The Caenorhabditis elegans Choline Transporter CHO-1 Sustains Acetylcholine Synthesis and Motor Function in an Activity-Dependent Manner

Abstract The signaling pathway initiated by the TGF-β family member DBL-1 in Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of-function (lf) mutations in the dbl-1 gene cause a short, small body (Sma phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype). To understand the cellular mechanisms underlying these phenotypes, we have isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation. Two of these suppressors are mutations in the lon-3 gene, of which four additional alleles are known. We show that lon-3 encodes a collagen that is a component of the C. elegans cuticle. Genetic and reporter-gene expression analyses suggest that lon-3 is involved in determination of body shape and is post-transcriptionally regulated by the dbl-1 pathway. These results support the possibility that TGF-β signaling controls C. elegans body shape by regulating cuticle composition.

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Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations

Journal of Alzheimer s Disease ◽

10.3233/jad-201174 ◽

2021 ◽

pp. 1-16

Author(s):

Masaki Nakano ◽

Yachiyo Mitsuishi ◽

Lei Liu ◽

Naoki Watanabe ◽

Emi Hibino ◽

...

Keyword(s):

Neuronal Activity ◽

Epithelial Mesenchymal Transition ◽

Surrogate Marker ◽

Amyloid Β ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Extracellular Release ◽

Activity Dependent ◽

Aβ Production

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer’s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor. Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain. Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA. Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment. Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ.

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The defense response of Caenorhabditis elegans to Cutibacterium acnes SK137 via the TIR-1-p38 MAPK signaling pathway

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab218 ◽

2021 ◽

Author(s):

Ayano Tsuru ◽

Yumi Hamazaki ◽

Shuta Tomida ◽

Mohammad Shaokat Ali ◽

Eriko Kage-Nakadai

Keyword(s):

Caenorhabditis Elegans ◽

Signaling Pathway ◽

P38 Mapk ◽

Defense Response ◽

Mapk Pathway ◽

Defense Responses ◽

Mapk Signaling ◽

Dependent Manner ◽

Healthy Skin ◽

Cutibacterium Acnes

Abstract Cutibacterium acnes plays roles in both acne disease and healthy skin ecosystem. We observed that mutations in the tir-1/SARM1 and p38 MAPK cascade genes significantly shortened Caenorhabditis elegans lifespan upon Cutibacterium acnes SK137 infection. Antimicrobial molecules were induced by SK137 in a TIR-1-dependent manner. These results suggest that defense responses against SK137 involve the TIR-1-p38 MAPK pathway in Caenorhabditis elegans.

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Loss of miR-83 extends lifespan and affects target gene expression in an age-dependent manner in Caenorhabditis elegans

Journal of Genetics and Genomics ◽

10.1016/j.jgg.2018.11.003 ◽

2018 ◽

Vol 45 (12) ◽

pp. 651-662 ◽

Cited By ~ 5

Author(s):

Emmanuel Enoch Dzakah ◽

Ahmed Waqas ◽

Shuai Wei ◽

Bin Yu ◽

Xiaolin Wang ◽

...

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Target Gene ◽

Dependent Manner ◽

Target Gene Expression ◽

Age Dependent

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Neural and genetic degeneracy underlies Caenorhabditis elegans feeding behavior

Journal of Neurophysiology ◽

10.1152/jn.00150.2014 ◽

2014 ◽

Vol 112 (4) ◽

pp. 951-961 ◽

Cited By ~ 28

Author(s):

Nicholas F. Trojanowski ◽

Olivia Padovan-Merhar ◽

David M. Raizen ◽

Christopher Fang-Yen

Keyword(s):

Caenorhabditis Elegans ◽

Neural Circuit ◽

Dependent Manner ◽

State Dependent ◽

Excitatory Pathways ◽

Genetic Mechanisms ◽

Genetic Level ◽

Pharyngeal Pumping ◽

Robust Network

Degenerate networks, in which structurally distinct elements can perform the same function or yield the same output, are ubiquitous in biology. Degeneracy contributes to the robustness and adaptability of networks in varied environmental and evolutionary contexts. However, how degenerate neural networks regulate behavior in vivo is poorly understood, especially at the genetic level. Here, we identify degenerate neural and genetic mechanisms that underlie excitation of the pharynx (feeding organ) in the nematode Caenorhabditis elegans using cell-specific optogenetic excitation and inhibition. We show that the pharyngeal neurons MC, M2, M4, and I1 form multiple direct and indirect excitatory pathways in a robust network for control of pharyngeal pumping. I1 excites pumping via MC and M2 in a state-dependent manner. We identify nicotinic and muscarinic receptors through which the pharyngeal network regulates feeding rate. These results identify two different mechanisms by which degeneracy is manifest in a neural circuit in vivo.

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Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner

Allergology International ◽

10.2332/allergolint.13-oa-0621 ◽

2014 ◽

Vol 63 (2) ◽

pp. 219-226 ◽

Cited By ~ 12

Author(s):

Hideo Iida ◽

Toshiro Takai ◽

Yusuke Hirasawa ◽

Seiji Kamijo ◽

Sakiko Shimura ◽

...

Keyword(s):

Cysteine Protease ◽

Protease Activity ◽

Dependent Manner ◽

Cysteine Protease Activity ◽

Activity Dependent

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Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

Frontiers in Neuroscience ◽

10.3389/fnins.2021.768262 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xuankang Wang ◽

Zhihao Zhang ◽

Zhijie Zhu ◽

Zhuowen Liang ◽

Xiaoshuang Zuo ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Growth Factor ◽

Motor Function ◽

Function Analysis ◽

Reactive Astrocytes ◽

Male Rats ◽

Dependent Manner ◽

Astrocyte Activation ◽

Cord Injury

After spinal cord injury (SCI), reactive astrocytes can be classified into two distinctive phenotypes according to their different functions: neurotoxic (A1) astrocytes and neuroprotective (A2) astrocytes. Our previous studies proved that photobiomodulation (PBM) can promote motor function recovery and improve tissue repair after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM contributes to repair after SCI by regulating the activation of astrocytes. Male rats subjected to clip-compression SCI were treated with PBM for two consecutive weeks, and the results showed that recovery of motor function was improved, the lesion cavity size was reduced, and the number of neurons retained was increased. We determined the time course of A1/A2 astrocyte activation after SCI by RNA sequencing (RNA-Seq) and verified that PBM inhibited A1 astrocyte activation and promoted A2 astrocyte activation at 7 days postinjury (dpi) and 14 dpi. Subsequently, potential signaling pathways related to A1/A2 astrocyte activation were identified by GO function analysis and KEGG pathway analysis and then studied in animal experiments and preliminarily analyzed in cultured astrocytes. Next, we observed that the expression of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF-β) was upregulated by PBM and that both factors contributed to the transformation of A1/A2 astrocytes in a dose-dependent manner. Finally, we found that PBM reduced the neurotoxicity of A1 astrocytes to dorsal root ganglion (DRG) neurons. In conclusion, PBM can promote better recovery after SCI, which may be related to the transformation of A1/A2 reactive astrocytes.

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ZBP1 induces inflammatory signaling via RIPK3 and promotes SARS-CoV-2-induced cytokine expression

10.1101/2021.10.01.462460 ◽

2021 ◽

Author(s):

Ruoshi Peng ◽

Xuan Wang-Kan ◽

Manja Idorn ◽

Felix Y Zhou ◽

Susana L Orozco ◽

...

Keyword(s):

Cell Death ◽

Signaling Pathway ◽

Kinase Activity ◽

Caspase 8 ◽

Dependent Manner ◽

Innate Immune Responses ◽

Inflammatory Signaling ◽

Antiviral Responses ◽

Nucleic Acid Sensor ◽

Activity Dependent

AbstractCOVID-19 caused by the SARS-CoV-2 virus remains a threat to global health. The disease severity is mediated by cell death and inflammation, which regulate both the antiviral and the pathological innate immune responses. ZBP1, an interferon-induced cytosolic nucleic acid sensor, facilitates antiviral responses via RIPK3. Although ZBP1-mediated cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway that depends on ubiquitination and RIPK3’s scaffolding ability independently of cell death. In human cells, ZBP1 associates with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. RIPK1 and ZBP1 are ubiquitinated to promote TAK1- and IKK-mediated inflammatory signaling. Additionally, RIPK1 recruits the p43/41-caspase-8-p43-FLIP heterodimer to suppress RIPK3 kinase activity, which otherwise promotes inflammatory signaling in a kinase activity-dependent manner. Lastly, we show that ZBP1 contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK1-RIPK3-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspase-8. Our results suggest the ZBP1 pathway contributes to inflammation in response to SARS-CoV-2 infection.

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Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2113192118 ◽

2021 ◽

Vol 118 (52) ◽

pp. e2113192118

Author(s):

Alzahraa Amer ◽

Jianxun Xia ◽

Michael Smith ◽

John H. Martin

Keyword(s):

Spinal Cord ◽

Motor Cortex ◽

Corticospinal Tract ◽

Cervical Spinal Cord ◽

Long Term Potentiation ◽

Dependent Manner ◽

Term Potentiation ◽

Spinal Cord Segment ◽

Spinal Interneuron ◽

Activity Dependent

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST–spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

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Healthspan Improvements in Caenorhabditis elegans with Traditional Chinese Herbal Tea

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4057841 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Chunxiu Lin ◽

Xiaoying Zhang ◽

Chuting Zhuang ◽

Yugui Lin ◽

Yong Cao ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Disease Risk ◽

Underlying Mechanism ◽

Protective Mechanism ◽

Growth Factor Signaling ◽

Dependent Manner ◽

Herbal Tea ◽

Main Components ◽

Chinese Herbal Tea ◽

Late Stages

Searching for natural and safe herbal tea with health benefits has attracted more and more attention, which is of great significance for reducing disease risk. A Chinese traditional herbal tea (HT) is rich in active ingredients extracted from natural plants. Numerous pharmacological studies showed that HT had the potential to improve health, including antidepression and antioxidant effects. In this study, we proposed a strategy to explore the role and underlying mechanism of HT in improving healthspan of a Caenorhabditis elegans model. First, we found that HT significantly prolonged the lifespan without reducing fertility in worms. Second, stress resistance (oxidative stress and heat stress) was enhanced and Aβ- and polyQ-induced toxicity was relieved significantly by HT treatment. Both fat deposition and age pigment accumulation were found to be significantly reduced in HT-treated worms. The locomotion in mid-late stages was improved, indicating that behavioral mobility was also significantly enhanced. Furthermore, the main components of HT were eighteen polyphenols and two terpenoids. Finally, it was found that this protective mechanism was positively correlated with the insulin/insulin-like growth factor signaling- (IIS-) dependent manner, which went through promoting the nuclear localization of DAF-16 and its downstream SOD-3 expression. These results suggested that HT had an important role in improving health, which might serve as a promising healthy tea.

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