Journal of neurogenetics最新文献

{"title":"Yin Yang 1 suppresses apoptosis and oxidative stress injury in SH-SY5Y cells by facilitating NR4A1 expression.","authors":"Qin Kang, Wen Chai, Jun Min, Xinhui Qu","doi":"10.1080/01677063.2023.2270745","DOIUrl":"10.1080/01677063.2023.2270745","url":null,"abstract":"<p><p>Oxidative stress plays a significant role in the development of Parkinson's disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP⁺) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the <i>NR4A1</i> promoter. MPP⁺ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP⁺-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP⁺-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with <i>NR4A1</i> promoter. In addition, in MPP⁺-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP⁺-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP⁺-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with <i>NR4A1</i> promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.HIGHLIGHTSNR4A1 and YY1 are decreased in MPP⁺-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP⁺-treated SH-SY5Y cells.YY1 binds with <i>NR4A1</i> promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"115-123"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434299","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}

{"title":"A conserved function of Pkhd1l1, a mammalian hair cell stereociliary coat protein, in regulating hearing in zebrafish.","authors":"Stylianos Makrogkikas,&nbsp;Ruey-Kuang Cheng,&nbsp;Hao Lu,&nbsp;Sudipto Roy","doi":"10.1080/01677063.2023.2187792","DOIUrl":"10.1080/01677063.2023.2187792","url":null,"abstract":"<p><p><i>Pkhd1l1</i> is predicted to encode a very large type-I transmembrane protein, but its function has largely remained obscure. Recently, it was shown that Pkhdl1l1 is a component of the coat that decorates stereocilia of outer hair cells in the mouse ear. Consistent with this localization, conditional deletion of <i>Pkhd1l1</i> specifically from hair cells, was associated with progressive hearing loss. In the zebrafish, there are two paralogous <i>pkhd1l1</i> genes - <i>pkhd1l1α</i> and <i>pkhd1l1β.</i> Using CRISPR-Cas9 mediated gene editing, we generated loss-of-function alleles for both and show that the double mutants exhibit nonsense-mediated-decay (NMD) of the RNAs. With behavioural assays, we demonstrate that zebrafish <i>pkhd1l1</i> genes also regulate hearing; however, in contrast to <i>Pkhd1l1</i> mutant mice, which develop progressive hearing loss, the double mutant zebrafish exhibited statistically significant hearing loss even from the larval stage. Our data highlight a conserved function of <i>Pkhd1l1</i> in hearing and based on these findings from animal models, we postulate that <i>PKHD1L1</i> could be a candidate gene for sensorineural hearing loss (SNHL) in humans.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":" ","pages":"85-92"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240088","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}

{"title":"Starvation-induced sleep suppression requires the <i>Drosophila</i> brain nutrient sensor.","authors":"Yangkyun Oh,&nbsp;Greg S B Suh","doi":"10.1080/01677063.2023.2203489","DOIUrl":"https://doi.org/10.1080/01677063.2023.2203489","url":null,"abstract":"<p><p>Animals increase their locomotion activity and reduce sleep duration under starved conditions. This suggests that sleep and metabolic status are closely interconnected. The nutrient and hunger sensors in the <i>Drosophila</i> brain, including diuretic hormone 44 (DH44)-, CN-, and cupcake-expressing neurons, detect circulating glucose levels in the internal milieu, regulate the insulin and glucagon secretion and promote food consumption. Food deprivation is known to reduce sleep duration, but a potential role mediated by the nutrient and hunger sensors in regulating sleep and locomotion activity remains unclear. Here, we show that DH44 neurons are involved in regulating starvation-induced sleep suppression, but CN neurons or cupcake neurons may not be involved in regulating starvation-induced sleep suppression or baseline sleep patterns. Inactivation of DH44 neurons resulted in normal daily sleep durations and patterns under fed conditions, whereas it ablated sleep reduction under starved conditions. Inactivation of CN neurons or cupcake neurons, which were proposed to be nutrient and hunger sensors in the fly brain, did not affect sleep patterns under both fed and starved conditions. We propose that the glucose-sensing DH44 neurons play an important role in mediating starvation-induced sleep reduction.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"70-77"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171511","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}

{"title":"A deep learning analysis of <i>Drosophila</i> body kinematics during magnetically tethered flight.","authors":"Geonil Kim,&nbsp;JoonHu An,&nbsp;Subin Ha,&nbsp;Anmo J Kim","doi":"10.1080/01677063.2023.2210682","DOIUrl":"https://doi.org/10.1080/01677063.2023.2210682","url":null,"abstract":"<p><p>Flying <i>Drosophila</i> rely on their vision to detect visual objects and adjust their flight course. Despite their robust fixation on a dark, vertical bar, our understanding of the underlying visuomotor neural circuits remains limited, in part due to difficulties in analyzing detailed body kinematics in a sensitive behavioral assay. In this study, we observed the body kinematics of flying <i>Drosophila</i> using a magnetically tethered flight assay, in which flies are free to rotate around their yaw axis, enabling naturalistic visual and proprioceptive feedback. Additionally, we used deep learning-based video analyses to characterize the kinematics of multiple body parts in flying animals. By applying this pipeline of behavioral experiments and analyses, we characterized the detailed body kinematics during rapid flight turns (or saccades) in two different visual conditions: spontaneous flight saccades under static screen and bar-fixating saccades while tracking a rotating bar. We found that both types of saccades involved movements of multiple body parts and that the overall dynamics were comparable. Our study highlights the importance of sensitive behavioral assays and analysis tools for characterizing complex visual behaviors.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"47-56"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9784307","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}

{"title":"Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in <i>Drosophila</i>.","authors":"Mari Kim,&nbsp;Gwang-Ic Son,&nbsp;Yun-Ho Cho,&nbsp;Gye-Hyeong Kim,&nbsp;Sung-Eun Yun,&nbsp;Young-Joon Kim,&nbsp;Jongkyeong Chung,&nbsp;Eunil Lee,&nbsp;Joong-Jean Park","doi":"10.1080/01677063.2022.2144292","DOIUrl":"https://doi.org/10.1080/01677063.2022.2144292","url":null,"abstract":"<p><p>The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male <i>Drosophila</i>. Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with the <i>Bcat</i> heterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when the <i>Bcat</i> expression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in <i>Drosophila</i>, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"25-35"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785853","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}

{"title":"Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a <i>drosophila</i> homolog of FUS, in the brain.","authors":"Sun Joo Cha,&nbsp;Ja Hoon Yoon,&nbsp;Yeo Jeong Han,&nbsp;Kiyoung Kim","doi":"10.1080/01677063.2022.2149747","DOIUrl":"https://doi.org/10.1080/01677063.2022.2149747","url":null,"abstract":"<p><p>Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, <i>GstO2</i> knockdown in <i>Drosophila</i> led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. <i>Drosophila</i> Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after <i>GstO2</i> knockdown <i>in vivo</i>. Downregulation of <i>GstO2</i> decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of <i>Drosophila</i>.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"20-24"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9788818","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}

{"title":"History of <i>Drosophila</i> neurogenetic research in South Korea.","authors":"Greg S B Suh,&nbsp;Kweon Yu,&nbsp;Young-Joon Kim,&nbsp;Yangkyun Oh,&nbsp;Joong-Jean Park","doi":"10.1080/01677063.2022.2115040","DOIUrl":"https://doi.org/10.1080/01677063.2022.2115040","url":null,"abstract":"<p><p>Neurogenetic research using the <i>Drosophila</i> model has immensely expanded around the world. Likewise, scientists in South Korea have leveraged the advantages of <i>Drosophila</i> genetic tools to understand various neurobiological processes. In this special issue, we will overview the history of <i>Drosophila</i> neurogenetic research in South Korea that led to significant discoveries and notably implications. We will describe how <i>Drosophila</i> system was first introduced to elevate neural developmental studies in 1990s. Establishing <i>Drosophila</i>-related resources has been a key venture, which led to the generation of over 100,000 mutant lines and the launch of the K-Gut initiative with Korea <i>Drosophila</i> Research Center (KDRC). These resources have supported the pioneer studies in modeling human disease and understanding genes and neural circuits that regulate animal behavior and physiology.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"3-9"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187434","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}

{"title":"Editorial/preface: Neurogenetics innovation in South Korea.","authors":"Jing W Wang,&nbsp;Greg S B Suh,&nbsp;Chun-Fang Wu","doi":"10.1080/01677063.2023.2216054","DOIUrl":"https://doi.org/10.1080/01677063.2023.2216054","url":null,"abstract":"Expanding the representation of research from countries beyond Europe and North America is a goal for the Journal of Neurogenetics. This special issue is designed to highlight the flourishing discipline of Drosophila neurogenetics in South Korea. The aim is to provide readers with a snapshot of the diverse research areas that are at the cutting edge of the field. Neurogenetics, the single-gene approach to study a wide range of neurobiological phenomena from the assembly of the nervous system, neurophysiology and circuit function to animal behaviors, has withstood early criticisms. Today, it stands as a fullyfledged and flourishing field. Early research efforts were focused on neural development and behavior, for which many genetic tools were produced. As these tools became more sophisticated, they were utilized to delve deeper and provide better mechanistic insights. The evolution of Drosophila neurogenetics in South Korea remarkably mirrors this progression. In the 1990s, a vast array of mutant lines was generated to study neural development, which enabled researchers to extend their investigations beyond their original questions. This expansion of research horizons fueled the creation of new and more advanced genetic reagents. This cycle of innovating with old tools, which eventually leads to the development of new ones, is a perfect encapsulation of the spirit of neurogenetics. This special issue is structured into four sections, beginning with the molecular mechanisms of neurodegeneration (Cha et al., 2022; Lee, Jo, et al., 2022), followed by the sensory modulation of sleep and arousal (Kim et al., 2022; Lee & Lim, 2022), then the use of machine learning to interrogate animal behaviors (Kim, An, et al., 2023; Kim, Kim, et al., 2023), and finally, nutrient sensors in feeding and non-feeding behaviors (Oh & Suh, 2022; Kim et al., 2023; Yoon et al., 2022). These studies offer exciting new findings as well as sketch out the future directions for the field in South Korea and around the world.","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"1-2"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173262","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}

{"title":"PTK2 regulates tau-induced neurotoxicity via phosphorylation of p62 at Ser403.","authors":"Shinrye Lee,&nbsp;Myungjin Jo,&nbsp;Younghwi Kwon,&nbsp;Yu-Mi Jeon,&nbsp;Seyeon Kim,&nbsp;Kea Joo Lee,&nbsp;Hyung-Jun Kim","doi":"10.1080/01677063.2022.2114471","DOIUrl":"https://doi.org/10.1080/01677063.2022.2114471","url":null,"abstract":"<p><p>Tau is a microtubule-associated protein that forms insoluble filaments that accumulate as neurofibrillary tangles in neurodegenerative diseases such as Alzheimer's disease and other related tauopathies. A relationship between abnormal Tau accumulation and ubiquitin-proteasome system impairment has been reported. However, the molecular mechanism linking Tau accumulation and ubiquitin proteasome system (UPS) dysfunction remains unclear. Here, we show that overexpression of wild-type or mutant (P301L) Tau increases the abundance of polyubiquitinated proteins and activates the autophagy-lysosome pathway in mammalian neuronal cells. Previous studies found that PTK2 inhibition mitigates toxicity induced by UPS impairment. Thus, we investigated whether PTK2 inhibition can attenuate Tau-induced UPS impairment and cell toxicity. We found that PTK2 inhibition significantly reduces Tau-induced death in mammalian neuronal cells. Moreover, overexpression of WT or mutant Tau increased the phosphorylation levels of PTK2 and p62. We also confirmed that PTK2 inhibition suppresses Tau-induced phosphorylation of PTK2 and p62. Furthermore, PTK2 inhibition significantly attenuated the climbing defect and shortened the lifespan in the <i>Drosophila</i> model of tauopathy. In addition, we observed that phosphorylation of p62 is markedly increased in Alzheimer's disease patients with tauopathies. Taken together, our results indicate that the UPS dysfunction induced by Tau accumulation might contribute directly to neurodegeneration in tauopathies and that PTK2 could be a promising therapeutic target for tauopathies.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"10-19"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9782169","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}

{"title":"Evaluation of mouse behavioral responses to nutritive versus nonnutritive sugar using a deep learning-based 3D real-time pose estimation system.","authors":"Jineun Kim,&nbsp;Dae-Gun Kim,&nbsp;Wongyo Jung,&nbsp;Greg S B Suh","doi":"10.1080/01677063.2023.2174982","DOIUrl":"https://doi.org/10.1080/01677063.2023.2174982","url":null,"abstract":"<p><p>Animals are able to detect the nutritional content of sugar independently of taste. When given a choice between nutritive sugar and nonnutritive sugar, animals develop a preference for nutritive sugar over nonnutritive sugar during a period of food deprivation (Buchanan <i>et al.</i>, 2022; Dus <i>et al.</i>, 2011; 2015; Tan <i>et al.</i>, 2020; Tellez <i>et al.</i>, 2016). To quantify behavioral features during an episode of licking nutritive versus nonnutritive sugar, we implemented a multi-vision, deep learning-based 3D pose estimation system, termed the AI Vision Analysis for Three-dimensional Action in Real-Time (AVATAR)(Kim <i>et al.</i>, 2022). Using this method, we found that mice exhibit significantly different approach behavioral responses toward nutritive sugar versus nonnutritive sugar even before licking a sugar solution. Notably, the behavioral sequences during the approach toward <i>nutritive</i> versus nonnutritive sugar became significantly different over time. These results suggest that the nutritional value of sugar not only promotes its consumption but also elicits distinct repertoires of feeding behavior in deprived mice.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"78-83"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9787480","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}