Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. METHODS: In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation. RESULTS: Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. CONCLUSION: Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.

Age-related hearing loss was accelerated by apoptosis of spiral ganglion and stria vascularis cells in ApoE KO mice with hyperglycemia and hyperlipidemia.

Age-related hearing loss (ARHL) is associated with diabetes and/or dyslipidemia in humans. However, the detailed mechanism for the development of ARHL by diabetes and/or dyslipidemia has not been elucidated. In this study, we investigated the etiology of ARHL in apolipoprotein E (ApoE)-deficient mice with diabetes and dyslipidemia. The atherosclerotic CD-STZ (mice fed with a control diet and received an STZ injection), WD-con (mice fed with a western diet), and WD-STZ (mice fed with a western diet and received an STZ injection) mice showed a 2.4-, 4.9-, and 6.8-fold larger area, respectively, occupied by lesions throughout the aorta compared with the CD-con mice. A significantly larger area under the curve (AUC) was observed in the STZ-treated groups than in the non-treated groups based on the oral glucose tolerance test (OGTT). At 20 weeks of age, HbA1c levels were significantly higher in the CD-STZ and WD-STZ mice than in the CD-con and WD-con mice. In all the groups, the auditory brainstem response (ABR) thresholds of the 16-week-old mice were significantly higher compared with those of the 8-week-old mice. In particular, in the WD-STZ mice, the ABR thresholds of the left and right ears reached the maximum decibel peak equivalent sound pressure levels (130 dBpeSPL), which is a sign of deafness. The apoptotic spiral ganglion neurons (SGNs) of the WD-STZ mice were significantly increased compared with those of the other three groups, indicating that SGN apoptosis resulted in hearing loss in STZ-induced diabetic ApoE KO mice fed with a WD. A significant loss of the stria vascularis cells was observed in the WD-STZ group compared with the CD-con mice. In the organ of Corti, few apoptotic hair cells were found in all the groups; however, no significant difference was observed. Therefore, we consider that the reduced hearing ability in the STZ-treated and WD-fed groups was attributed to the damage to the SGN and stria vascularis in the cochlea. Thus, our results indicated that ototoxicity by diabetes and/or dyslipidemia accelerated ARHL in ApoE KO mice, thereby suggesting the importance of appropriate treatment of patients with diabetes and/or dyslipidemia to prevent ARHL.

Accuracy of noncycloplegic refraction performed at school screening camps.

Purpose: The aim of this study was to compare noncycloplegic refraction performed in school camp with that performed in eye clinic in children aged 6-16 years. Methods: A prospective study of children with unaided vision <0.2 LogMAR who underwent noncycloplegic retinoscopy (NCR) and subjective refraction (SR) in camp and subsequently in eye clinic between February and March 2017 was performed. A masked optometrist performed refractions in both settings. The agreement between refraction values obtained at both settings was compared using the Bland-Altman analysis. Results: A total of 217 eyes were included in this study. Between the school camp and eye clinic, the mean absolute error ± standard deviation in spherical equivalent (SE) of NCR was 0.33 ± 0.4D and that of SR was 0.26 ± 0.5D. The limits of agreement for NCR were +0.91D to - 1.09D and for SR was +1.15D to -1.06D. The mean absolute error in SE was ≤0.5D in 92.62% eyes (95% confidence interval 88%-95%). Conclusion: A certain degree of variability exists between noncycloplegic refraction done in school camps and eye clinic. It was found to be accurate within 0.5D of SE in 92.62% eyes for refractive errors up to 4.5D of myopia, 3D of cylinder, and 1.5D of hyperopia.

Treatment of tapioca processing wastewater in a sequencing batch reactor: Mechanism of granule formation and performance.

The formation of aerobic granular sludge was carried out in a sequencing batch reactor (SBR) for tapioca processing wastewater treatment. The effect of organic loading rates (OLRs) in the range of 2.5-10.0 kg COD m-3 day-1 on the granulation was investigated. The size and settleability of the aerobic granular sludge increased with increasing OLR from 2.5 to 7.5 kg COD m-3 day-1. The mature granules had an average size of 2.5 mm and good settleability with the sludge volume index (SVI) lower than 50 mL g-1. The granules had a layered structure consisting of anoxic sludge core with nematodes and an outer aerobic layer surrounded by stalked ciliates. Removal efficiencies of chemical oxygen demand (COD) and NH4+-N reached 90.0%-93.0% and 86.6%-92.5%, respectively. Simultaneous nitrification and denitrification at the OLR of 7.5 kg COD m-3 day-1 resulted in the improvement of total nitrogen (TN) removal efficiency to 66.1%.