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Alejandra Kun, Fernando González-Camacho, Silvia Hernández, Alexandra Moreno-García, Olga Calero, Miguel Calero
The study of brain pathology by fluorescence microscopy finds in the autofluorescence of the tissue an additional difficulty for the recognition of markers of interest. In particular, in the immunofluorescence study of brains from Alzheimer's disease (AD) patients, several approaches have been attempted to eliminate or mask the presence of autofluorescent aggregates. In the present work, we propose a method to characterize by fluorescent microscopy senile plaques discriminating them from autofluorescent aggregates, such as lipofuscin granules...
2018: Methods in Molecular Biology
Yong Peng, Zhong-Hua Tong, Han-Juan Chong, Xin-Yue Shao
Ionic liquids (ILs) are gradually concerned due to their potential environmental and health risks. In this work, the chronic effects of imidazolium-based ILs, using [C14 mim]Br as a representative, were evaluated using model animal Caenorhabditis elegans. Our results show that prolonged exposure (72 h) of ILs to the nematodes at concentrations of 5 and 10 mg/L induced adverse effects on the growth, locomotive behaviors and development. To explore the toxicity mechanism, lipofuscin content, ROS level and the expressions of five superoxide dismutase (SOD) genes were determined after the prolonged exposure...
May 29, 2018: Chemosphere
Boglarka Racz, Andras Varadi, Jian Kong, Rando Allikmets, Paul G Pearson, Graham Johnson, Christopher L Cioffi, Konstantin Petrukhin
A primary pathological defect in the heritable eye disorder Stargardt disease is excessive accumulation of cytotoxic lipofuscin bisretinoids in the retina. Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) matches the age-dependent increase in the incidence of the atrophic (dry) form of age-related macular degeneration (AMD) and therefore may be one of several pathogenic factors contributing to AMD progression. Lipofuscin bisretinoid synthesis in the retina depends on the influx of serum retinol from the circulation into the RPE...
June 5, 2018: Journal of Biological Chemistry
Chun Ming How, Shang-Wei Li, Vivian Hsiu-Chuan Liao
Triadimenol, an agricultural fungicide, is an emerging environmental concern due to its wide usage, detection in the environment, and its chemical persistency. Triadimenol has been found to disrupt endocrine signaling and alter function of several transcription factors, yet its age-related toxicity effects remain unclear. This study used Caenorhabditis elegans as an in vivo model organism to elucidate the age-related effects of triadimenol and its underlying mechanisms. The results showed that chronic exposure to triadimenol at environmentally relevant concentrations (3, 30, and 300 μg/L) adversely affected several toxicity endpoints including growth, total brood size, and locomotive behaviors...
June 1, 2018: Science of the Total Environment
Ekatherine Prokopiou, Panagiotis Kolovos, Maria Kalogerou, Anastasia Neokleous, Orthodoxia Nicolaou, Kleitos Sokratous, Kyriacos Kyriacou, Tassos Georgiou
Purpose: To evaluate the therapeutic effects of omega-3 (ω3) fatty acids on retinal degeneration in the ABCA4-/- model of Stargardt disease when the blood level of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is between 1 and 1.5. Methods: Eight-month-old mice were allocated to three groups: wild type (129S1), ABCA4-/- untreated, and ABCA4-/- ω3 treated. ω3 treatment lasted 3 months and comprised daily gavage administration of EPA and docosahexaenoic acid (DHA)...
June 1, 2018: Investigative Ophthalmology & Visual Science
Xiaoli Wang, Jie Yang, Hui Li, Shu Guo, Muhammad Tariq, Haibo Chen, Chen Wang, Yongdi Liu
In order to gain insights into the chronic effects and mechanisms of hexabromocyclododecane (HBCD), the animal model Caenorhabditis elegans (C. elegans) was chosen for toxicity study. Multiple endpoints, including the physiological (growth and locomotion behaviors), biochemical (reactive oxygen species (ROS) production, lipofuscin accumulation, and cell apoptosis), and molecular (stress-related gene expressions) levels, were tested by chronic exposure for 10 d to low concentrations of HBCD (0.2 nM-200 nM)...
May 25, 2018: Chemosphere
Sruti Rayaprolu, Yasin B Seven, John Howard, Colin Duffy, Marcelle Altshuler, Christina Moloney, Benoit I Giasson, Jada Lewis
Loss-of-function mutations in ATP13A2 are associated with three neurodegenerative diseases: a rare form of Parkinson's disease termed Kufor-Rakeb syndrome (KRS), a lysosomal storage disorder termed neuronal ceroid lipofuscinosis (NCL), and a form of hereditary spastic paraplegia (HSP). Furthermore, recent data suggests that heterozygous carriers of mutations in ATP13A2 may confer risk for the development of Parkinson's disease, similar to the association of mutations in glucocerebrosidase (GBA) with both Parkinson's disease and Gaucher's disease, a lysosomal storage disorder...
May 31, 2018: Molecular and Cellular Neurosciences
Anna Hoerder-Suabedissen, Kim V Korrell, Shuichi Hayashi, Alexander Jeans, Denise M O Ramirez, Eleanor Grant, Helen C Christian, Ege T Kavalali, Michael C Wilson, Zoltán Molnár
Synaptosomal associated protein 25 kDa (SNAP25) is an essential component of the SNARE complex regulating synaptic vesicle fusion. SNAP25 deficiency has been implicated in a variety of cognitive disorders. We ablated SNAP25 from selected neuronal populations by generating a transgenic mouse (B6-Snap25tm3mcw (Snap25-flox)) with LoxP sites flanking exon5a/5b. In the presence of Cre-recombinase, Snap25-flox is recombined to a truncated transcript. Evoked synaptic vesicle release is severely reduced in Snap25 conditional knockout (cKO) neurons as shown by live cell imaging of synaptic vesicle fusion and whole cell patch clamp recordings in cultured hippocampal neurons...
May 30, 2018: Cerebral Cortex
Maarjaliis Paavo, Jin Zhao, Hye Jin Kim, Winston Lee, Jana Zernant, Carolyn Cai, Rando Allikmets, Stephen H Tsang, Janet R Sparrow
Purpose: We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods: Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500-680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope...
May 1, 2018: Investigative Ophthalmology & Visual Science
Yue Zhou, Qinggang Xu, Xinghua Zhou, Shuang Song, Beiwei Zhu
Bioactive peptides derived from mussels have multiple healthcare functions. Herein, we aimed to examine the effects of mussel peptide preparation on lifespan, stress resistance, apoptosis and aging in Caenorhabditis elegans. Lifespan was determined by counting the number of surviving nematodes daily. ROS level and lipofuscin were measured using a fluorescent microscope. The mussel protein was prepared and hydrolyzed, and then fractionated by ultrafiltration. The fraction (<3 kDa) was purified by gel filtration to obtain the bioactive peptides, and the peptide sequences included in the fractions were identified, which were mostly composed of peptides with <20 amino acid residues...
May 24, 2018: Food & Function
Abhilasha Maheshwari, Paul T Finger
PURPOSE: To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy. METHODS: Retrospective interventional case series including 170 consecutive patients treated with 103 Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology. RESULTS: The mean initial tumor thickness was 3...
May 1, 2018: European Journal of Ophthalmology
Tatiana B Feldman, Marina A Yakovleva, Andrey V Larichev, Patimat M Arbukhanova, Alexandra Sh Radchenko, Sergey A Borzenok, Vladimir A Kuzmin, Mikhail A Ostrovsky
PURPOSE: The aim of this work is the determination of quantitative diagnostic criteria based on the spectral characteristics of fundus autofluorescence to detect early stages of degeneration in the retina and retinal pigment epithelium (RPE). METHODS: RPE cell suspension samples were obtained from the cadaver eyes with and without signs of age-related macular degeneration (AMD). Fluorescence analysis at an excitation wavelength of 488 nm was performed. The fluorescence lifetimes of lipofuscin-granule fluorophores were measured by counting time-correlated photon method...
May 22, 2018: Eye
Durmuş Bolat, Aytül Kürüm, Sıla Canpolat
The pineal gland is a neuroendocrine organ associated with photoperiodic regulation in mammals. The aim of this study was to evaluate the pineal gland at the pre-pubertal, pubertal and post-pubertal periods by means of morphology and stereology. The study examined at total of 24 ovine pineal glands collected from healthy female Akkaraman breed. Thick sections (40 μm) were cut and treated with synaptophysin. Following each thick section, six consecutive sections at a thickness of 5 μm were cut. Each thin section was stained with one of the following dyes: Crossman's modified triple dye, glial fibrillary acidic protein (GFAP), melatonin marker, periodic acid-Schiff, Von Kossa and AgNOR...
May 18, 2018: Anatomia, Histologia, Embryologia
Ching-Long Chen, Yi-Hao Chen, Chang-Min Liang, Ming-Cheng Tai, Da-Wen Lu, Jiann-Torng Chen
Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved...
May 9, 2018: International Journal of Molecular Sciences
Ulises Urzua, Carlos Chacon, Renato Espinoza, Sebastián Martínez, Nicole Hernandez
The progressive decline of the ovarian follicle pool leads to reproductive ageing. The latter is accompanied by age-related disorders, including various types of cancer. In fact, the highest rates of ovarian cancer (OC) occur at postmenopause while OC risk is significantly modulated by parity records during previous fertile life. We approached the age-parity relationship in the C57BL/6 mouse model and herein describe the presence of nonheme iron (hemosiderin) and deposits of the "age pigment" lipofuscin in reproductively aged mouse ovaries by applying conventional histochemical methods and autofluorescence...
2018: Analytical Cellular Pathology (Amsterdam)
Dimuth N Gunawardane, Philip W Allen
Peritoneal lipofuscinosis is a very rarely recognized condition occurring during pregnancy characterized by brown pigmentation of the omentum and peritoneum, a decidual reaction and benign mesothelial cells. The iron negative pigment, which is likely to be confused with hemosiderin in the hematoxylin and eosin stain, is lipofuscin. The seminar case, apparently the third published, arose in a 37-year-old woman who presented in October 2015 at 24 weeks pregnancy with abdominal pain. Investigations revealed a ruptured left ovarian cyst and rising serum carcinoembryonic antige levels...
April 30, 2018: Advances in Anatomic Pathology
Wennan Lu, Néstor M Gómez, Jason C Lim, Sonia Guha, Ann O'Brien-Jenkins, Erin E Coffey, Keith E Campagno, Stuart A McCaughey, Alan M Laties, Leif G Carlsson, Claire H Mitchell
The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE) cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt's disease, an early onset retinal degeneration...
2018: Frontiers in Pharmacology
Suryanarayan Biswal, Kalpana Kumari Barhwal, Debashree Das, Richa Dhingra, Nilima Dhingra, Tapas Chanda Nag, Sunil Kumar Hota
Chronic hypoxic stress results in deposition of lipofuscin granules in the CA3 region of hippocampal neurons which contributes to neurodegeneration and accelerated neuronal aging. Oxidative stress and mitophagy during hypoxia are crucial to cause aggregation of these lipofuscin granules in hypoxic neurons. Salidroside, a glucoside derivative of β-Tyrosol, has been reported to protect hypoxic neurons through maintenance of mitochondrial activity. The present study is aimed at investigating the potential of Salidroside in preventing mitophagy during chronic hypoxia and identification of the molecular targets and underlying signaling mechanisms...
April 30, 2018: Neurobiology of Disease
Keiko Ueda, Hye Jin Kim, Jin Zhao, Janet R Sparrow
Retinaldehyde adducts (bisretinoids) accumulate in retinal pigment epithelial (RPE) cells as lipofuscin. Bisretinoids are implicated in some inherited and age-related forms of macular degeneration that lead to the death of RPE cells and diminished vision. By comparing albino and black-eyed mice and by rearing mice in darkness and in cyclic light, evidence indicates that bisretinoid fluorophores undergo photodegradation in the eye (Ueda et al. Proc Natl Acad Sci 113:6904-6909, 2016). Given that the photodegradation products modify and impair cellular and extracellular molecules, these processes likely impart cumulative damage to retina...
2018: Advances in Experimental Medicine and Biology
Julia Rodríguez-Castelán, Maribel Méndez-Tepepa, Jorge Rodríguez-Antolín, Francisco Castelán, Estela Cuevas-Romero
Dyslipidaemia and hyperglycaemia are associated with ovarian failure and both have been related to hypothyroidism. Hypothyroidism promotes anovulation and ovarian cysts in women and reduces the size of follicles and the expression of aromatase in the ovary of rabbits. Considering that ovarian steroidogenesis and ovulation depend on lipid metabolism and signalling, the aim of the present study was to analyse the effect of hypothyroidism on the lipid content and expression of peroxisome proliferator-activated receptor (PPAR) δ in the ovary...
May 3, 2018: Reproduction, Fertility, and Development
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