Summary Public health studies indicate that artificial light is a high-risk factor for metabolic disorders . However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus , and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism , which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.
Purpose Ochratoxin A (OTA) contamination of food and feed is a serious problem worldwide. OTA is considered a carcinogen and immunotoxic, nephrotoxic, and neurotoxic mycotoxin. The present study aims to determine the toxic effects of OTA on retinal ganglion cells (RGCs) and assess the resulting impairment of retinal function in mice. Methods RGC-5 cells were exposed to OTA (100 and 200 μg/L) for 3 days, and the mice were fed OTA-contain (100 and 200 μg/kg) diets for 4 weeks. Antioxidant indices were detected by spectrophotometer. The apoptosis of RGC-5 cells was determined by flow cytometry. Mitochondrial morphology and mitochondrial membrane potential were detected by immunofluorescence. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Results The oxidative-antioxidant balance suggested that OTA-induced severe oxidative stress, including increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the OTA-exposed RGC-5 cells, and the reduced activity of superoxide dismutase (SOD) and glutathione-S-transferase (GST) in the OTA exposed group. Furthermore, OTA exposure led to remarkable apoptosis in RGC-5 cells. The mitochondrial detection showed that OTA caused significant mitochondrial membrane potential reduction and mitochondrial fragmentation, which may be the cause of apoptosis of RGC-5 cells. Additionally, in vivo experiments demonstrated that OTA resulted in significant death of RGCs and subsequent retinal dysfunction in mice. Conclusion Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and RGCs death in mice.
Yang Hongbin,Liu Chang,Jiang Jie,Wang Yuena,Zhang Xiaoyu
This study was aimed to evaluate the effects of celastrol, a natural compound with multiple bioactivities, on multiple sclerosis and optic neuritis (ON) in rat experimental autoimmune encephalomyelitis (EAE). EAE was induced in Sprague Dawley rats using myelin basic protein, and the animals received daily intraperitoneal injections of celastrol or vehicle for 13 days. The EAE rats showed abnormal neurobehavior and inflammatory infiltration and demyelination in the spinal cord. Significantly upregulated mRNA expression of pro-inflammatory cytokines interferon-γ and interleukin-17 and downregulated anti-inflammatory cytokines interleukin-4 were found in the spinal cord of EAE rats. In the study of ON, severely inflammatory responses like in the spinal cord were also seen in the optic nerve, as well as obvious microgliosis. Furthermore, activation of nuclear factor kappa-B and upregulated inducible nitric oxide synthase was observed in the optic nerve. In addition, apoptosis of retinal ganglion cells and dysregulation of apoptotic-associated proteins in the optic nerve were found in EAE rats. Treatment of celastrol potently restored these changes. In most of the indexes, the effects of high dose of celastrol were better than the low dose. Our data conclude that administration of celastrol attenuates multiple sclerosis and ON in EAE via anti-inflammatory and anti-apoptotic effects. These findings provide new pre-clinical evidence for the use of celastrol in treatment of multiple sclerosis.
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