Experimental and Molecular Medicine最新文献

{"title":"Author Correction: Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity","authors":"Ha Thu Nguyen, Andreas Wiederkehr, Claes B. Wollheim, Kyu-Sang Park","doi":"10.1038/s12276-024-01265-4","DOIUrl":"10.1038/s12276-024-01265-4","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment","authors":"Jared D. Rhodes, James R. Goldenring, Su-Hyung Lee","doi":"10.1038/s12276-024-01240-z","DOIUrl":"10.1038/s12276-024-01240-z","url":null,"abstract":"Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and the modulation of gastric carcinogenesis. This review summarizes how metaplasia (normal cells changing into different types) turns into dysplasia (abnormal cell growth) in the stomach due to injury and the role of stroma during the process. Led by Dr. James R. Goldenring, the team has discovered that the stomach develops metaplasia to heal damaged tissue and suggested several biomarkers to define the change. They recently found that certain types of metaplasia repopulate the stomach lining after damage and can progress into the next stage under the influence of the microenvironment. The current study provides insights into how the stromal components in the stomach contribute to carcinogenesis, focusing on fibroblast subpopulations. This could be important for future gastric cancer treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism","authors":"Su Hwan Park, Jin-Sung Ju, Hyunmin Woo, Hye Jin Yun, Su Bin Lee, Seok-Ho Kim, Balázs Győrffy, Eun-jeong Kim, Ho Kim, Hee Dong Han, Seong-il Eyun, Jong-Ho Lee, Yun-Yong Park","doi":"10.1038/s12276-024-01235-w","DOIUrl":"10.1038/s12276-024-01235-w","url":null,"abstract":"N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC. RNA methylation, a key process controlling gene activity, involves proteins like RNA-binding motif protein 15 (RBM15). Its role in breast cancer is unclear. Studies show RBM15 is highly active in a type of breast cancer called triple-negative and is linked to patient outcomes. It controls genes related to serine and glycine metabolism; substances that help cancer cells grow. The research demonstrates that RBM15 controls genes involved in the cancer metabolism of serine and glycine, two types of amino acids, which contributes to cancer cell proliferation. This suggests that targeting RBM15 can be new therapeutic approaches for triple-negative breast cancer patients. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma","authors":"Sanjib Chaudhary, Jawed Akhtar Siddiqui, Muthamil Iniyan Appadurai, Shailendra Kumar Maurya, Swathi P. Murakonda, Elizabeth Blowers, Ben J. Swanson, Mohd Wasim Nasser, Surinder K. Batra, Imayavaramban Lakshmanan, Apar Kishor Ganti","doi":"10.1038/s12276-024-01255-6","DOIUrl":"10.1038/s12276-024-01255-6","url":null,"abstract":"Non-small cell lung carcinoma (NSCLC) exhibits a heightened propensity for brain metastasis, posing a significant clinical challenge. Mucin 5ac (MUC5AC) plays a pivotal role in the development of lung adenocarcinoma (LUAD); however, its role in causing brain metastases remains unknown. In this study, we aimed to investigate the contribution of MUC5AC to brain metastasis in patients with LUAD utilizing various brain metastasis models. Our findings revealed a substantial increase in the MUC5AC level in LUAD brain metastases (LUAD-BrM) samples and brain-tropic cell lines compared to primary samples or parental control cell lines. Intriguingly, depletion of MUC5AC in brain-tropic cells led to significant reductions in intracranial metastasis and tumor growth, and improved survival following intracardiac injection, in contrast to the observations in the control groups. Proteomic analysis revealed that mechanistically, MUC5AC depletion resulted in decreased expression of metastasis-associated molecules. There were increases in epithelial-to-mesenchymal transition, tumor invasiveness, and metastasis phenotypes in tumors with high MUC5AC expression. Furthermore, immunoprecipitation and proteomic analysis revealed a novel interaction of MUC5AC with Annexin A2 (ANXA2), which activated downstream matrix metalloproteases and facilitated extracellular matrix degradation to promote metastasis. Disrupting MUC5AC-ANXA2 signaling with a peptide inhibitor effectively abrogated the metastatic process. Additionally, treatment of tumor cells with an astrocyte-conditioned medium or the chemokine CCL2 resulted in upregulation of MUC5AC expression and enhanced brain colonization. In summary, our study demonstrates that the MUC5AC/ANXA2 signaling axis promotes brain metastasis, suggesting a potential therapeutic paradigm for LUAD patients with high MUC5AC expression. Lung cancer frequently moves to the brain, but why is unclear. Scientists have found that a protein, MUC5AC, is crucial in this. The research, led by Sanjib Chaudhary and team, discovered that MUC5AC works with another protein, ANXA2, to help lung cancer cells move to the brain. They also found that astrocytes (a type of brain cell), release a substance that boosts the presence of MUC5AC in lung cancer cells. This research was a lab experiment using lung cancer cells and mice. They found that lowering MUC5AC in lung cancer cells greatly reduced their movement to the brain in mice. This suggests that focusing on MUC5AC could help stop lung cancer from moving to the brain. Future studies will need to confirm these results and look into possible treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locus of (IL-9) control: IL9 epigenetic regulation in cellular function and human disease","authors":"Aran Son, Ishita Baral, Guido H. Falduto, Daniella M. Schwartz","doi":"10.1038/s12276-024-01241-y","DOIUrl":"10.1038/s12276-024-01241-y","url":null,"abstract":"Interleukin-9 (IL-9) is a multifunctional cytokine with roles in a broad cross-section of human diseases. Like many cytokines, IL-9 is transcriptionally regulated by a group of noncoding regulatory elements (REs) surrounding the IL9 gene. These REs modulate IL-9 transcription by forming 3D loops that recruit transcriptional machinery. IL-9-promoting transcription factors (TFs) can bind REs to increase locus accessibility and permit chromatin looping, or they can be recruited to already accessible chromatin to promote transcription. Ample mechanistic and genome-wide association studies implicate this interplay between IL-9-modulating TFs and IL9 cis-REs in human physiology, homeostasis, and disease. Interleukin 9 (IL-9), a protein that helps the body’s immune system, has been researched for its role in various diseases. However, the mechanisms regulating IL-9 is production are not completely known. A team of researchers, led by A. Son and D.M. Schwartz, have reviewed how IL-9 production is controlled, focusing on specific elements within the IL9 gene and surrounding non-coding regulatory DNA. They reviewed existing studies, mainly in mice, and found several factors that bind to these elements and affect IL-9 production. They also discussed how IL9 epigenetics are connected to human diseases, finding links with allergies, autoimmune diseases, and cancer. These discoveries could aid in creating new treatments for these diseases. The researchers concluded that more studies are needed to fully understand how epigenetic regulation of IL-9 modulates disease. This could lead to new treatment strategies for various conditions. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances and challenges in modeling inherited peripheral neuropathies using iPSCs","authors":"Jonas Van Lent, Robert Prior, Gonzalo Pérez Siles, Anthony N. Cutrupi, Marina L. Kennerson, Tim Vangansewinkel, Esther Wolfs, Bipasha Mukherjee-Clavin, Zachary Nevin, Luke Judge, Bruce Conklin, Henna Tyynismaa, Alex J. Clark, David L. Bennett, Ludo Van Den Bosch, Mario Saporta, Vincent Timmerman","doi":"10.1038/s12276-024-01250-x","DOIUrl":"10.1038/s12276-024-01250-x","url":null,"abstract":"Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids. Inherited peripheral neuropathies are diseases that cause damage to the motor and sensory nervous system. Despite progress in understanding these diseases, effective treatments are still hard to find. This study looks at using induced pluripotent stem cells (iPSCs - cells that can turn into any type of cell in the body) to mimic the disease and find possible drug targets. The scientists used iPSCs to create different nerve cells and Schwann cells (cells that support nerve function). They studied these cells to see how the disease affects them. The study found that models made from iPSCs can accurately copy key aspects of the disease, providing valuable insights that add to findings from animal models. This research could lead to new treatments for inherited peripheral neuropathies. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of Tfh dynamics and the formation of immunological synapses","authors":"Ye-Ji Kim, Jinyong Choi, Youn Soo Choi","doi":"10.1038/s12276-024-01254-7","DOIUrl":"10.1038/s12276-024-01254-7","url":null,"abstract":"Inside germinal centers (GCs), antigen-specific B cells rely on precise interactions with immune cells and strategic localization between the dark and light zones to clonally expand, undergo affinity maturation, and differentiate into long-lived plasma cells or memory B cells. Follicular helper T (Tfh) cells, the key gatekeepers of GC-dependent humoral immunity, exhibit remarkable dynamic positioning within secondary lymphoid tissues and rely on intercellular interactions with antigen-presenting cells (APCs) during their differentiation and execution of B-cell-facilitating functions within GCs. In this review, we briefly cover the transcriptional regulation of Tfh cell differentiation and function and explore the molecular mechanisms governing Tfh cell motility, their interactions with B cells within GCs, and the impact of their dynamic behavior on humoral responses. This review focuses on T follicular helper (Tfh) cells—cells that are vital to antibody (Ab) production of the immune system. Led by Y.S. Choi, the team outlines how Tfh cells collaborate with B cells in our lymph nodes (small, bean-shaped glands throughout the body) to combat infections. The authors delve into genetic and molecular processes dictating Tfh cells’ actions. Key takeaways highlight the need for precise positioning and timing of Tfh cells with B cells, as well as the critical role of Tfh cell-B cell interaction intensity in B cell affinity maturation. The authors conclude the article by emphasizing the importance of gaining insights into these interactions to develop new therapeutic strategies for autoimmune diseases (conditions where the immune system mistakenly attacks the body), and to enhance vaccine responses. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated pre-miR-665/DLX3 m6A methylation facilitates the committed differentiation of stem cells from apical papilla","authors":"Tingjie Gu, Rong Guo, Yuxin Fang, Ya Xiao, Luyao Chen, Na Li, Xingyun Kelesy Ge, Yijia Shi, Jintao Wu, Ming Yan, Jinhua Yu, Zehan Li","doi":"10.1038/s12276-024-01245-8","DOIUrl":"10.1038/s12276-024-01245-8","url":null,"abstract":"Methyltransferase-like 3 (METTL3) is a crucial element of N6-methyladenosine (m6A) modifications and has been extensively studied for its involvement in diverse biological and pathological processes. In this study, we explored how METTL3 affects the differentiation of stem cells from the apical papilla (SCAPs) into odonto/osteoblastic lineages through gain- and loss-of-function experiments. The m6A modification levels were assessed using m6A dot blot and activity quantification experiments. In addition, we employed Me-RIP microarray experiments to identify specific targets modified by METTL3. Furthermore, we elucidated the molecular mechanism underlying METTL3 function through dual-luciferase reporter gene experiments and rescue experiments. Our findings indicated that METTL3+/− mice exhibited significant root dysplasia and increased bone loss. The m6A level and odonto/osteoblastic differentiation capacity were affected by the overexpression or inhibition of METTL3. This effect was attributed to the acceleration of pre-miR-665 degradation by METTL3-mediated m6A methylation in cooperation with the “reader” protein YTHDF2. Additionally, the targeting of distal-less homeobox 3 (DLX3) by miR-665 and the potential direct regulation of DLX3 expression by METTL3, mediated by the “reader” protein YTHDF1, were demonstrated. Overall, the METTL3/pre-miR-665/DLX3 pathway might provide a new target for SCAP-based tooth root/maxillofacial bone tissue regeneration. Dentition defects, or missing teeth, can cause long-term health issues and are typically treated with implant denture restoration, a method that often has complications. Recent studies suggest using dental stem cells for treatment. A study by Nanjing Medical University investigated the role of a molecule, METTL3, in the development of stem cells from the apical papilla (SCAPs), a type of dental stem cell. They discovered that METTL3 helps SCAPs develop into odonto/osteogenic cells, important for tooth and bone growth. This implies that METTL3 could enhance treatments for missing teeth. The study also found a regulatory network involving METTL3 and other molecules, which could be significant in future research. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion","authors":"Suji Kim, Sungbo Shim, Jisoo Kwon, Sungwoo Ryoo, Junyoung Byeon, Jungwoo Hong, Jeong-Hyung Lee, Young-Guen Kwon, Ji-Yoon Kim, Young-Myeong Kim","doi":"10.1038/s12276-024-01237-8","DOIUrl":"10.1038/s12276-024-01237-8","url":null,"abstract":"Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction. Synthetic miR-214-3p administration to pregnant mice decreased PlGF and eNOS expression, resulting in preeclampsia-like symptoms, including hypertension, proteinuria, and fetal growth restriction. Conversely, miR-214-3p deletion maintained the PlGF and eNOS levels in hypoxic pregnant mice, alleviating preeclampsia-like symptoms and signs. These findings provide new insights into the role of HIF-1/Twist1- and NF-κB-responsive miR-214-3p-dependent PlGF and eNOS downregulation in the pathogenesis of preeclampsia and establish miR-214-3p as a therapeutic or preventive target for preeclampsia and its complications. This research investigates how a molecule, miR-214-3p, impacts the occurrence of preeclampsia - a pregnancy issue marked by high blood pressure and organ damage. Scientists discovered that miR-214-3p produced more when oxygen levels are low, suppresses two other molecules, PlGF and eNOS, essential for a healthy pregnancy. In mouse experiments, artificially increasing miR-214-3p led to preeclampsia-like symptoms, while mice without miR-214-3p alleviated these symptoms in low oxygen. This suggests miR-214-3p could be a focus for preeclampsia prevention or treatment. Further studies are required to confirm this. “This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.”","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway","authors":"Kyeong-No Yoon, Sun Yong Kim, Jungeun Ji, Yidan Cui, Qing‐Ling Quan, Gunhyuk Park, Jang-Hee Oh, Ji Su Lee, Joon-Yong An, Jin Ho Chung, Yong-Seok Lee, Dong Hun Lee","doi":"10.1038/s12276-024-01242-x","DOIUrl":"10.1038/s12276-024-01242-x","url":null,"abstract":"The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure. Exposure to ultraviolet radiation, which is a harmful type of light from the sun, can cause skin inflammation and other health problems. This study looked at how UV radiation affects the brain, specifically focusing on dopamine, a chemical in the brain that helps control movement and emotional responses. The researchers did experiments on mice, exposing them to UV radiation and observing changes in their behavior and brain function. They found that UV radiation increased dopamine levels in the skin, adrenal glands, and brain. This increase was linked to memory loss and changes in behavior. The researchers concluded that UV radiation can affect brain function and behavior by changing dopamine levels. This study shows the importance of protecting against UV radiation and suggests that targeting dopamine receptors could help reduce the negative brain effects of UV exposure. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}