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Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.
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http://dx.doi.org/10.5625/lar.2018.34.4.317 | DOI Listing |
Nature
August 2025
Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
The poly(ADP-ribose) polymerase inhibitor (PARPi) class of drugs represents a remarkable advance in the treatment of patients with homologous recombination-deficient tumours, but resistance remains a challenge. Although most research has focused on the downstream consequences of PARPi exposure to tackle resistance, the immediate effect of PARP inhibition on the chromatin environment and its contribution to PARPi toxicity remains elusive. Here we show that PARP inhibition induces histone release from the chromatin.
View Article and Find Full Text PDFAtaxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. In this study, we explore the combination of the ATR inhibitor, ceralasertib, and palliative radiotherapy, with primary endpoint the identification of maximum tolerated dose, and secondary endpoints the determination of adverse event causality, pharmacokinetics (PK) and anti-tumor activity. Twenty-seven patients were dosed in escalating dose cohorts from 20 to 80 mg twice daily (BD) with concomitant radiation, 20 Gy in 10 fractions or 30 Gy in 15 fractions.
View Article and Find Full Text PDFNat Commun
July 2025
The ERC (Epi)Genetic Vulnerabilities in Solid Tumors and Sarcoma Laboratory, Inserm Unit UMR981, Gustave Roussy, Villejuif, France.
ADAR1 is an RNA editing enzyme which prevents autoimmunity by blocking interferon responses triggered by cytosolic RNA sensors, and is a potential target in immuno-oncology. However, predictive biomarkers for ADAR1 inhibition are lacking. Using multiple in vitro and in vivo systems, we show that BRCA1/2 and ADAR1 are synthetically lethal, and that ADAR1 activity is upregulated in BRCA1/2-mutant cancers.
View Article and Find Full Text PDFNPJ Breast Cancer
July 2025
University of Edinburgh Cancer Center, Western General Hospital, EDINBURGH United Kingdom, Edinburgh, UK.
This manuscript critically examines the challenges associated with the design and conduct of academic global breast cancer trials outside the influence of pharmaceutical companies, leveraging insights from the Breast International Group (BIG). In the past 4 decades significant declines in breast cancer mortality have occurred, partly related to industry-academic clinical and translational partnerships with long term study follow up. However, in the past decade these partnerships have largely uncoupled.
View Article and Find Full Text PDFEnviron Res
July 2025
Digital Omics Research Center, Korea Basic Science Institute, Cheongju, 28119, South Korea; Division of Bio-Analytical Science, University of Science and Technology, Daejeon, 34113, South Korea; Department of Plant Science and Technology, Chung-Ang University, Anseong, 17546, South Korea. Electronic
Arctic warming is accelerating at a rate approximately four times faster than the global average, exerting profound effects on soil organic matter and microbial activity, particularly in permafrost regions rich in soil carbon stocks. This study investigates the molecular composition of water-extractable organic matter (WEOM) in response to a 7-year period of warming via open-top chambers across different soil layers in a dry Arctic tundra ecosystem. We focused on elucidating the depth-dependent responses of WEOM to warming, emphasizing compositional shifts and proportional changes in WEOM constituents using ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS).
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