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Manciocco A.,National Research Council Italy | Calamandrei G.,Neurotoxicology and Neuroendocrinology Section | Alleva E.,Behavioural Neuroscience Section
Chemosphere | Year: 2014

Environmental contaminants are associated with a wide spectrum of pathological effects. Temperature increase affects ambient distribution and toxicity of these chemicals in the water environment, representing a potentially emerging problem for aquatic species with short-, medium- and long-term repercussions on human health through the food chain. We assessed peer-reviewed literature, including primary studies, review articles and organizational reports available. We focused on studies concerning toxicity of environmental pollutants within a global warming scenario. Existing knowledge on the effects that the increase of water temperature in a contaminated situation has on physiological mechanisms of aquatic organisms is presented. Altogether we consider the potential consequences for the human beings due to fish and shellfish consumption. Finally, we propose an etho-toxicological approach to study the effects of toxicants in conditions of thermal increase, using aquatic organisms as experimental models under laboratory controlled conditions. © 2014 Elsevier Ltd.

Huang H.,Italian Institute of Technology | Michetti C.,University of Rome La Sapienza | Busnelli M.,University of Milan | Busnelli M.,CNR Institute of Neuroscience | And 10 more authors.
Neuropsychopharmacology | Year: 2014

Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors. © 2014 American College of Neuropsychopharmacology.

Romano E.,Behavioural Neuroscience Section | Michetti C.,Neurotoxicology and Neuroendocrinology Section | Caruso A.,Neurotoxicology and Neuroendocrinology Section | Laviola G.,Behavioural Neuroscience Section | Scattoni M.L.,Neurotoxicology and Neuroendocrinology Section
PLoS ONE | Year: 2013

Reelin is a large secreted extracellular matrix glycoprotein playing an important role in early neurodevelopment. Several genetic studies found an association between RELN gene and increased risk of autism suggesting that reelin deficiency may be a vulnerability factor in its etiology. Moreover, a reduced reelin expression has been observed in several brain regions of subjects with Autism Spectrum Disorders. Since a number of reports have documented presence of vocal and neuromotor abnormalities in patients with autism and suggested that these dysfunctions predate the onset of the syndrome, we performed a fine-grain characterization of the neonatal vocal and motor repertoire in reelin mutant mice to explore the developmental precursors of the disorder. Our findings evidence a general delay in motor and vocal development in heterozygous (50% reduced reelin) and reeler (lacking reelin gene) mutant mice. As a whole, an increased number of calls characterized heterozygous pup's emission. Furthermore, the typical ontogenetic peak in the number of calls characterizing wild-type pups on postnatal day 4 appeared slightly delayed in heterozygous pups (to day 6) and was quite absent in reeler littermates, which exhibited a flat profile during development. We also detected a preferential use of a specific call category (two-components) by heterozygous and reeler mice at postnatal days 6 and 8 as compared to their wild-type littermates. With regard to the analysis of spontaneous movements, a differential profile emerged early in development among the three genotypes. While only slight coordination difficulties are exhibited by heterozygous pups, all indices of motor development appear delayed in reeler mice. Overall, our results evidence a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reelin mutant pups. © 2013 Romano et al.

Santucci D.,Behavioural Neuroscience Section | Kawano F.,Osaka University | Ohira T.,Osaka University | Terada M.,Japan Aerospace Exploration Agency | And 8 more authors.
PLoS ONE | Year: 2012

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occured only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity. © 2012 Santucci et al.

De Filippis B.,Behavioural Neuroscience Section | Musto M.,Behavioural Neuroscience Section | Altabella L.,Molecular and Cellular Imaging Section | Romano E.,Behavioural Neuroscience Section | And 2 more authors.
Neural Plasticity | Year: 2015

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases. Motor abnormalities represent a significant part of the spectrum of RTT symptoms. In the present study we investigated motor coordination and fine motor skill domains in MeCP2-308 female mice, a validated RTT model. This was complemented by the in vivo magnetic resonance spectroscopy (MRS) analysis of metabolic profile in behaviourally relevant brain areas. MeCP2-308 heterozygous female mice (Het, 10-12 months of age) were impaired in tasks validated for the assessment of purposeful and coordinated forepaw use (Morag test and Capellini handling task). A fine-grain analysis of spontaneous behaviour in the home-cage also revealed an abnormal handling pattern when interacting with the nesting material, reduced motivation to explore the environment, and increased time devoted to feeding in Het mice. The brain MRS evaluation highlighted decreased levels of bioenergetic metabolites in the striatal area in Het mice compared to controls. Present results confirm behavioural and brain alterations previously reported in MeCP2-308 males and identify novel endpoints on which the efficacy of innovative therapeutic strategies for RTT may be tested. © 2015 Bianca De Filippis et al.

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