{"title":"Starvation-induced sleep suppression requires the <i>Drosophila</i> brain nutrient sensor.","authors":"Yangkyun Oh, 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, JoonHu An, Subin Ha, 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}
Mari Kim, Gwang-Ic Son, Yun-Ho Cho, Gye-Hyeong Kim, Sung-Eun Yun, Young-Joon Kim, Jongkyeong Chung, Eunil Lee, Joong-Jean Park
{"title":"Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in <i>Drosophila</i>.","authors":"Mari Kim, Gwang-Ic Son, Yun-Ho Cho, Gye-Hyeong Kim, Sung-Eun Yun, Young-Joon Kim, Jongkyeong Chung, Eunil Lee, 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}
Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim
{"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, Ja Hoon Yoon, Yeo Jeong Han, 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}
Greg S B Suh, Kweon Yu, Young-Joon Kim, Yangkyun Oh, Joong-Jean Park
{"title":"History of <i>Drosophila</i> neurogenetic research in South Korea.","authors":"Greg S B Suh, Kweon Yu, Young-Joon Kim, Yangkyun Oh, 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, Greg S B Suh, 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}
Shinrye Lee, Myungjin Jo, Younghwi Kwon, Yu-Mi Jeon, Seyeon Kim, Kea Joo Lee, Hyung-Jun Kim
{"title":"PTK2 regulates tau-induced neurotoxicity via phosphorylation of p62 at Ser403.","authors":"Shinrye Lee, Myungjin Jo, Younghwi Kwon, Yu-Mi Jeon, Seyeon Kim, Kea Joo Lee, 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}
Jineun Kim, Dae-Gun Kim, Wongyo Jung, Greg S B Suh
{"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, Dae-Gun Kim, Wongyo Jung, 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}
{"title":"Inter-organ regulation by the brain in <i>Drosophila</i> development and physiology.","authors":"Sunggyu Yoon, Mingyu Shin, Jiwon Shim","doi":"10.1080/01677063.2022.2137162","DOIUrl":"https://doi.org/10.1080/01677063.2022.2137162","url":null,"abstract":"<p><p>The brain plays an essential role in regulating physiological homeostasis by communicating with other organs. Neuronal cells either directly innervate target tissues and transmit signals or secrete systemic factors into the hemolymph to regulate bodily functions, including physiology, development, metabolism, and immunity. In this review, we discuss the systemic functions of inter-organ communication mediated by the brain in four distinct categories: (1) nutrient sensing and feeding, (2) gastrointestinal activity and metabolism, (3) development and metamorphosis, and (4) immunity and hematopoiesis. First, we describe how chemosensory signals are sensed and transmitted to the brain in <i>Drosophila</i> and how the brain stimulates or modifies feeding behavior. Second, we summarize the brain-organ axis that regulates appetite activities and neuroendocrine pathways that maintain metabolic homeostasis. Third, we discuss how overall development in <i>Drosophila</i> is achieved by insulin and how it affects ecdysone signaling to initiate pupariation. Finally, we discuss how the central or peripheral nervous system controls hematopoiesis and innate immunity in <i>Drosophila</i> larvae. Given the functional parallels between <i>Drosophila</i> and humans, homologous pathways are likely to be conserved in human development and disease models, and the fly model system will continue to provide mechanistic insights into understanding complex interactions.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"57-69"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9776568","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":"Circadian gating of light-induced arousal in <i>Drosophila</i> sleep.","authors":"Hoyeon Lee, Chunghun Lim","doi":"10.1080/01677063.2022.2151596","DOIUrl":"https://doi.org/10.1080/01677063.2022.2151596","url":null,"abstract":"<p><p>Circadian rhythms and sleep homeostasis constitute the two-process model for daily sleep regulation. However, evidence for circadian control of sleep-wake cycles has been relatively short since clock-less animals often show sleep behaviors quantitatively comparable to wild-type. Here we examine <i>Drosophila</i> sleep behaviors under different light-dark regimes and demonstrate that circadian clocks gate light-induced arousal. Genetic excitation of tyrosine decarboxylase 2 (TDC2)-expressing neurons suppressed sleep more evidently at night, causing nocturnal activity. The arousal effects were likely mediated in part by glutamate transmission from the octopaminergic neurons and substantially masked by light. Application of T12 cycles (6-h light: 6-h dark) further showed that the light-sensitive effects of TDC2 neurons depended on the time of the day. In particular, light-sensing via visual input pathway led to strong sleep suppression at subjective night, and such an effect disappeared in clock-less mutants. Transgenic mapping revealed that light-induced arousal and free-running behavioral rhythms require distinct groups of circadian pacemaker neurons. These results provide convincing evidence that circadian control of sleep is mediated by the dedicated clock neurons for light-induced arousal.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"36-46"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9783262","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}