scholarly journals Neuronal Excitatory State Is Linked to Stress Resilience

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 372-372
Author(s):  
Bruce Yankner ◽  
Joseph Zullo
Keyword(s):  
Stress Response ◽  
Human Brain ◽  
Neuronal Excitability ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Response Factors ◽  
C Elegans ◽  
Neuronal Excitation ◽  
Excitatory State ◽  
Human Stress

Abstract The aging human brain is a study in both the importance and limitations of human stress response factors. Individual neurons can maintain functionality for 80 or more years, testifying to the potency of their stress response pathways. However, failure of these pathways during aging drastically increases the risk of neurodegenerative diseases. The transcriptional repressor REST is induced in the brains of long-lived humans but is lost in neurodegenerative disease. Here, we explore one modality of REST’s protective effects: regulation of neuronal excitability. We show that excitatory capacity and stress response are inversely correlated in the human brain. We find that REST and its C. elegans orthologs repress neuronal excitation in response to stressful conditions. Further, exogenously suppressing neuronal excitation restores stress resistance to REST-deficient animals, while enhancing stress response in wildtype ones. Thus, regulation of neuronal activity is an important aspect of neuronal stress response and a potential therapeutic modality.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinyoung Kim ◽  
Kihyoun Park ◽  
Min Jung Kim ◽  
Hyejin Lim ◽  
Kook Hwan Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid ◽  
Amyloid Accumulation ◽  
Human Diabetes

AbstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.

Clade III cytokinin response factors share common roles in response to oxidative stress responses linked to cytokinin synthesis

2021 ◽  
Vol 72 (8) ◽  
pp. 3294-3306
Author(s):  
Ariel M Hughes ◽  
H Tucker Hallmark ◽  
Lenka Plačková ◽  
Ondrej Novák ◽  
Aaron M Rashotte
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Stress Responses ◽  
Oxidative Stress Response ◽  
Response Factors ◽  
Ontology Term ◽  
Regulated Expression ◽  
Cytokinin Response ◽  
Oxidative Stress Responses

Abstract Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.

scholarly journals C. elegans discriminates colors to guide foraging

Science ◽  
2021 ◽  
Vol 371 (6533) ◽  
pp. 1059-1063 ◽  
Author(s):  
D. Dipon Ghosh ◽  
Dongyeop Lee ◽  
Xin Jin ◽  
H. Robert Horvitz ◽  
Michael N. Nitabach
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Color Discrimination ◽  
Cellular Stress Response ◽  
Blue Pigment ◽  
Natural Environments ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Foraging Decisions ◽  
Light Guides

Color detection is used by animals of diverse phyla to navigate colorful natural environments and is thought to require evolutionarily conserved opsin photoreceptor genes. We report that Caenorhabditis elegans roundworms can discriminate between colors despite the fact that they lack eyes and opsins. Specifically, we found that white light guides C. elegans foraging decisions away from a blue-pigment toxin secreted by harmful bacteria. These foraging decisions are guided by specific blue-to-amber ratios of light. The color specificity of color-dependent foraging varies notably among wild C. elegans strains, which indicates that color discrimination is ecologically important. We identified two evolutionarily conserved cellular stress response genes required for opsin-independent, color-dependent foraging by C. elegans, and we speculate that cellular stress response pathways can mediate spectral discrimination by photosensitive cells and organisms—even by those lacking opsins.

scholarly journals Gene expression profiling in peripheral blood leukocytes as a new approach for assessment of human stress response

2005 ◽  
Vol 52 (3,4) ◽  
pp. 137-144 ◽  
Author(s):  
Kazuhito Rokutan ◽  
Kyoko Morita ◽  
Kiyoshi Masuda ◽  
Kumiko Tominaga ◽  
Michiyo Shikishima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Gene Expression Profiling ◽  
Peripheral Blood ◽  
Expression Profiling ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
New Approach ◽  
Human Stress

scholarly journals Edible Flowers of Tagetes erecta L. as Functional Ingredients: Phenolic Composition, Antioxidant and Protective Effects on Caenorhabditis elegans

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 2002 ◽  
Author(s):  
Cristina Moliner ◽  
Lillian Barros ◽  
Maria Dias ◽  
Víctor López ◽  
Elisa Langa ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
In Vivo Model ◽  
Tagetes Erecta ◽  
Protective Effects ◽  
Phenolic Composition ◽  
C Elegans ◽  
Amyloid Toxicity ◽  
Phenolic Profiles ◽  
Tagetes Erecta L

Tagetes erecta L. has long been consumed for culinary and medicinal purposes in different countries. The aim of this study was to explore the potential benefits from two cultivars of T. erecta related to its polyphenolic profile as well as antioxidant and anti-aging properties. The phenolic composition was analyzed by LC-DAD-ESI/MSn. Folin-Ciocalteu, DPPH·, and FRAP assays were performed in order to evaluate reducing antiradical properties. The neuroprotective potential was evaluated using the enzymes acetylcholinesterase and monoamine oxidase. Caenorhabditis elegans was used as an in vivo model to assess extract toxicity, antioxidant activity, delayed aging, and reduced β-amyloid toxicity. Both extracts showed similar phenolic profiles and bioactivities. The main polyphenols found were laricitin and its glycosides. No acute toxicity was detected for extracts in the C. elegans model. T. erecta flower extracts showed promising antioxidant and neuroprotective properties in the different tested models. Hence, these results may add some information supporting the possibilities of using these plants as functional foods and/or as nutraceutical ingredients.

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