Pub Date : 2023-09-01Epub Date: 2023-10-16DOI: 10.1080/01677063.2023.2259995
Zhiyong Li, Zhenggang Chen, Jun Peng
Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.
{"title":"Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification.","authors":"Zhiyong Li, Zhenggang Chen, Jun Peng","doi":"10.1080/01677063.2023.2259995","DOIUrl":"10.1080/01677063.2023.2259995","url":null,"abstract":"<p><p>Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2024-03-11DOI: 10.1080/01677063.2024.2319880
Robert Lalonde, Catherine Strazielle
DST is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive Dstdt (dystonia musculorum) spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to Dstdt mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous Dst mutations, targeted Dst knockout mice, DstTg4 transgenic mice carrying two deleted Dst exons, DstGt mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific Dst knockout mice. As a result of nerve damage, Dstdt mutants display dystonia and ataxia, as seen in several genetically modified models and their motor coordination deficits have been quantified along with the spontaneous Dst nonsense mutant, the conditional Schwann cell-specific Dst knockout, the conditional DstGt mutant, and the Dst-b isoform specific Dst mutant. Recent findings in humans have associated DST mutations of the Dst-b isoform with hereditary sensory and autonomic neuropathies type 6 (HSAN-VI). These data should further encourage the development of genetic techniques to treat or prevent ataxic and dystonic symptoms.
{"title":"The <i>DST</i> gene in neurobiology.","authors":"Robert Lalonde, Catherine Strazielle","doi":"10.1080/01677063.2024.2319880","DOIUrl":"10.1080/01677063.2024.2319880","url":null,"abstract":"<p><p><i>DST</i> is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive <i>Dst<sup>dt</sup></i> (<i>dystonia musculorum</i>) spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to <i>Dst<sup>dt</sup></i> mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous <i>Dst</i> mutations, targeted <i>Dst</i> knockout mice, <i>Dst</i>Tg4 transgenic mice carrying two deleted <i>Dst</i> exons, <i>Dst</i><sup>Gt</sup> mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific <i>Dst</i> knockout mice. As a result of nerve damage, <i>Dst<sup>dt</sup></i> mutants display dystonia and ataxia, as seen in several genetically modified models and their motor coordination deficits have been quantified along with the spontaneous <i>Dst</i> nonsense mutant, the conditional Schwann cell-specific <i>Dst</i> knockout, the conditional <i>Dst</i><sup>Gt</sup> mutant, and the Dst-b isoform specific <i>Dst</i> mutant. Recent findings in humans have associated <i>DST</i> mutations of the Dst-b isoform with hereditary sensory and autonomic neuropathies type 6 (HSAN-VI). These data should further encourage the development of genetic techniques to treat or prevent ataxic and dystonic symptoms.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-11-03DOI: 10.1080/01677063.2023.2270745
Qin Kang, Wen Chai, Jun Min, Xinhui Qu
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 NR4A1 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 NR4A1 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 NR4A1 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 NR4A1 promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.
{"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<sup>+</sup>) 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<sup>+</sup> treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP<sup>+</sup>-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP<sup>+</sup>-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP<sup>+</sup>-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with <i>NR4A1</i> promoter. In addition, in MPP<sup>+</sup>-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<sup>+</sup>-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP<sup>+</sup>-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<sup>+</sup>-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP<sup>+</sup>-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":null,"pages":null},"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}
Pub Date : 2023-09-01Epub Date: 2023-03-24DOI: 10.1080/01677063.2023.2187792
Stylianos Makrogkikas, Ruey-Kuang Cheng, Hao Lu, Sudipto Roy
Pkhd1l1 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 Pkhd1l1 specifically from hair cells, was associated with progressive hearing loss. In the zebrafish, there are two paralogous pkhd1l1 genes - pkhd1l1α and pkhd1l1β. 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 pkhd1l1 genes also regulate hearing; however, in contrast to Pkhd1l1 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 Pkhd1l1 in hearing and based on these findings from animal models, we postulate that PKHD1L1 could be a candidate gene for sensorineural hearing loss (SNHL) in humans.
{"title":"A conserved function of Pkhd1l1, a mammalian hair cell stereociliary coat protein, in regulating hearing in zebrafish.","authors":"Stylianos Makrogkikas, Ruey-Kuang Cheng, Hao Lu, 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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2023.2203489
Yangkyun Oh, Greg S B Suh
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 Drosophila 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.
{"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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2023.2210682
Geonil Kim, JoonHu An, Subin Ha, Anmo J Kim
Flying Drosophila 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 Drosophila 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.
{"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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2022.2144292
Mari Kim, Gwang-Ic Son, Yun-Ho Cho, Gye-Hyeong Kim, Sung-Eun Yun, Young-Joon Kim, Jongkyeong Chung, Eunil Lee, Joong-Jean Park
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 Drosophila. 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 Bcat 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 Bcat 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 Drosophila, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.
{"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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2022.2149747
Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim
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, GstO2 knockdown in Drosophila led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. Drosophila 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 GstO2 knockdown in vivo. Downregulation of GstO2 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 Drosophila.
{"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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2022.2115040
Greg S B Suh, Kweon Yu, Young-Joon Kim, Yangkyun Oh, Joong-Jean Park
Neurogenetic research using the Drosophila model has immensely expanded around the world. Likewise, scientists in South Korea have leveraged the advantages of Drosophila genetic tools to understand various neurobiological processes. In this special issue, we will overview the history of Drosophila neurogenetic research in South Korea that led to significant discoveries and notably implications. We will describe how Drosophila system was first introduced to elevate neural developmental studies in 1990s. Establishing Drosophila-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 Drosophila 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.
{"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":null,"pages":null},"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}
Pub Date : 2023-03-01DOI: 10.1080/01677063.2023.2216054
Jing W Wang, Greg S B Suh, Chun-Fang Wu
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.
{"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":null,"pages":null},"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}