Effects of subcutaneous LPS injection on gestational length and intrauterine and neonatal mortality in mice

BACKGROUND Infection during pregnancy can predispose offspring to develop various psychiatric disorders such as depression in later life. In order to investigate the potential mechanisms underlying these associations, animal models of maternal infection have been employed. As such, lipopolysaccharide (LPS) has been commonly used to mimic a bacterial infection in pregnant mice. OBJECTIVE The original aim of our study was to investigate the effects of different doses of subcutaneous LPS administration on affective behavior in adult mouse offspring. In the present paper, however, we report that subcutaneous LPS administration has a profound impact on gestational length, litter size, and perinatal mortality in the offspring, even at a relatively low dose. METHODS Pregnant mice were randomly divided into 3 groups, receiving either a high (2 mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of subcutaneous injection. Subsequently, the effects on gestational length, litter size, and perinatal mortality in the offspring were assessed. RESULTS After subcutaneous injection with a high dose of LPS, we observed a significant decrease in gestational length and an increase in neonatal mortality. When the low dose was administered, a tendency towards a reduced litter size was observed, most likely reflecting increased intrauterine mortality in response to prenatal maternal LPS exposure. CONCLUSIONS We showed that subcutaneous administration of 2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided because of high offspring mortality rates, whereas subcutaneous injection of 0.5 mg/kg LPS seems to result in reabsorption of the fetuses

Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage

Placental and fetal hypoxia caused by perinatal hypoxic-ischemic events are major causes of stillbirth, neonatal morbidity, and long-term neurological sequelae among surviving neonates. Brain hypoxia and associated pathological processes such as excitotoxicity, apoptosis, necrosis, and inflammation, are associated with lasting disruptions in epigenetic control of gene expression contributing to neurological dysfunction. Recent studies have pointed to DNA (de)methylation, histone modifications, and non-coding RNAs as crucial components of hypoxic-ischemic encephalopathy (HIE). The understanding of epigenetic dysregulation in HIE is essential in the development of new clinical interventions for perinatal HIE. Here, we summarize our current understanding of epigenetic mechanisms underlying the molecular pathology of HI brain damage and its clinical implications in terms of new diagnostic, prognostic, and therapeutic tools.Fil: Bustelo, Martí. Universidad de Buenos Aires; Argentina. Maastricht University Medical Center; Países Bajos. Universidad Católica de Cuyo - Sede San Juan; ArgentinaFil: Barkhuizen, Melinda. Maastricht University Medical Center; Países BajosFil: van den Hove, Daniel L. A.. Universiteit Maastricht.; Países BajosFil: Steinbusch, Harry Wilhelm. M.. Universiteit Maastricht.; Países BajosFil: Bruno, Martin. Universidad Católica de Cuyo - Sede San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Loidl, Cesar Fabian. Universidad Catolica de Cuyo - Sede San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Gavilanes, Antonio W. Danilo. Maastricht University Medical Cente; Países Bajo

Seasonal changes in a sandy beach fish assemblage at Canto Grande, Santa Catarina, South Brazil

Copyright © 2004 Coastal Education and Research Foundation (CERF).Neste trabalho realizaramse amostragens, com uma rede de praia, de modo a estudar a comunidade de peixes de substrato arenoso na enseada de Canto Grande, Santa Catarina, Brasil. As amostragens realizaramse em intervalos de 3 horas durante períodos de 24 h, numa base bimensal, entre Abril de 1996 e Fevereiro de 1997. Verificouse existir uma variação sazonal no número de espécies, densidade de peixes e biomassa, tendo os valores mais elevados ocorrido em Fevereiro (38 espécies, 257.6 peixes 1000 mˉ², 2286.4 g 1000 mˉ²). Recolheuse um total de 67 espécies, pertencentes a 56 géneros e a 33 famílias, sendo a comunidade dominada por sete espécies pertencentes a três famílias: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola e Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus e Lycengraulis grossidens (Engraulidae). Tanto a diversidade de espécies (H′) como a equitabilidade (J′) foram médias a elevadas ao longo do ano devido à baixa dominância. A maior mudança na estrutura da comunidade ocorreu entre os meses de Inverno (Julho e Agosto) e as outras estações. Nenhuma das espécies dominantes pode ser classificada como residente. Os principais predadores foram Pomatomus saltator (Inverno) e Trichiurus lepturus (Verão). A maior parte das espécies observadas foram ou peixes juvenis ou espécies pelágicas de pequeno tamanho e fortemente gregárias.ABSTRACT: A shallow-water fish assemblage, over a soft, sandy bottom, at Canto Grande, Santa Catarina, Brazil, was sampled with a beach seine. Sampling was undertaken at 3 h intervals over 24 h on a bimonthly basis between April 1996 and February 1997. There was a seasonal variation in the number of species, density of fishes and biomass with the highest values in February (38 species, 257.6 fish 1000 mˉ², 2286.4 g 1000 mˉ²). A total of 67 species, belonging to 56 genera and 33 families were collected and the assemblage was dominated by seven species belonging to three families: Atherinella brasiliensis (Atherinidae); Brevoortia pectinata, Harengula clupeola and Sardinella brasiliensis (Clupeidae); Anchoviella lepidontostole, Cetengraulis edentulus and Lycengraulis grossidens (Engraulidae). Species diversity (H′) and equitability (J′) were medium to high throughout the year due to the low dominance. The largest change in the assemblage structure occurred between winter months (July and August) and the other seasons. None of the dominant species can be classified as a resident. Main predators were Pomatomus saltator (winter) and Trichiurus lepturus (summer). Most of the species observed were either juvenile fish or small pelagic and strongly gregarious species

CERT\u3csub\u3eL\u3c/sub\u3e Reduces C16 Ceramide, Amyloid-β Levels, and Inflammation in a Model of Alzheimer’s Disease

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer\u27s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain. METHODS: A plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno-associated virus (AAV) in a mouse model of familial AD (5xFAD). Ten weeks after transduction, animals were challenged with behavior tests for memory, anxiety, and locomotion. At week 12, brains were investigated for sphingolipid levels by mass spectrometry, plaques, and neuroinflammation by immunohistochemistry, gene expression, and/or immunoassay. RESULTS: Here, we report that CERTL binds to APP, modifies Aβ aggregation, and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male 5xFAD mice. CERTL in vivo over-expression has a mild effect on animal locomotion, decreases Aβ formation, and modulates microglia by decreasing their pro-inflammatory phenotype. CONCLUSION: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases

Carbohydrate Metabolism Is Essential for the Colonization of Streptococcus thermophilus in the Digestive Tract of Gnotobiotic Rats

Streptococcus thermophilus is the archetype of lactose-adapted bacterium and so far, its sugar metabolism has been mainly investigated in vitro. The objective of this work was to study the impact of lactose and lactose permease on S. thermophilus physiology in the gastrointestinal tract (GIT) of gnotobiotic rats. We used rats mono-associated with LMD-9 strain and receiving 4.5% lactose. This model allowed the analysis of colonization curves of LMD-9, its metabolic profile, its production of lactate and its interaction with the colon epithelium. Lactose induced a rapid and high level of S. thermophilus in the GIT, where its activity led to 49 mM of intra-luminal L-lactate that was related to the induction of mono-carboxylic transporter mRNAs (SLC16A1 and SLC5A8) and p27Kip1 cell cycle arrest protein in epithelial cells. In the presence of a continuous lactose supply, S. thermophilus recruited proteins involved in glycolysis and induced the metabolism of alternative sugars as sucrose, galactose, and glycogen. Moreover, inactivation of the lactose transporter, LacS, delayed S. thermophilus colonization. Our results show i/that lactose constitutes a limiting factor for colonization of S. thermophilus, ii/that activation of enzymes involved in carbohydrate metabolism constitutes the metabolic signature of S. thermophilus in the GIT, iii/that the production of lactate settles the dialogue with colon epithelium. We propose a metabolic model of management of carbohydrate resources by S. thermophilus in the GIT. Our results are in accord with the rationale that nutritional allegation via consumption of yogurt alleviates the symptoms of lactose intolerance

CERTL reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer’s disease

Background: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain. Methods: A plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno-associated virus (AAV) in a mouse model of familial AD (5xFAD). Ten weeks after transduction, animals were challenged with behavior tests for memory, anxiety, and locomotion. At week 12, brains were investigated for sphingolipid levels by mass spectrometry, plaques, and neuroinflammation by immunohistochemistry, gene expression, and/or immunoassay. Results: Here, we report that CERTL binds to APP, modifies Aβ aggregation, and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male 5xFAD mice. CERTL in vivo over-expression has a mild effect on animal locomotion, decreases Aβ formation, and modulates microglia by decreasing their pro-inflammatory phenotype. Conclusion: Our results demonstrate a crucial role of CERTL in r

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online