Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice

The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25–20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity

EB1 Is Required for Spindle Symmetry in Mammalian Mitosis

Most information about the roles of the adenomatous polyposis coli protein (APC) and its binding partner EB1 in mitotic cells has come from siRNA studies. These suggest functions in chromosomal segregation and spindle positioning whose loss might contribute to tumourigenesis in cancers initiated by APC mutation. However, siRNA-based approaches have drawbacks associated with the time taken to achieve significant expression knockdown and the pleiotropic effects of EB1 and APC gene knockdown. Here we describe the effects of microinjecting APC- or EB1- specific monoclonal antibodies and a dominant-negative EB1 protein fragment into mammalian mitotic cells. The phenotypes observed were consistent with the roles proposed for EB1 and APC in chromosomal segregation in previous work. However, EB1 antibody injection also revealed two novel mitotic phenotypes, anaphase-specific cortical blebbing and asymmetric spindle pole movement. The daughters of microinjected cells displayed inequalities in microtubule content, with the greatest differences seen in the products of mitoses that showed the severest asymmetry in spindle pole movement. Daughters that inherited the least mobile pole contained the fewest microtubules, consistent with a role for EB1 in processes that promote equality of astral microtubule function at both poles in a spindle. We propose that these novel phenotypes represent APC-independent roles for EB1 in spindle pole function and the regulation of cortical contractility in the later stages of mitosis. Our work confirms that EB1 and APC have important mitotic roles, the loss of which could contribute to CIN in colorectal tumour cells

Synergistic effects of seed disperser and predator loss on recruitment success and long-term consequences for carbon stocks in tropical rainforests

Made available in DSpace on 2018-12-11T17:33:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01The extinction of large frugivores has consequences for the recruitment of large-seeded plants with potential lasting effects on carbon storage in tropical rainforests. However, previous studies relating frugivore defaunation to changes in carbon storage ignore potential compensation by redundant frugivores and the effects of seed predators on plant recruitment. Based on empirical data of the recruitment success of a large-seeded hardwood tree species (Cryptocarya mandioccana, Lauraceae) across a defaunation gradient of seed dispersers and predators, we show that defaunation increases both seed dispersal limitation and seed predation. Depending on the level of seed predator loss, plant recruitment is reduced by 70.7-94.9% as a result of the loss of seed dispersers. The loss of large seed predators increases the net seed mortality by 7-30% due to the increased abundance of small granivorous rodents. The loss of large seed dispersers can be buffered by the compensatory effects of smaller frugivores in seed removal, but it is not sufficient to prevent a decrease in plant recruitment. We show that the conservation of both seed predators and dispersers is necessary for the recruitment of large-seeded plants. Since these plants contribute substantially to carbon stocks, defaunation can jeopardize the maintenance of tropical forest carbon storage.Universidade Estadual Paulista (UNESP) Instituto de Biociências Departamento de Zoologia Laboratório de Primatologia, Avenida 24A, CP199 1515Universidade Estadual Paulista (UNESP) Instituto de Biociências Departamento de Ecologia Laboratório de Biologia da Conservação, Avenida 24A, 1515 CP199Escola Superior de Agricultura Luiz de Queiroz (ESALQ) Universidade de São Paulo (USP) Departamento de Ciências Florestais, Avenida Pádua Dias, 11Universidade Estadual Paulista (UNESP) Instituto de Biociências Departamento de Zoologia Laboratório de Primatologia, Avenida 24A, CP199 1515Universidade Estadual Paulista (UNESP) Instituto de Biociências Departamento de Ecologia Laboratório de Biologia da Conservação, Avenida 24A, 1515 CP19

AMAZONIA CAMTRAP: a dataset of mammal, bird, and reptile species recorded with camera traps in the Amazon forest

The Amazon forest has the highest biodiversity on earth. However, information on Amazonian vertebrate diversity is still deficient and scattered across the published, peer-reviewed and grey literature and in unpublished raw data. Camera traps are an effective non-invasive method of surveying vertebrates, applicable to different scales of time and space. In this study, we organized and standardized camera trap records from different Amazon regions to compile the most extensive dataset of inventories of mammal, bird and reptile species ever assembled for the area. The complete dataset comprises 154,123 records of 317 species (185 birds, 119 mammals and 13 reptiles) gathered from surveys from the Amazonian portion of eight countries (Brazil, Bolivia, Colombia, Ecuador, French Guiana, Peru, Suriname and Venezuela). The most frequently recorded species per taxa were: mammals - Cuniculus paca (11,907 records); birds - Pauxi tuberosa (3,713 records); and reptiles - Tupinambis teguixin (716 records). The information detailed in this data paper opens-up opportunities for new ecological studies at different spatial and temporal scales, allowing for a more accurate evaluation of the effects of habitat loss, fragmentation, climate change and other human-mediated defaunation processes in one of the most important and threatened tropical environments in the world. The dataset is not copyright restricted; please cite this data-paper when using its data in publications and we also request that researchers and educators inform us of how they are using this data

Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure

<div><p>The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse’s lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as “Free radical scavenging”. We confirmed six of these changes by droplet digital PCR including the caspase <i>Casp3</i> and Wnt transcription factor <i>Tcf7l2</i>. The top pathway for all methylation-affected genes was “Peroxisome biogenesis”; we confirmed differential DNA methylation in the <i>Acca1</i> thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.</p></div

Low Dose Prenatal Ethanol Exposure Induces Anxiety-Like Behaviour and Alters Dendritic Morphology in the Basolateral Amygdala of Rat Offspring

Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control) or 6% (vol/vol) ethanol (EtOH) throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult) or 15 months (Aged) of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour