73 research outputs found
Early postnatal ethanol exposure in mice induces sex-dependent memory impairment and reduction of hippocampal NMDA-R2B expression in adulthood
No full textDrinking alcohol during pregnancy is particularly detrimental for the developing brain and may cause a broad spectrum of cognitive and behavioral impairments, collectively known as fetal alcohol spectrum disorders (FASDs). While behavioral abnormalities and brain damage have been widely investigated in animal models of FASD, the sex differences in the vulnerability to perinatal ethanol exposure have received less consideration. Here we investigated the long-term behavioral and molecular effects of acute ethanol-binge like exposure during the early postnatal period (equivalent to the third trimester of human pregnancy) in adult male and female mice. CD1 mice received a single ethanol exposure on P7 and were analyzed starting from P60. We found that ethanol-exposed mice showed increased activity in the open field test and in the plus-maze test, regardless of the sex. Interestingly, only ethanol-exposed adult male mice exhibited memory impairment in the water maze and fear-conditioning tests. Remarkably, hippocampal levels of NMDA-R2B were reduced only in ethanol-exposed male, while total BDNF levels were increased in both male and female ethanol-exposed mice. Our data suggest a different susceptibility of early postnatal ethanol exposure in male and female CD1 mice
Chronic social defeat stress differentially regulates the expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice
No full textObjectives: Although stress is considered a primary risk factor for neuropsychiatric disorders, a majority of individuals are resilient to the effects of stress exposure and successfully adapt to adverse life events, while others, the so-called susceptible individuals, may have problems to properly adapt to environmental changes. However, the mechanisms underlying these different responses to stress exposure are poorly understood. Methods: Adult male C57BL/6J mice were exposed to chronic social defeat stress protocol and levels of brain derived neurotrophic factor (BDNF) transcripts and epigenetic modifying enzymes were analysed by real-time PCR in the hippocampus (HPC) and prefrontal cortex (PFC) of susceptible and resilient mice. Results: We found a selective reduction of BDNF-6 transcript in the HPC and an increase of BDNF-4 transcript in the PFC of susceptible mice. Moreover, susceptible mice showed a selective reduction of the g9a mRNA levels in the HPC, while HDAC-5 and DNMT3a mRNA levels were specifically reduced in the PFC. Conclusions: Overall, our results, showing a different expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice, suggest that stress resilience is not simply a lack of activation of stress-related pathways, but is related to the activation of additional different specific mechanisms
Stress, microRNAs, and stress-related psychiatric disorders: an overview
No full textStress is a major risk factor for psychiatric disorders. During and after exposure to stressors, the stress response may have pro- or maladaptive consequences, depending on several factors related to the individual response and nature of the stressor. However, the mechanisms mediating the long-term effects of exposure to stress, which may ultimately lead to the development of stress-related disorders, are still largely unknown. Epigenetic mechanisms have been shown to mediate the effects of the environment on brain gene expression and behavior. MicroRNAs, small non-coding RNAs estimated to control the expression of about 60% of all genes by post-transcriptional regulation, are a fundamental epigenetic mechanism. Many microRNAs are expressed in the brain, where they work as fine-tuners of gene expression, with a key role in the regulation of homeostatic balance, and a likely influence on pro- or maladaptive brain changes. Here we have selected a number of microRNAs, which have been strongly implicated as mediators of the effects of stress in the brain and in the development of stress-related psychiatric disorders. For all of them recent evidence is reported, obtained from rodent stress models, manipulation of microRNAs levels with related behavioral changes, and clinical studies of stress-related psychiatric disorders. Moreover, we have performed a bioinformatic analysis of the predicted brain-expressed target genes of the microRNAs discussed, and found a central role for mechanisms involved in the regulation of synaptic function. The complex regulatory role of microRNAs has suggested their use as biomarkers for diagnosis and treatment response, as well as possible therapeutic drugs. While, microRNA-based diagnostics have registered advancements, particularly in oncology and other fields, and many biotech companies have launched miRNA therapeutics in their development pipeline, the development of microRNA-based tests and drugs for brain disorders is comparatively slower
Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain.
No full textBACKGROUND: Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occurring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration. METHODS AND FINDINGS: P7 mice were treated with a single dose of ethanol (5 g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot (n = 4-7/group). Density of Fluoro-Jade B-positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus (n = 5-6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice (n = 31-34/group). Nicotinamide reduced the activation of caspase-3 (85.14 +/- 4.1%) and the release of cytochrome-c (80.78 +/- 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice. CONCLUSIONS: Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS
16. Medici Bizantini (Oribasio di Pergamo, Aezio d'Amida, Alessandro di Tralle, Paolo d'Egina, Leone Medico), a cura di Garzya (Antonio), De Lucia (Roberto), Guardasole (Alessia), Ieraci Bio (Anna Maria), Lamagna (Mario), Romano (Roberto) (Classici Greci, Autori della tarda antiquità e dell'età bizantina)
No full textDemont Paul. 16. Medici Bizantini (Oribasio di Pergamo, Aezio d'Amida, Alessandro di Tralle, Paolo d'Egina, Leone Medico), a cura di Garzya (Antonio), De Lucia (Roberto), Guardasole (Alessia), Ieraci Bio (Anna Maria), Lamagna (Mario), Romano (Roberto) (Classici Greci, Autori della tarda antiquità e dell'età bizantina). In: Revue des Études Grecques, tome 120, fascicule 2, Juillet-décembre 2007. pp. 829-830
Fallen Idols. State Failure and the Weakness of Authoritarianism
No full textThe Author tackles the RoA thesis, and opposes to it the ‘Weakness of Authoritarianism’ (WoA) argument. According to the latter, the authoritarian regimes are politically poorly institutionalized, as it is proved by their incapacity to transmit the political power peacefully and smoothly. Therefore, the authoritarian regimes are by definition on the verge of breakdown, they are constitutively weak and they can only precariously survive only as long as some regime factors (a political party, a bureaucracy penetrated by the dominant elite, a loyal and efficient coercive apparatus) manage to stem social and political mobilization against the power incumbents. The institutionalization of the coercive apparatus should not be considered in itself, but together with other aspects of the political institutionalization of a given regime. Some evidence is drawn from the recent cases of regime breakdown in the Middle East and North Africa
Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum
No full textFetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways
Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice
No full textStress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice
Sex and Circadian Rhythm Dependent Behavioral Effects of Chronic Stress in Mice and Modulation of Clock Genes in the Prefrontal Cortex
No full textBehavioral stress is a recognized triggering factor for systemic diseases, including psychiatric disorders. The stress response is subjected to circadian regulation and many factors shape the susceptibility to its maladaptive consequences, including the biological sex. Accordingly, circadian dysregulation of the stress response, often occurring in a sexually dimorphic manner, is typically associated with psychiatric disorders. However, the interaction between stress, sex, circadian phases, and behavior is still largely unknown. Here, we used the chronic restraint stress (CRS) model in male and female mice to assess the impact of sex and circadian phases on the behavioral consequences of chronic stress. Animals were stressed either in the light or dark phase, and anxious-/depressive-/anhedonic-like behaviors were assessed. Associated transcriptional changes in clock genes were measured in the prefrontal cortex. A significant interaction of stress, sex, and circadian phase was found in most of the parameters evaluated, with no behavioral response to stress in males stressed in the dark phase, and an exaggerated response in females stressed in the dark phase compared to the light phase. We also found some molecular changes in corticosterone serum levels and expression of clock genes in the prefrontal cortex
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