings indicate that pyroptosis may be linked to SAP-induced liver injury and that miR-103–3p mitigates hepatocyte pyroptosis by reducing liver injury through the suppression of NLRP1 expression.
背景：重症急性胰腺炎（SAP）是临床上常见的消化系统疾病，重症急性胰腺炎患者往往伴有肝损伤。一些研究表明，热蛋白沉积在重症急性胰腺炎（SAP）后的肝损伤中起一定作用。然而，其确切机制仍不清楚。本研究旨在阐明 SAP 后肝损伤与热蛋白沉积之间的关联和具体机制，为 SAP 诱导肝损伤的研究提供理论支持：方法：成功建立了伴有肝损伤的 SAP 大鼠模型。方法：成功建立了伴有肝损伤的 SAP 大鼠模型，并利用定量反转录聚合酶链反应（qRT-PCR）对不同肝组织组 miR-103-3p 的表达水平进行了定量分析。生物信息学分析和双荧光素酶报告实验证实，NLRP1 是 miR-103-3p 的直接靶标。研究人员对 miR-103-3p 的水平进行了体内评估，并通过 Western 印迹、qRT-PCR、扫描电子显微镜、组织病理学、免疫荧光和免疫组织化学等方法评估了 SAP 后肝损伤过程中细胞热解的程度。研究验证了 miR-103-3p 在调控 NLRP1 介导的热蛋白沉积中的作用及其对 SAP 诱导的肝损伤的影响：结果：本研究发现，SAP 诱导的肝损伤后，肝组织中 miR-103-3p 的表达明显降低，细胞裂解参与了肝损伤的过程。实验验证表明，NLRP1是miR-103-3p的下游靶标。在体外过表达 miR-103-3p 能明显减轻 SAP 损伤后肝损伤的严重程度，同时抑制细胞嗜热：这些研究结果表明，肝细胞脓毒症可能与 SAP 诱导的肝损伤有关，而 miR-103-3p 可通过抑制 NLRP1 的表达减轻肝损伤，从而缓解肝细胞脓毒症。
{"title":"miR-103–3p attenuates liver injury with severe acute pancreatitis by inhibiting pyroptosis through miR-103–3p/NLRP1 axis","authors":"Wenquan Zhang , Min Du , Yingjian Jiang , Jiang Wang , Yue Yu , DianLiang Zhang","doi":"10.1016/j.acthis.2024.152211","DOIUrl":"10.1016/j.acthis.2024.152211","url":null,"abstract":"<div><h3>Background</h3><div>Severe acute pancreatitis (SAP) is a common digestive system disorder in clinical practice, and it is often associated with liver damage in patients with severe acute pancreatitis. Several studies have indicated that pyroptosis plays a role in liver damage following severe acute pancreatitis (SAP). However, the precise mechanisms remain unclear. This study aims to elucidate the association and specific mechanisms between liver injury following SAP and pyroptosis, providing theoretical support for research on SAP-induced liver injury.</div></div><div><h3>Methods</h3><div>A rat model of SAP with concomitant liver injury was successfully established. The expression levels of miR-103–3p across different liver tissue groups were quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Bioinformatic analyses and dual-luciferase reporter assays confirmed that NLRP1 is a direct target of miR-103–3p. In vivo assessments of miR-103–3p levels were performed, and the extent of cell pyroptosis during liver injury post-SAP was evaluated through western blotting, qRT-PCR, scanning electron microscopy, histopathology, immunofluorescence, and immunohistochemistry. The role of miR-103–3p in regulating NLRP1-mediated pyroptosis and its impact on SAP-induced liver injury were validated.</div></div><div><h3>Results</h3><div>This study reports that following SAP-induced liver injury, the expression of miR-103–3p in liver tissue was significantly decreased, and cell pyroptosis was involved in the process of liver injury. Experimental validation indicated that NLRP1 was a downstream target of miR-103–3p. Overexpression of miR-103–3p in vitro significantly alleviated the severity of liver injury following SAP, while simultaneously inhibiting cell pyroptosis.</div></div><div><h3>Conclusion</h3><div>These findings indicate that pyroptosis may be linked to SAP-induced liver injury and that miR-103–3p mitigates hepatocyte pyroptosis by reducing liver injury through the suppression of NLRP1 expression.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152211"},"PeriodicalIF":2.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.acthis.2024.152213
Lorenzo Alibardi
An electron microscopy and immunohistochemistry study has been conducted to acquire comparative information on the structure of apteric skin in ratites, ostrich and emu. The epidermis is thin in the neck of both species and thicker in the dorsal region where acidic and neutral keratins are present in the viable epidermis and stratum corneum. The dermis in both species is mostly occupied by collagen fibrils that form large bundles, often organized in alternated layers in the deeper part of the dermis. Numerous collagen fibrils contact the basement membrane of the epidermis. Sparse tactile Meissner or Krause sensilli are present among the thick collagen bundles. The ostrich epidermis in the dorsal skin is thicker than in the neck, with a columnar basal layer, 3–5 intermediate suprabasal layers and a thick corneous layer. The epidermis of the neck in emu is very thin, featuring two-three narrow cell layers above a flat basal layer and a relatively thick corneous layer. Basal and suprabasal keratinocytes contain lipid droplets and small keratin bundles but no keratohyalin accumulates in pre-corneous cells. The thin corneocytes form a multilayered corneous layer. Loricrine is present in pre-corneous and corneous layers while CBPs, formerly indicated as beta-keratins, are absent in apteric epidermis.
{"title":"Ultrastructure and immunohistochemistry of apteric skin in ratites and its epidermal soft cornification","authors":"Lorenzo Alibardi","doi":"10.1016/j.acthis.2024.152213","DOIUrl":"10.1016/j.acthis.2024.152213","url":null,"abstract":"<div><div>An electron microscopy and immunohistochemistry study has been conducted to acquire comparative information on the structure of apteric skin in ratites, ostrich and emu. The epidermis is thin in the neck of both species and thicker in the dorsal region where acidic and neutral keratins are present in the viable epidermis and stratum corneum. The dermis in both species is mostly occupied by collagen fibrils that form large bundles, often organized in alternated layers in the deeper part of the dermis. Numerous collagen fibrils contact the basement membrane of the epidermis. Sparse tactile Meissner or Krause sensilli are present among the thick collagen bundles. The ostrich epidermis in the dorsal skin is thicker than in the neck, with a columnar basal layer, 3–5 intermediate suprabasal layers and a thick corneous layer. The epidermis of the neck in emu is very thin, featuring two-three narrow cell layers above a flat basal layer and a relatively thick corneous layer. Basal and suprabasal keratinocytes contain lipid droplets and small keratin bundles but no keratohyalin accumulates in pre-corneous cells. The thin corneocytes form a multilayered corneous layer. Loricrine is present in pre-corneous and corneous layers while CBPs, formerly indicated as beta-keratins, are absent in apteric epidermis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152213"},"PeriodicalIF":2.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To date, no report has compared section thickness (ST) between the sliding microtome (SM) and rotary microtome (RM). We used the ice pack (IP) condition, in which the paraffin block was not cooled during slicing, and a continuous cooling device (CCD) for continuous cooling during slicing. The ST was greater for the SM than the RM in the IP condition, but it was identical between the devices under the CCD condition. Thus, we used the CCD condition for subsequent studies. In formalin-fixed, paraffin-embedded (FFPE) fish sausage blocks, the ST of the tissue surface (T-surface) was significantly concaved compared to that of the paraffin surface (P-surface) for both microtomes. On the contrary, in FFPE human kidney blocks, ST did not differ between the T-surface and P-surface. Furthermore, the eosin-positive area of PAM-stained specimens was affected by ST, and the color tone of the thickest sample differed from that of the median or thinnest sample. Our data indicated that we should use CCD conditions to ensure that ST is uniform regardless of the type of microtome. In addition, for quantitative analysis, we should utilize ST measure equipment and specimens with a constant ST.
迄今为止，还没有报告比较过滑动切片机（SM）和旋转切片机（RM）的切片厚度（ST）。我们使用了冰袋（IP）条件，即在切片过程中不冷却石蜡块，并使用持续冷却装置（CCD）在切片过程中持续冷却。在 IP 条件下，SM 的 ST 值大于 RM，但在 CCD 条件下，两种装置的 ST 值相同。因此，我们在后续研究中使用了 CCD 条件。在福尔马林固定、石蜡包埋（FFPE）的鱼肠块中，两种显微切片的组织表面（T 表面）的 ST 都比石蜡表面（P 表面）的 ST 明显凹陷。相反，在 FFPE 人肾组织块中，T 表面和 P 表面的 ST 没有差异。此外，PAM 染色样本的伊红阳性面积也受 ST 的影响，最厚样本的色调与中位样本或最薄样本的色调不同。我们的数据表明，无论使用哪种显微切片机，我们都应使用 CCD 条件来确保 ST 的一致性。此外，为了进行定量分析，我们应该使用 ST 测量设备和具有恒定 ST 的样本。
{"title":"Section thickness is identical for the sliding microtome and rotary microtome under the continuous cooling device condition","authors":"Mayuna Fukuzawa, Raia Kushibiki, Yuki Kanehira, Akifumi Ishizawa, Moe Kameda, Sayaka Kobayashi, Yoshimi Nishijima, Masanao Saio","doi":"10.1016/j.acthis.2024.152208","DOIUrl":"10.1016/j.acthis.2024.152208","url":null,"abstract":"<div><div>To date, no report has compared section thickness (ST) between the sliding microtome (SM) and rotary microtome (RM). We used the ice pack (IP) condition, in which the paraffin block was not cooled during slicing, and a continuous cooling device (CCD) for continuous cooling during slicing. The ST was greater for the SM than the RM in the IP condition, but it was identical between the devices under the CCD condition. Thus, we used the CCD condition for subsequent studies. In formalin-fixed, paraffin-embedded (FFPE) fish sausage blocks, the ST of the tissue surface (T-surface) was significantly concaved compared to that of the paraffin surface (P-surface) for both microtomes. On the contrary, in FFPE human kidney blocks, ST did not differ between the T-surface and P-surface. Furthermore, the eosin-positive area of PAM-stained specimens was affected by ST, and the color tone of the thickest sample differed from that of the median or thinnest sample. Our data indicated that we should use CCD conditions to ensure that ST is uniform regardless of the type of microtome. In addition, for quantitative analysis, we should utilize ST measure equipment and specimens with a constant ST.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152208"},"PeriodicalIF":2.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge.
Methods
On April 03, 2024, systematic searches were performed for papers in which histological analyses were conducted on skeletal muscle sampled from patients with HF or animal models of HF. Screening and data extraction were conducted by two independent authors.
Results and conclusion
A total of 118 papers were selected, including 33 human and 85 animal studies. Despite some disagreements among studies, some trends were observed. These trends included a slow-to-fast transition, a decrease in muscle fiber size, capillary to muscle fiber ratio, and mitochondrial activity and content, and an increase in apoptosis. These changes may contribute to the fatigability and decrease in muscle strength observed after HF. Although there were some disagreements between the results of human and animal studies, the results were generally similar. Animal models of HF will therefore be useful in elucidating the histological changes in skeletal muscle that occur in human patients with HF. Because the muscles subjected to histological analysis were mostly thigh muscles in humans and mostly lower leg muscles in animals, it remains uncertain whether changes similar to those seen in lower limb (hindlimb) muscles after HF also occur in upper limb (forelimb) muscles. The results of this review will consolidate the current knowledge on HF-induced histological changes in skeletal muscle and consequently aid in the rehabilitation of patients with HF and future studies.
{"title":"Histological changes in skeletal muscle induced by heart failure in human patients and animal models: A scoping review","authors":"Akinori Kaneguchi , Naoyoshi Sakitani , Takuya Umehara","doi":"10.1016/j.acthis.2024.152210","DOIUrl":"10.1016/j.acthis.2024.152210","url":null,"abstract":"<div><h3>Objective</h3><div>This scoping review aimed to characterize the histological changes in skeletal muscle after heart failure (HF) and to identify gaps in knowledge.</div></div><div><h3>Methods</h3><div>On April 03, 2024, systematic searches were performed for papers in which histological analyses were conducted on skeletal muscle sampled from patients with HF or animal models of HF. Screening and data extraction were conducted by two independent authors.</div></div><div><h3>Results and conclusion</h3><div>A total of 118 papers were selected, including 33 human and 85 animal studies. Despite some disagreements among studies, some trends were observed. These trends included a slow-to-fast transition, a decrease in muscle fiber size, capillary to muscle fiber ratio, and mitochondrial activity and content, and an increase in apoptosis. These changes may contribute to the fatigability and decrease in muscle strength observed after HF. Although there were some disagreements between the results of human and animal studies, the results were generally similar. Animal models of HF will therefore be useful in elucidating the histological changes in skeletal muscle that occur in human patients with HF. Because the muscles subjected to histological analysis were mostly thigh muscles in humans and mostly lower leg muscles in animals, it remains uncertain whether changes similar to those seen in lower limb (hindlimb) muscles after HF also occur in upper limb (forelimb) muscles. The results of this review will consolidate the current knowledge on HF-induced histological changes in skeletal muscle and consequently aid in the rehabilitation of patients with HF and future studies.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152210"},"PeriodicalIF":2.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1016/j.acthis.2024.152209
Thalles Fernando Rocha Ruiz , Luara Jesus Ferrato , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga
The elastic system is one of the most developed interstitial elements in connective tissue. With diverse functions, pre-elastic and elastic fibers contribute to the distensibility and malleability of several organs. Also, microanalyses of the elastic system were obtained by different histological techniques that were employed over years to describe normal and pathological conditions. Compared to conventional stains, hematoxylin-eosin/phloxine (HE/P) under fluorescence and confocal microscopy presented a highly detailed observation of the elastic system in different organs and scenarios. This technique provides a better demarcation of the elastic fibers, favoring their description in relation to their deposition and aggregation in different organs. Also, fibrils with low aggregation or loss of this characteristic are observed in an optimal view in the skin, heart valves, and large-caliber blood vessels. Degradation, fragmentation, and rupture were also well described by the HE/P technique. Several organs, such as the mammary gland, prostate, skin, aorta, and lung, could be described with precision under this technique. In association with non-linear microscopy, the results of the research presented in this paper improved and detailed characteristics of precise pathogenesis. Thus, the HE/P technique presented an interesting efficiency to demonstrate alterations and structures in which the elastic system showed a relevant role, and when compared to other techniques it demonstrated a similar or better result. In addition, it is expected that future studies can reveal more information about the elastin and interactions with specific dyes, thus allowing a greater understanding of the great efficiency of this technique.
{"title":"The elastic system: A review of elastin-related techniques and hematoxylin-eosin/phloxine applicability for normal and pathological tissue description","authors":"Thalles Fernando Rocha Ruiz , Luara Jesus Ferrato , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga","doi":"10.1016/j.acthis.2024.152209","DOIUrl":"10.1016/j.acthis.2024.152209","url":null,"abstract":"<div><div>The elastic system is one of the most developed interstitial elements in connective tissue. With diverse functions, pre-elastic and elastic fibers contribute to the distensibility and malleability of several organs. Also, microanalyses of the elastic system were obtained by different histological techniques that were employed over years to describe normal and pathological conditions. Compared to conventional stains, hematoxylin-eosin/phloxine (HE/P) under fluorescence and confocal microscopy presented a highly detailed observation of the elastic system in different organs and scenarios. This technique provides a better demarcation of the elastic fibers, favoring their description in relation to their deposition and aggregation in different organs. Also, fibrils with low aggregation or loss of this characteristic are observed in an optimal view in the skin, heart valves, and large-caliber blood vessels. Degradation, fragmentation, and rupture were also well described by the HE/P technique. Several organs, such as the mammary gland, prostate, skin, aorta, and lung, could be described with precision under this technique. In association with non-linear microscopy, the results of the research presented in this paper improved and detailed characteristics of precise pathogenesis. Thus, the HE/P technique presented an interesting efficiency to demonstrate alterations and structures in which the elastic system showed a relevant role, and when compared to other techniques it demonstrated a similar or better result. In addition, it is expected that future studies can reveal more information about the elastin and interactions with specific dyes, thus allowing a greater understanding of the great efficiency of this technique.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152209"},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuronal splicing regulator RNA binding protein, fox-1 homolog 3 (NeuN/RbFox3), is expressed in postmitotic neurons and distributed heterogeneously in the cell. During excitotoxicity events caused by the excess glutamate, several alterations that culminate in neuronal death have been described. However, NeuN/RbFox3 organization and distribution are still unknown. Therefore, our objective was to analyze the nucleocytoplasmic distribution and organization of NeuN/RbFox3 in hippocampal and cortical neurons using an excitotoxicity model with monosodium glutamate salt (MSG). We used neonatal Wistar rats administered subcutaneously with 4 MSG mg/kg during the postnatal day (PND) 1, 3, 5, and 7. The control group was rats without MSG administration. On 14 PND, the brain was removed, and coronal sections were used for immunodetection with the antibody NeuN, DAPI, and the propidium iodide staining for histological evaluation. The results indicate that in the control group, NeuN/RbFox3 was organized into macromolecular condensates inside and outside the nucleus, forming defined nuclear compartments. Additionally, NeuN/RbFox3 was distributed proximal to the nucleus in the cytoplasm. In contrast, in the group treated with MSG, the distribution was diffuse and dispersed in the nucleus and cytoplasm without the formation of compartments in the nucleus. Our findings, which highlight the significant impact of MSG administration in the neonatal period on the distribution and organization of NeuN/RbFox3 of neurons in the hippocampus and cerebral cortex, offer a new perspective to investigate MSG alterations in the developmental brain.
{"title":"Neuronal splicing regulator RBFOX3 (NeuN) distribution and organization are modified in response to monosodium glutamate in rat brain at postnatal day 14","authors":"Anaís Monzerrat García Juárez, Nidia Jannette Carrillo González, Tania Campos-Ordoñez, Yadira Gasca Martínez, Graciela Gudiño-Cabrera","doi":"10.1016/j.acthis.2024.152207","DOIUrl":"10.1016/j.acthis.2024.152207","url":null,"abstract":"<div><div>Neuronal splicing regulator RNA binding protein, fox-1 homolog 3 (NeuN/RbFox3), is expressed in postmitotic neurons and distributed heterogeneously in the cell. During excitotoxicity events caused by the excess glutamate, several alterations that culminate in neuronal death have been described. However, NeuN/RbFox3 organization and distribution are still unknown. Therefore, our objective was to analyze the nucleocytoplasmic distribution and organization of NeuN/RbFox3 in hippocampal and cortical neurons using an excitotoxicity model with monosodium glutamate salt (MSG). We used neonatal Wistar rats administered subcutaneously with 4 MSG mg/kg during the postnatal day (PND) 1, 3, 5, and 7. The control group was rats without MSG administration. On 14 PND, the brain was removed, and coronal sections were used for immunodetection with the antibody NeuN, DAPI, and the propidium iodide staining for histological evaluation. The results indicate that in the control group, NeuN/RbFox3 was organized into macromolecular condensates inside and outside the nucleus, forming defined nuclear compartments. Additionally, NeuN/RbFox3 was distributed proximal to the nucleus in the cytoplasm. In contrast, in the group treated with MSG, the distribution was diffuse and dispersed in the nucleus and cytoplasm without the formation of compartments in the nucleus. Our findings, which highlight the significant impact of MSG administration in the neonatal period on the distribution and organization of NeuN/RbFox3 of neurons in the hippocampus and cerebral cortex, offer a new perspective to investigate MSG alterations in the developmental brain.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152207"},"PeriodicalIF":2.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.acthis.2024.152204
Momoka Shobudani , Yuri Sakamaki , Ayumi Karasawa , Ryota Ojiro , Xinyu Zou , Qian Tang , Shunsuke Ozawa , Meilan Jin , Toshinori Yoshida , Makoto Shibutani
Fluoride affects neurodevelopment in children. In this study, we examined the effects of developmental exposure to sodium fluoride (NaF) on hippocampal neurogenesis in rats. Dams were given drinking water containing NaF at 0 (untreated controls), 30 or 100 ppm from gestational day 6 to day 21 post-delivery upon weaning, and offspring were reared until postnatal day (PND) 77. On PND 21, NaF at 100 ppm altered the numbers in subpopulations of granule cell lineages, including a decrease in type-3 neural progenitor cells (NPCs), as well as a compensatory increase in type-1 neural stem cells (NSCs) and type-2a NPCs. NaF exposure tended to increase GluR2+ mossy cells in the hilus of the dentate gyrus (DG) in a dose-dependent manner, suggesting that NaF exposure induces a compensatory neurogenic response. NaF also caused a dose-dependent increase in ARC+ granule cells, and it upregulated Ptgs2 in the DG at 100 ppm, suggesting that NaF exposure increases synaptic plasticity in granule cells. NaF at 100 ppm upregulated granule cell lineage marker genes (Nes, Eomes and Rbfox3) and an anti-apoptotic gene (Bcl2), suggesting ameliorating responses against the impaired neurogenesis during NaF exposure. Moreover, NaF at 100 ppm downregulated oxidative phosphorylation-related genes (Atp5f1b and Sdhd) and upregulated a glycolysis-related gene (Hk3), suggesting a metabolic shift in cells undergoing neurogenesis. By PND 77, the changes in granule cell lineages were no longer detected, and GABAergic interneuron marker genes (Calb2 and Reln) were upregulated, suggesting a persistent protective response in granule cell lineages. Together, these findings suggest that developmental NaF exposure causes transient disruption of hippocampal neurogenesis, which in turn induces a metabolic shift as a compensatory response.
{"title":"Metabolic shift as a compensatory response to impaired hippocampal neurogenesis after developmental exposure to sodium fluoride in rats","authors":"Momoka Shobudani , Yuri Sakamaki , Ayumi Karasawa , Ryota Ojiro , Xinyu Zou , Qian Tang , Shunsuke Ozawa , Meilan Jin , Toshinori Yoshida , Makoto Shibutani","doi":"10.1016/j.acthis.2024.152204","DOIUrl":"10.1016/j.acthis.2024.152204","url":null,"abstract":"<div><div>Fluoride affects neurodevelopment in children. In this study, we examined the effects of developmental exposure to sodium fluoride (NaF) on hippocampal neurogenesis in rats. Dams were given drinking water containing NaF at 0 (untreated controls), 30 or 100 ppm from gestational day 6 to day 21 post-delivery upon weaning, and offspring were reared until postnatal day (PND) 77. On PND 21, NaF at 100 ppm altered the numbers in subpopulations of granule cell lineages, including a decrease in type-3 neural progenitor cells (NPCs), as well as a compensatory increase in type-1 neural stem cells (NSCs) and type-2a NPCs. NaF exposure tended to increase GluR2<sup>+</sup> mossy cells in the hilus of the dentate gyrus (DG) in a dose-dependent manner, suggesting that NaF exposure induces a compensatory neurogenic response. NaF also caused a dose-dependent increase in ARC<sup>+</sup> granule cells, and it upregulated <em>Ptgs2</em> in the DG at 100 ppm, suggesting that NaF exposure increases synaptic plasticity in granule cells. NaF at 100 ppm upregulated granule cell lineage marker genes (<em>Nes</em>, <em>Eomes</em> and <em>Rbfox3</em>) and an anti-apoptotic gene (<em>Bcl2</em>), suggesting ameliorating responses against the impaired neurogenesis during NaF exposure. Moreover, NaF at 100 ppm downregulated oxidative phosphorylation-related genes (<em>Atp5f1b</em> and <em>Sdhd</em>) and upregulated a glycolysis-related gene (<em>Hk3</em>), suggesting a metabolic shift in cells undergoing neurogenesis. By PND 77, the changes in granule cell lineages were no longer detected, and GABAergic interneuron marker genes (<em>Calb2</em> and <em>Reln</em>) were upregulated, suggesting a persistent protective response in granule cell lineages. Together, these findings suggest that developmental NaF exposure causes transient disruption of hippocampal neurogenesis, which in turn induces a metabolic shift as a compensatory response.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152204"},"PeriodicalIF":2.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.acthis.2024.152206
Ivan Brdar , Tomislav Mašek , Anita Racetin , Marija Jurić , Katarina Vukojević , Ivana Bočina , Natalija Filipović
Diabetic nephropathy is the leading cause of end-stage kidney disease, and the association between impaired autophagy and kidney structure damage in diabetes is well known. Diets enriched with polyunsaturated fatty acids (PUFAs) have been the subject of numerous studies on preventing and treating various metabolic disorders. The results of these studies suggest that n-3 PUFA may have a renoprotective effect, reducing the structural damage to the kidneys associated with DM. We hypothesized that the activation of autophagy partly mediates the potential protective effect of n-3 PUFA on diabetic kidneys. Wistar rats were randomly divided into four groups according to the type of diet: control (C) and diabetic (STZ) groups received food including 0.5 % linseed oil and 2 % sunflower oil with an n-6/n-3 ratio of 7; the STZ+N6 group received a diet with 2.5 % sunflower oil with an n-6/n-3 ratio of 60; and the STZ+N3 group received a diet containing 2.5 % fish oil with an n-6/n-3 ratio of 1, with the addition of eicosapentaenoic acid (EPA) and 19 % docosahexaenoic acid (DHA). All rats, except for those in the C group, had diabetes induced by an intraperitoneal injection of streptozotocin. We conducted histological and immunohistochemical assessments to determine the effects of different n-6/n-3 PUFA dietary ratios on the expression levels of different autophagy markers in the kidney of the rats. The results indicate significant effects of n-3 and n-6 PUFA supplementation on the expression of different autophagy markers in the renal cortex of the diabetic rats. In particular, n-6 PUFA supplementation increased LC3B expression while simultaneously decreasing Rab7 expression; meanwhile, n-3 PUFA supplementation resulted in a decreased expression of LAMP2A and Rab7. Moreover, n-3 PUFA supplementation prevented an increase in BECL1 and p62, that was observed in kidneys from diabetic and diabetic n-3 supplemented animals. These results point to the complex interactions of fatty acids and autophagy during the development of diabetic kidney disease, which should be taken into account in future therapeutic approaches.
{"title":"Renal expression of autophagy markers in diabetic kidney of PUFA-supplemented rats","authors":"Ivan Brdar , Tomislav Mašek , Anita Racetin , Marija Jurić , Katarina Vukojević , Ivana Bočina , Natalija Filipović","doi":"10.1016/j.acthis.2024.152206","DOIUrl":"10.1016/j.acthis.2024.152206","url":null,"abstract":"<div><div>Diabetic nephropathy is the leading cause of end-stage kidney disease, and the association between impaired autophagy and kidney structure damage in diabetes is well known. Diets enriched with polyunsaturated fatty acids (PUFAs) have been the subject of numerous studies on preventing and treating various metabolic disorders. The results of these studies suggest that n-3 PUFA may have a renoprotective effect, reducing the structural damage to the kidneys associated with DM. We hypothesized that the activation of autophagy partly mediates the potential protective effect of n-3 PUFA on diabetic kidneys. Wistar rats were randomly divided into four groups according to the type of diet: control (C) and diabetic (STZ) groups received food including 0.5 % linseed oil and 2 % sunflower oil with an n-6/n-3 ratio of 7; the STZ+N6 group received a diet with 2.5 % sunflower oil with an n-6/n-3 ratio of 60; and the STZ+N3 group received a diet containing 2.5 % fish oil with an n-6/n-3 ratio of 1, with the addition of eicosapentaenoic acid (EPA) and 19 % docosahexaenoic acid (DHA). All rats, except for those in the C group, had diabetes induced by an intraperitoneal injection of streptozotocin. We conducted histological and immunohistochemical assessments to determine the effects of different n-6/n-3 PUFA dietary ratios on the expression levels of different autophagy markers in the kidney of the rats. The results indicate significant effects of n-3 and n-6 PUFA supplementation on the expression of different autophagy markers in the renal cortex of the diabetic rats. In particular, n-6 PUFA supplementation increased LC3B expression while simultaneously decreasing Rab7 expression; meanwhile, n-3 PUFA supplementation resulted in a decreased expression of LAMP2A and Rab7. Moreover, n-3 PUFA supplementation prevented an increase in BECL1 and p62, that was observed in kidneys from diabetic and diabetic n-3 supplemented animals. These results point to the complex interactions of fatty acids and autophagy during the development of diabetic kidney disease, which should be taken into account in future therapeutic approaches.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"126 8","pages":"Article 152206"},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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