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Keywords = transcriptomic neuropeptides

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19 pages, 1835 KiB  
Article
Transcriptome Analysis Reveals Hyperglycemic Hormone and Excitatory Amino Acid Transporter 3 Are Involved in the Thermal Adaptation of Eriocheir sinensis
by Xi Li, Runlin Zhou, Ruiqi Zhang, Zhen He, Mingzhi Zhang, Ran Li, Tong Hao and Jinsheng Sun
Fishes 2025, 10(7), 361; https://doi.org/10.3390/fishes10070361 - 21 Jul 2025
Viewed by 267
Abstract
Temperature is one of the critical factors influencing the survival, growth, and reproduction of organisms. The molting and developmental mechanisms of crustaceans are highly sensitive to temperature, yet the regulatory mechanisms underlying their thermal adaptation remain unclear. In this work, transcriptome sequencing was [...] Read more.
Temperature is one of the critical factors influencing the survival, growth, and reproduction of organisms. The molting and developmental mechanisms of crustaceans are highly sensitive to temperature, yet the regulatory mechanisms underlying their thermal adaptation remain unclear. In this work, transcriptome sequencing was performed to analyze the gene expression profiles of Eriocheir sinensis under normal temperature (22 °C) and high-temperature (27 °C and 32 °C) conditions. A total of 377 differentially expressed genes (DEGs) were identified, including 149 up-regulated and 227 down-regulated genes. Through Gene Ontology (GO) enrichment analysis of these DEGs, 11 significantly temperature-regulated signaling pathways were identified, including the estrogen and androgen receptor signaling pathways, and two neurotransmission signaling pathways. These findings suggest that temperature may influence sex regulation in E. sinensis, while the dopamine receptor and neuropeptide signaling pathways may play a role in its thermal adaptation. Further validation via RT-qPCR of DEGs involved in neurotransmission signaling pathways revealed that crustacean hyperglycemic hormone (CHH) and excitatory amino acid transporter 3 (EAA3) genes are likely involved in the thermal adaptation of E. sinensis. In addition, the hemolymph glucose levels associated with the elevated temperatures were detected and consistent variations between glucose levels and CHH expressions were found. This indicates that the eyestalk CHH is strongly correlated with the hemolymph glucose levels and likely mediates the response to temperature changes by regulating blood glucose in E. sinensis. The results of this study not only provide key molecular targets for elucidating the mechanisms by which temperature affects molting and development in E. sinensis, but also establish a theoretical foundation for further research into thermal adaptation strategies in crustaceans. Full article
(This article belongs to the Section Aquatic Invertebrates)
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17 pages, 2226 KiB  
Article
Transcriptome-Wide Identification of Neuropeptides and Neuropeptide Receptors in the Twenty-Eight-Spotted Ladybird Henosepilachna vigintioctopunctata
by Quanxing Lei, Ziming Wang, Shuangyan Yao, Aili Lin, Yunhui Zhang, Chengxian Sun, Xiaoguang Liu, Mengfang Du, Xiaoming Liu and Shiheng An
Insects 2025, 16(6), 624; https://doi.org/10.3390/insects16060624 - 13 Jun 2025
Viewed by 691
Abstract
The ladybird beetle, Henosepilachna vigintioctopunctata, is an oligophagous pest with significant economic impact. This pest causes considerable economic damage on numerous Solanaceae crops. Neuropeptides, along with their designated receptors, play a pivotal role in regulating diverse biological processes in insects, presenting a [...] Read more.
The ladybird beetle, Henosepilachna vigintioctopunctata, is an oligophagous pest with significant economic impact. This pest causes considerable economic damage on numerous Solanaceae crops. Neuropeptides, along with their designated receptors, play a pivotal role in regulating diverse biological processes in insects, presenting a promising avenue for innovative pest management strategies. Herein, the transcriptome of the central nervous system (CNS) of H. vigintioctopunctata was sequenced. Overall, our analysis identified 58 neuropeptide precursor genes, from which 98 diverse mature peptides were predicted. Furthermore, 31 neuropeptide receptor genes belonging to three distinct classes were discovered, along with predictions for their potential ligands. Moreover, the expression patterns of these 58 neuropeptide genes across larval brain tissue, ventral nerve cord, and gut were evaluated using quantitative real-time PCR. Collectively, these findings will significantly contribute to future research focused on understanding the physiological functions and pharmacological characteristics of neuropeptides and their receptors in H. vigintioctopunctata. Ultimately, these insights may facilitate the development of targeted neuropeptide-based solutions for managing this pest affecting solanaceous plants. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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15 pages, 1608 KiB  
Article
Developmental Regulation of Corazonin, Eclosion Hormone, and Bursicon Messages and RNAi Suppression of Corazonin in Adult, Female American Dog Ticks, Dermacentor variabilis
by Anirudh Dhammi, Brooke Bissinger, Loganathan Ponnusamy, Daniel E. Sonenshine and R. Michael Roe
Insects 2025, 16(4), 343; https://doi.org/10.3390/insects16040343 - 25 Mar 2025
Viewed by 500
Abstract
The insect molting process is critical to growth and development and is regulated in part by the neuropeptides corazonin, eclosion hormone, and α and β bursicon. We found messages in a synganglion transcriptome from adult, female American dog ticks, Dermacentor variabilis (that do [...] Read more.
The insect molting process is critical to growth and development and is regulated in part by the neuropeptides corazonin, eclosion hormone, and α and β bursicon. We found messages in a synganglion transcriptome from adult, female American dog ticks, Dermacentor variabilis (that do not molt), with a high similarity to the larval insect neuropeptides that control molting. The phylogenetic analysis of the tick putative neuropeptides compared to other arthropods is discussed in detail. The relative gene expression of these peptides was determined by quantitative PCR during the following adult developmental stages: (i) virgin, unfed 0–24 h after entering the adult stage (non-host-seeking), (ii) host-seeking, unfed, and not mated (3 d after emergence), (iii) part-fed (unmated, attached to host; 1st and 3rd day after emergence), (iv) mated (females are part-fed; allowed to mate for ≤1 day, 7th day after emergence), (v) mated repletes (completion of blood feeding but still attached to host), and (vi) post-drop-off (from host) with egg laying starting within 1 d of detachment. Eclosion hormone transcript levels peaked at mating and at drop-off. Bursicon α levels were highest just after molting into adults, with a second smaller peak in replete females. Bursicon β levels were highest (32-fold) post-drop-off. Corazonin message levels peaked in part-feds and were much higher (40-fold) in repletes compared to 0–24 h after emergence. RNAi suppression of the corazonin message by injection in newly molted ticks reduced oviposition and the number of vitellogenic eggs in the ovaries at drop-off but had no apparent effect on host-seeking, partial feeding, mating, feeding to repletion, and drop-off. The possible roles of these transcripts in adult, female tick development are discussed. Full article
(This article belongs to the Section Insect Physiology, Reproduction and Development)
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15 pages, 1767 KiB  
Article
Key Neuropeptides Regulating Molting in Pacific White Shrimp (Penaeus vannamei): Insights from Transcriptomic Analysis
by Xianliang Li, Yunjiao Li, Zecheng Li and Hu Chen
Animals 2025, 15(4), 540; https://doi.org/10.3390/ani15040540 - 13 Feb 2025
Viewed by 867
Abstract
Molting is a vital physiological process essential for the growth and development of Penaeus vannamei, with significant implications for aquaculture productivity. This study aimed to identify neuropeptide-related genes involved in molting through transcriptomic analysis. RNA sequencing of pre-molt and post-molt samples revealed [...] Read more.
Molting is a vital physiological process essential for the growth and development of Penaeus vannamei, with significant implications for aquaculture productivity. This study aimed to identify neuropeptide-related genes involved in molting through transcriptomic analysis. RNA sequencing of pre-molt and post-molt samples revealed 1203 differentially expressed genes (DEGs). Functional enrichment analysis indicated that these genes play significant roles in cuticle formation and molting regulation. Among the DEGs, 243 were predicted to be neuropeptides based on the presence of signal peptides and the absence of transmembrane domains. Five key neuropeptide genes—PvCHH, PvMIH, PvEH I, PvCDA I, and PvCDA II—were identified as critical regulators of molting. Their role was further validated through RT-qPCR analysis, confirming their close association with the molting process. These genes were highlighted in this study as pivotal factors driving molting in P. vannamei. The neuropeptides identified in this research are anticipated to offer valuable insights into the regulation of molting. Additionally, their synthetic products hold promise for improving molting consistency in shrimp aquaculture. Full article
(This article belongs to the Section Animal Physiology)
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27 pages, 2257 KiB  
Article
Transcriptome and Neuroendocrinome Responses to Environmental Stress in the Model and Pest Insect Spodoptera frugiperda
by Wei Gong, Jan Lubawy, Paweł Marciniak, Guy Smagghe, Małgorzata Słocińska, Dongdong Liu, Tongxian Liu and Shunhua Gui
Int. J. Mol. Sci. 2025, 26(2), 691; https://doi.org/10.3390/ijms26020691 - 15 Jan 2025
Cited by 2 | Viewed by 1527
Abstract
The fall armyworm, Spodoptera frugiperda, is one of the most notorious pest insects, causing damage to more than 350 plant species, and is feared worldwide as an invasive pest species since it exhibits high adaptivity against environmental stress. Here, we therefore investigated [...] Read more.
The fall armyworm, Spodoptera frugiperda, is one of the most notorious pest insects, causing damage to more than 350 plant species, and is feared worldwide as an invasive pest species since it exhibits high adaptivity against environmental stress. Here, we therefore investigated its transcriptome responses to four different types of stresses, namely cold, heat, no water and no food. We used brain samples as our interest was in the neuroendocrine responses, while previous studies used whole bodies of larvae or moths. In general, the responses were complex and encompassed a vast array of neuropeptides (NPs) and biogenic amines (BAs). The NPs were mainly involved in ion homeostasis regulation (ITP and ITPL) and metabolic pathways (AKH, ILP), and this was accompanied by changes in BA (DA, OA) biosynthesis. Cold and no-water stress changed the NP gene expression with the same patterns of expression but clearly separated from each other, and the most divergent pattern of expression was shown after no-food stress. In conclusion, our data provide a foundation in an important model and pest insect with candidate NPs and BAs and other marker candidate genes in response to environmental stress, and also potential new targets to manage pest insects. Full article
(This article belongs to the Section Biochemistry)
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26 pages, 14325 KiB  
Article
Genome-Wide Identification and Expression of Neuropeptides and Their Expression Patterns After RNAi of CHH Genes in Pacific White Shrimp Litopenaeus vannamei
by Long Zhang, Lichao Sun, Guanghao Song, Beibei Wang, Yanting Cui, Fei Liu, Yuquan Li and Zhongkai Wang
Biology 2024, 13(12), 1038; https://doi.org/10.3390/biology13121038 - 11 Dec 2024
Cited by 1 | Viewed by 1303
Abstract
Neuropeptides are pivotal in regulating a broad spectrum of developmental, physiological, and behavioral processes throughout the life cycle of crustaceans. In this comprehensive study, we utilized a multiomics approach to characterize neuropeptide precursors and to assess the expression profiles of neuropeptide-encoding genes across [...] Read more.
Neuropeptides are pivotal in regulating a broad spectrum of developmental, physiological, and behavioral processes throughout the life cycle of crustaceans. In this comprehensive study, we utilized a multiomics approach to characterize neuropeptide precursors and to assess the expression profiles of neuropeptide-encoding genes across various tissues and developmental stages in the Pacific white shrimp, Litopenaeus vannamei. Additionally, we explored the differential expression of neuropeptide genes in the eyestalk before and after the RNA interference-mediated suppression of crustacean hyperglycemic hormone (CHH) and vitellogenesis-inhibiting hormone (VIH) gene expression. Our study identified a total of 125 neuropeptide-encoding genes in L. vannamei, with 54 of these genes previously uncharacterized in the genome. Notably, certain neuropeptide-encoding gene families showed significant expansion, as demonstrated by the discovery of 10 adipokinetic hormone/corazonin-like peptide (ACP) genes, 55 CHH superfamily genes, and 13 pigment-dispersing hormone (PDH) genes. Alternative splicing was also found to play a crucial role in generating functionally diverse neuropeptides; for example, the agatoxin and calcitonin genes undergo alternative splicing that leads to the production of three distinct agatoxin neuropeptides and two distinct calcitonin neuropeptides, respectively. Neuropeptide genes are predominantly expressed in neuroendocrine tissues, including the eyestalk, cerebral ganglia, thoracic ganglia, and ventral ganglia. During the embryonic development of L. vannamei, with the exception of the molt-inhibiting hormone (MIH) gene, all monitored genes display minimal expression from the zygote stage through to the larval in membrane (Lim) stage. In contrast, the majority of these genes exhibit a steady uptick in expression from the nauplius stage onwards, culminating in the post-larval stage. Furthermore, comparative transcriptomic analysis of the eyestalk revealed that the expression of the majority of neuropeptide genes was downregulated following the suppression of CHH and VIH gene expression. This downregulation was significantly associated with the enrichment of pathways related to amino acid metabolism and hormone synthesis. The findings of this study provide valuable insights for future research aimed at elucidating the role of neuropeptides in regulating physiological functions in L. vannamei, potentially leading to advancements in shrimp aquaculture practices. Full article
(This article belongs to the Special Issue Advances in Biological Research into Shrimps, Crabs and Lobsters)
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21 pages, 6147 KiB  
Article
Multifaceted Role of Specialized Neuropeptide-Intensive Neurons on the Selective Vulnerability to Alzheimer’s Disease in the Human Brain
by Manci Li, Nicole Flack and Peter A. Larsen
Biomolecules 2024, 14(12), 1518; https://doi.org/10.3390/biom14121518 - 27 Nov 2024
Viewed by 1168
Abstract
Regarding Alzheimer’s disease (AD), specific neuronal populations and brain regions exhibit selective vulnerability. Understanding the basis of this selective neuronal and regional vulnerability is essential to elucidate the molecular mechanisms underlying AD pathology. However, progress in this area is currently hindered by the [...] Read more.
Regarding Alzheimer’s disease (AD), specific neuronal populations and brain regions exhibit selective vulnerability. Understanding the basis of this selective neuronal and regional vulnerability is essential to elucidate the molecular mechanisms underlying AD pathology. However, progress in this area is currently hindered by the incomplete understanding of the intricate functional and spatial diversity of neuronal subtypes in the human brain. Previous studies have demonstrated that neuronal subpopulations with high neuropeptide (NP) co-expression are disproportionately absent in the entorhinal cortex of AD brains at the single-cell level, and there is a significant decline in hippocampal NP expression in naturally aging human brains. Given the role of NPs in neuroprotection and the maintenance of microenvironments, we hypothesize that neurons expressing higher levels of NPs (HNP neurons) possess unique functional characteristics that predispose them to cellular abnormalities, which can manifest as degeneration in AD with aging. To test this hypothesis, multiscale and spatiotemporal transcriptome data from ~1900 human brain samples were analyzed using publicly available datasets. The results indicate that HNP neurons experienced greater metabolic burden and were more prone to protein misfolding. The observed decrease in neuronal abundance during stages associated with a higher risk of AD, coupled with the age-related decline in the expression of AD-associated neuropeptides (ADNPs), provides temporal evidence supporting the role of NPs in the progression of AD. Additionally, the localization of ADNP-producing HNP neurons in AD-associated brain regions provides neuroanatomical support for the concept that cellular/neuronal composition is a key factor in regional AD vulnerability. This study offers novel insights into the molecular and cellular basis of selective neuronal and regional vulnerability to AD in human brains. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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26 pages, 18474 KiB  
Article
Neuropeptide FF Promotes Neuronal Survival and Enhances Synaptic Protein Expression Following Ischemic Injury
by In-Ae Choi, Ji Hee Yun, Jongmin Lee and Dong-Hee Choi
Int. J. Mol. Sci. 2024, 25(21), 11580; https://doi.org/10.3390/ijms252111580 - 28 Oct 2024
Cited by 1 | Viewed by 1231
Abstract
This study explores the neuroprotective effects of neuropeptide FF (NPFF, FLFQPQRFamide) in the context of ischemic injury. Based on transcriptomic analysis in stroke models treated with 5-Aza-dC and task-specific training, we identified significant gene expression changes, particularly involving NPFF. To further explore NPFF’s [...] Read more.
This study explores the neuroprotective effects of neuropeptide FF (NPFF, FLFQPQRFamide) in the context of ischemic injury. Based on transcriptomic analysis in stroke models treated with 5-Aza-dC and task-specific training, we identified significant gene expression changes, particularly involving NPFF. To further explore NPFF’s role in promoting neuronal recovery, recombinant NPFF protein (rNPFF) was used in primary mixed cortical cultures subjected to oxygen-glucose deprivation and reoxygenation. Our results demonstrated that rNPFF significantly reduced lactate dehydrogenase release, indicating decreased cellular damage. It also significantly increased the expression of TUJ1 and MAP2, markers of neuronal survival and dendritic integrity. Additionally, rNPFF significantly upregulated key synaptic proteins, including GAP43, PSD95, and synaptophysin, which are essential for synaptic repair and plasticity. Post-injury rNPFF treatment led to a significant upregulation of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, which play critical roles in neuronal survival, growth, and synaptic plasticity. Moreover, rNPFF activated the protein kinase Cε isoform, Sirtuin 1, and peroxisome proliferator-activated receptor gamma pathways, which are crucial for regulating cellular stress responses, synaptic plasticity, and energy homeostasis, further promoting neuronal survival and recovery. These findings suggest that rNPFF may play a pivotal role in enhancing neuronal survival and synaptic plasticity after ischemic injury, highlighting its potential as a therapeutic target for stroke recovery. Full article
(This article belongs to the Special Issue Current Insights on Neuroprotection)
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14 pages, 3217 KiB  
Article
Effects of Feeding Frequency on Liver Transcriptome: Unveiling Appetite-Regulating Peptides in Mexican Pike Silverside (Chirostoma estor)
by Mitzi Ernestina Juárez-Gutiérrez, Carlos Cristian Martínez-Chávez, Claudia Yaneth Godoy-Figueroa, Verónica Jiménez-Jacinto, María Gisela Ríos-Durán, Carlos Antonio Martínez-Palacios and Pamela Navarrete-Ramírez
Fishes 2024, 9(10), 393; https://doi.org/10.3390/fishes9100393 - 30 Sep 2024
Viewed by 1233
Abstract
The Mexican pike silverside (Chirostoma estor) is a zooplanktivorous, agastric short-intestined species, and it has been found that increased-frequency feeding (twelve feedings a day) improved feed efficiency and promoted growth by 70%. This work determined the effect of different juvenile feeding [...] Read more.
The Mexican pike silverside (Chirostoma estor) is a zooplanktivorous, agastric short-intestined species, and it has been found that increased-frequency feeding (twelve feedings a day) improved feed efficiency and promoted growth by 70%. This work determined the effect of different juvenile feeding frequencies upon the C. estor liver transcriptome. The level of the expression of appetite-regulating peptides was analyzed in silico to understand the mechanisms involved in appetite control in this species. Differential expression analysis showed that up-regulated genes between treatments were related to metabolism, digestive processes, immune system response, apoptosis, growth, and oxidative stress. This information explains the better performance of pike silverside fed 12 times daily. Appetite regulatory peptides were identified for the first time in the liver of C. estor in response to high feeding frequencies, contributing to the general knowledge of the roles of each family of neuropeptides in this agastric, short-intestined fish. The information presented here emphasizes the need to explore further the complex physiological processes involved in appetite regulation in C. estor. Additionally, it will serve as a basis for more specific targeted studies of appetite control to elucidate the mechanisms behind this process. Full article
(This article belongs to the Special Issue Advances in Fish Genome and Transcriptomes)
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12 pages, 2830 KiB  
Article
Unveiling the Impact of Rapeseed Meal on Feeding Behavior and Anorexigenic Endocrine in Litopenaeus vannamei
by Bo Zhou, Hongmei Ran, Qijun Zhang, Hu Chen, Fenglu Han, Chang Xu and Qun Zhao
Animals 2024, 14(4), 540; https://doi.org/10.3390/ani14040540 - 6 Feb 2024
Cited by 5 | Viewed by 1845
Abstract
Litopenaeus vannamei, with high plant protein acceptance and high global aquaculture production, is a potential species for rapeseed meal application. However, rapeseed meal has been associated with anorexia in fish, and whether the same occurs in L. vannamei remains unknown. This study [...] Read more.
Litopenaeus vannamei, with high plant protein acceptance and high global aquaculture production, is a potential species for rapeseed meal application. However, rapeseed meal has been associated with anorexia in fish, and whether the same occurs in L. vannamei remains unknown. This study demonstrated the effects of rapeseed meal on the feeding and anorexigenic endocrine of L. vannamei based on feeding behavior and transcriptomics. Soybean meal was replaced with fermented rapeseed meal (50%), and a significant increase in remaining diet and dietary discard was observed with a significant reduction in dietary visits. Transcriptome analysis revealed that the pathways involved in rapeseed meal-induced anorexia mainly included signal transduction, the digestive system, the sensory system, the endocrine system, phototransduction–fly, the thyroid hormone signaling pathway and pancreatic secretion. Moreover, this study further analyzed and identified seven neuropeptides involved in rapeseed meal-induced anorexia, and it explored the complex expression regulation strategies of these neuropeptides. In summary, this study confirmed through feeding behavior that rapeseed meal causes anorexia in L. vannamei, and it identified seven neuropeptides that were closely related to the anorexia process. Full article
(This article belongs to the Section Aquatic Animals)
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15 pages, 4097 KiB  
Article
Analysis of Transcriptomic Differences in the Ovaries of High- and Low-Laying Ducks
by Yuguang Chang, Rongbing Guo, Tao Zeng, Hanxue Sun, Yong Tian, Xue Han, Yongqing Cao, Ligen Xu, Mingcai Duan, Lizhi Lu and Li Chen
Genes 2024, 15(2), 181; https://doi.org/10.3390/genes15020181 - 29 Jan 2024
Cited by 3 | Viewed by 2312
Abstract
The egg-laying performance of Shan Ma ducks (Anas Platyrhynchos) is a crucial economic trait. Nevertheless, limited research has been conducted on the egg-laying performance of this species. We examined routine blood indicators and observed higher levels of metabolic and immune-related factors in the [...] Read more.
The egg-laying performance of Shan Ma ducks (Anas Platyrhynchos) is a crucial economic trait. Nevertheless, limited research has been conducted on the egg-laying performance of this species. We examined routine blood indicators and observed higher levels of metabolic and immune-related factors in the high-egg-production group compared with the low-egg-production group. Furthermore, we explored the ovarian transcriptome of both high- and low-egg-production groups of Shan Ma ducks using Illumina NovaSeq 6000 sequencing. A total of 1357 differentially expressed genes (DEGs) were identified, with 686 down-regulated and 671 up-regulated in the high-egg-production (HEP) ducks and low-egg-production (LEP) ducks. Several genes involved in the regulation of ovarian development, including neuropeptide Y (NPY), cell cycle protein-dependent kinase 1 (CDK1), and transcription factor 1 (E2F1), exhibited significant differential expressions at varying stages of egg production. Pathway functional analysis revealed that the DEGs were primarily associated with the steroid biosynthesis pathway, and the neuroactive ligand–receptor interaction pathway exhibited higher activity in the HEP group compared to the LEP group. This study offers valuable information about and novel insights into high egg production. Full article
(This article belongs to the Special Issue Poultry Genetics and Genomics)
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19 pages, 4030 KiB  
Article
Silica Nanoparticles Disclose a Detailed Neurodegeneration Profile throughout the Life Span of a Model Organism
by Annette Limke, Gereon Poschmann, Kai Stühler, Patrick Petzsch, Thorsten Wachtmeister and Anna von Mikecz
J. Xenobiot. 2024, 14(1), 135-153; https://doi.org/10.3390/jox14010008 - 12 Jan 2024
Cited by 1 | Viewed by 2262
Abstract
The incidence of age-related neurodegenerative diseases is rising globally. However, the temporal sequence of neurodegeneration throughout adult life is poorly understood. To identify the starting points and schedule of neurodegenerative events, serotonergic and dopaminergic neurons were monitored in the model organism C. elegans [...] Read more.
The incidence of age-related neurodegenerative diseases is rising globally. However, the temporal sequence of neurodegeneration throughout adult life is poorly understood. To identify the starting points and schedule of neurodegenerative events, serotonergic and dopaminergic neurons were monitored in the model organism C. elegans, which has a life span of 2–3 weeks. Neural morphology was examined from young to old nematodes that were exposed to silica nanoparticles. Young nematodes showed phenotypes such as dendritic beading of serotonergic and dopaminergic neurons that are normally not seen until late life. During aging, neurodegeneration spreads from specifically susceptible ADF and PDE neurons in young C. elegans to other more resilient neurons, such as dopaminergic CEP in middle-aged worms. Investigation of neurodegenerative hallmarks and animal behavior revealed a temporal correlation with the acceleration of neuromuscular defects, such as internal hatch in 2-day-old C. elegans. Transcriptomics and proteomics of young worms exposed to nano silica showed a change in gene expression concerning the gene ontology groups serotonergic and dopaminergic signaling as well as neuropeptide signaling. Consistent with this, reporter strains for nlp-3, nlp-14 and nlp-21 confirmed premature degeneration of the serotonergic neuron HSN and other neurons in young C. elegans. The results identify young nematodes as a vulnerable age group for nano silica-induced neural defects with a significantly reduced health span. Neurodegeneration of specific neurons impairs signaling by classical neurotransmitters as well as neuropeptides and compromises related neuromuscular behaviors in critical phases of life, such as the reproductive phase. Full article
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22 pages, 4845 KiB  
Article
ASCL1 Is Involved in the Pathogenesis of Schizophrenia by Regulation of Genes Related to Cell Proliferation, Neuronal Signature Formation, and Neuroplasticity
by Dmitrii A. Abashkin, Dmitry S. Karpov, Artemii O. Kurishev, Ekaterina V. Marilovtseva and Vera E. Golimbet
Int. J. Mol. Sci. 2023, 24(21), 15746; https://doi.org/10.3390/ijms242115746 - 30 Oct 2023
Cited by 5 | Viewed by 2651
Abstract
Schizophrenia (SZ) is a common psychiatric neurodevelopmental disorder with a complex genetic architecture. Genome-wide association studies indicate the involvement of several transcription factors, including ASCL1, in the pathogenesis of SZ. We aimed to identify ASCL1-dependent cellular and molecular mechanisms associated with SZ. We [...] Read more.
Schizophrenia (SZ) is a common psychiatric neurodevelopmental disorder with a complex genetic architecture. Genome-wide association studies indicate the involvement of several transcription factors, including ASCL1, in the pathogenesis of SZ. We aimed to identify ASCL1-dependent cellular and molecular mechanisms associated with SZ. We used Capture-C, CRISPR/Cas9 systems and RNA-seq analysis to confirm the involvement of ASCL1 in SZ-associated pathogenesis, establish a mutant SH-SY5Y line with a functional ASCL1 knockout (ASCL1-del) and elucidate differentially expressed genes that may underlie ASCL1-dependent pathogenic mechanisms. Capture-C confirmed the spatial interaction of the ASCL1 promoter with SZ-associated loci. Transcriptome analysis showed that ASCL1 regulation may be through a negative feedback mechanism. ASCL1 dysfunction affects the expression of genes associated with the pathogenesis of SZ, as well as bipolar and depressive disorders. Genes differentially expressed in ASCL1-del are involved in cell mitosis, neuronal projection, neuropeptide signaling, and the formation of intercellular contacts, including the synapse. After retinoic acid (RA)-induced differentiation, ASCL1 activity is restricted to a small subset of genes involved in neuroplasticity. These data suggest that ASCL1 dysfunction promotes SZ development predominantly before the onset of neuronal differentiation by slowing cell proliferation and impeding the formation of neuronal signatures. Full article
(This article belongs to the Special Issue CRISPR-Cas Systems and Genome Editing)
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43 pages, 4907 KiB  
Article
In Cerebellar Atrophy of 12-Month-Old ATM-Null Mice, Transcriptome Upregulations Concern Most Neurotransmission and Neuropeptide Pathways, While Downregulations Affect Prominently Itpr1, Usp2 and Non-Coding RNA
by Marina Reichlmeir, Júlia Canet-Pons, Gabriele Koepf, Wasifa Nurieva, Ruth Pia Duecker, Claudia Doering, Kathryn Abell, Jana Key, Matthew P. Stokes, Stefan Zielen, Ralf Schubert, Zoltán Ivics and Georg Auburger
Cells 2023, 12(19), 2399; https://doi.org/10.3390/cells12192399 - 3 Oct 2023
Cited by 4 | Viewed by 2896
Abstract
The autosomal recessive disorder Ataxia-Telangiectasia is caused by a dysfunction of the stress response protein, ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumour risk. However, it remains unclear [...] Read more.
The autosomal recessive disorder Ataxia-Telangiectasia is caused by a dysfunction of the stress response protein, ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumour risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits via bone-marrow transplantation, and that reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated that ATM depletion triggered upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently the neuropeptide machinery, e.g., Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM was localised only to cytoplasm, similar to the brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient/oxidative stress, but not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation. Full article
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15 pages, 1538 KiB  
Review
Fluorescent Molecules That Help Reveal Previously Unidentified Neural Connections in Adult, Neonatal and Peripubertal Mammals
by Enikő Vasziné Szabó, Katalin Köves and Ágnes Csáki
Int. J. Mol. Sci. 2023, 24(19), 14478; https://doi.org/10.3390/ijms241914478 - 23 Sep 2023
Viewed by 1480
Abstract
One hundred and twenty-five years ago there was a lively discussion between Hungarian and Spanish neuroscientists on the nature of neural connections. The question was whether the neurofibrils run from one neuron to the next and connect neurons as a continuous network or [...] Read more.
One hundred and twenty-five years ago there was a lively discussion between Hungarian and Spanish neuroscientists on the nature of neural connections. The question was whether the neurofibrils run from one neuron to the next and connect neurons as a continuous network or the fibrils form an internal skeleton in the neurons and do not leave the cell; however, there is close contact between the neurons. About 50 years later, the invention of the electron microscope solved the problem. Close contacts between individual neurons were identified and named as synapses. In the following years, the need arose to explore distant connections between neuronal structures. Tracing techniques entered neuroscience. There are three major groups of tracers: (A) non-transsynaptic tracers used to find direct connections between two neuronal structures; (B) tracers passing gap junctions; (C) transsynaptic tracers passing synapses that are suitable to explore multineuronal circuits. According to the direction of the transport mechanism, the tracer may be ante- or retrograde. In this review, we focus on the ever-increasing number of fluorescent tracers that we have also used in our studies. The advantage of the use of these molecules is that the fluorescence of the tracer can be seen in histological sections without any other processes. Genes encoding fluorescent molecules can be inserted in various neuropeptide or neurotransmitter expressing transcriptomes. This makes it possible to study the anatomy, development or functional relations of these neuronal networks in transgenic animals. Full article
(This article belongs to the Special Issue Research of Neuronal Cell in Nervous System Development and Disease)
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