Deer antler extracts reduce amyloid-beta toxicity in a Caenorhabditis elegans model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Velvet antler extracts (VAE) are composed of a variety of active substances and growth factors, and have been reported to improve sleep quality and memory. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for VAE on Alzheimer's disease (AD) using a transgenic Caenorhabditis elegans model. MATERIALS AND METHODS: C. elegans were cultivated at 40% relative humidity on solid nematode growth medium (NGM) containing live E. coli (OP50) as the food source, with Strain N2 (normal) held at 20 °C and the CL4176s (transgenic) held at 16 °C. AD-like aggregation of Aß peptide in the CL4176s strain is induced by lifting the temperature to 25 °C. Nematodes were treated with three types of VAEs and Resveratrol (positive control). Analyses included qRT-PCR for quantification of gene transcripts of interest; ELISA for measuring levels of amyloid-ß protein; Thioflavin T fluorescent staining for localizing Aß depositions; assays for reactive oxygen species (ROS) and superoxide dismutase activity (SOD). RESULTS: VAEs reduced ß-amyloid peptide (Aß) toxicity in the transgenic C. elegans model. An enzymatically-digested VAE (EDVAE) was superior to both a cold-water VAE (CWVAE) and a hot-water VAE (HWVAE) from the same velvet antler. EDVAE treatment reduced the severity of the Aß-induced paralysis phenotype and decreased the amount of Aß deposits in the AD model nematodes, and these effects were found to be significantly better than that of the positive control Resveratrol. In addition, EDVAE treatment reduced production of ROS (induced by Aß), enhanced SOD activity, and elevated expression levels of antioxidant-related transcription factors, although it is not known whether these effects were achieved directly or indirectly. CONCLUSION: EDVAE had a protective role in Aß-induced toxicity in the transgenic AD nematodes, possibly through reducing accumulation of toxic Aß and enhancing the ability of nematodes to resist oxidative stress. Thus, EDVAE has potential to be an effective treatment to relieve the symptoms of AD.

Effects of Embryonic Exposure to Ethanol on Zebrafish Survival, Growth Pattern, Locomotor Activity and Retinal Development.

Alcohol intake can cause a wide range of visual system abnormalities. In this study, we characterized how ethanol affects the growth, external morphology and locomotion of zebrafish, particularly with regard to retinal development. Zebrafish embryos were divided into 5 groups and put into hatching liquid for 6 hours. The embryos from 4 groups were treated with varying concentrations of ethanol (0.5%, 1.5%, 2.5% and 3% by volume) from 6 to 24 hours post-fertilization. The toxic effects of ethanol on embryonic development were assessed by mortality, hatching rate and morphologic deformity. The effects of ethanol on locomotive activity were assessed by autonomous motion detection and swimming behavior analysis. The effects of ethanol on retinal morphology were assessed by histologic, immunohistochemical and electron microscopy analyses. Ethanol treatment increased the mortality and induced growth retardation in zebrafish larvae. The locomotive activities of zebrafish embryos/larvae were impeded by exposure to higher (1.5% and 2.5%) concentrations of ethanol. Embryos exposed to higher levels of ethanol at the early developmental stage had a reduction in eye size. The ethanol treatment disrupts the architecture of the retina and reduces retinal size. Embryos exposed to 2.5% concentration of ethanol had morphologic abnormalities of the photoreceptors. Ethanol exposure also inhibited retinal cell differentiation and proliferation, but did not affect apical epithelial polarity. These findings suggest that ethanol affects the growth and external morphology of zebrafish, and higher levels of ethanol exposure can cause defects of locomotor activity and photoreceptor development.

Zebrafish methanol exposure causes patterning defects and suppressive cell proliferation in retina.

PURPOSE: Methanol exposure have been shown to produce retinal abnormalities and visual dysfunctions in rodents and other mammals developing in utero. In this study, we characterized how methanol affects the retinal development in an ex utero embryonic system, the zebrafish. METHODS: Zebrafish embryos were raised for 24 hours in fish water supplemented with various concentrations of methanol at 6 hours after fertilisation. The effects of methanol on retinal morphology were assessed by histologic and immunohistochemical analyses. RESULTS: Zebrafish embryos exposed to moderate (3%) and high (4%) levels of methanol during early embryonic development had a small eye phenotype. Embryos exposed to high (4%) level of methanol had morphological abnormalities of the retinal pigment epithelia and the photoreceptors. Methanol exposure also caused inhibition of cell differentiation and proliferation in the retina at the early developmental stage. CONCLUSIONS: Low concentrations of methanol affect photoreceptor function but do not disturb retinal morphology. Higher levels of methanol exposure cause retinal patterning defects and a small eye phenotype.