The effect of deletion of the nitric oxide synthase 1 gene (NOS1(-/-)) on radiosensitivity was determined. In vitro, long-term cultures of bone marrow stromal cells derived from NOS1(-/-) were more radioresistant than cells from C57BL/6NHsd (wild-type), NOS2(-/-) or NOS3(-/-) mice. Mice from each strain received 20 Gy thoracic irradiation or 9.5 Gy total-body irradiation (TBI), and NOS1(-/-) mice were more sensitive to both. To determine the etiology of radiosensitivity, studies of histopathology, lower esophageal contractility, gastrointestinal transit, blood counts, electrolytes and inflammatory markers were performed; no significant differences between irradiated NOS1(-/-) and control mice were found. Video camera surveillance revealed the cause of death in NOS1(-/-) mice to be grand mal seizures; control mice died with fatigue and listlessness associated with low blood counts after TBI. NOS1(-/-) mice were not sensitive to brain-only irradiation. MnSOD-PL therapy delivered to the esophagus of wild-type and NOS1(-/-) mice resulted in equivalent biochemical levels in both; however, in NOS1(-/-) mice, MnSOD-PL significantly increased survival after both thoracic and total-body irradiation. The mechanism of radiosensitivity of NOS1(-/-) mice and its reversal by MnSOD-PL may be related to the developmental esophageal enteric neuronal innervation abnormalities described in these mice.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946247 | PMC |
| http://dx.doi.org/10.1667/RR2019.1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
S-Nitrosylation of Dexras1 Controls Post-Stroke Recovery via Regulation of Neuronal Excitability and Dendritic Remodeling.
CNS Neurosci Ther
January 2025
Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Aims: Stroke is a major public health concern leading to high rates of death and disability worldwide, unfortunately with no effective treatment available for stroke recovery during the repair phase.
Methods: Photothrombotic stroke was induced in mice. Adeno-associated viruses (AAV) were microinjected into the peri-infarct cortex immediately after photothrombotic stroke.
A novel anti-epileptogenesis strategy of temporal lobe epilepsy based on nitric oxide donor.
EMBO Mol Med
December 2024
Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
The molecular mechanism underlying the role of hippocampal hilar interneuron degeneration in temporal lobe epilepsy (TLE) remains unclear. Especially, very few studies have focused on the role of neuronal nitric oxide synthase (nNOS, encoded by Nos1) containing hilar interneurons in TLE. In the present study, Nos1 conditional knockout mice were constructed, and we found that selective deletion of Nos1 in hilar interneurons rather than dentate granular cells (DGCs) triggered epileptogenesis.
View Article and Find Full Text PDFExercise training ameliorates carbon tetrachloride-induced liver fibrosis and anxiety-like behaviors.
Am J Physiol Gastrointest Liver Physiol
December 2024
Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan.
Article Synopsis
- Chronic liver diseases, including cirrhosis, are linked with mood disorders like anxiety, and this study investigates how regular exercise can impact these anxiety-like behaviors in mice with liver fibrosis.
- The research involved male C57/BL6 mice subjected to liver fibrosis through carbon tetrachloride (CCl) and tested the anxiolytic effects of voluntary exercise using an elevated plus maze for assessment.
- Findings indicate that exercise reduced anxiety-like behaviors and liver fibrosis markers, suggesting that exercise may offer therapeutic benefits by enhancing brain-derived neurotrophic factor (BDNF) levels and decreasing neuronal nitric oxide synthase (nNOS) activity, particularly in the hippocampus.
A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease.
Cell
October 2024
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:
Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp neurons, neurons expressing nitric oxide synthase 1 (Nos1 neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit.
View Article and Find Full Text PDFInterindividual Variation in Gut Nitrergic Neuron Density Is Regulated By GDNF Levels and ETV1.
Cell Mol Gastroenterol Hepatol
November 2024
Translational Neuroscience, Department of Pharmacology, Faculty of Medicine and Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden. Electronic address:
Background & Aims: The size and function of the enteric nervous system (ENS) can vary substantially between individuals. Because ENS function is involved in the etiology of a growing number of common human diseases, understanding mechanisms that regulate ENS variation is important.
Methods: We analyzed RNAseq data from 41 normal adult human colon biopsies and single-cell RNA-seq data from human and mouse developing gut.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!