Neuroscience
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Bexarotene has been proved to have neuroprotective effects in many animal models of neurological diseases. However, its neuroprotection in traumatic brain injury (TBI) is still unknown. This study aims to explore the neuroprotective effects of bexarotene on TBI and its possible mechanism. ⋯ No side-effects were detected after consecutive administration. Taken together, bexarotene inhibits the inflammatory response as well as cell apoptosis and improves the neurological function of mice after TBI partially through apolipoprotein E. This may make it a promising candidate for the therapeutic treatment after TBI.
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The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). ⋯ In this sense, factors that change central 5-HT levels may act as 'plasticity' rather than 'risk' factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk.
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Early stress in the form of repetitive neonatal pain, in infants born very preterm, is associated with long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and with poorer cognitive performance. Brain-derived neurotrophic factor (BDNF) which is important in synaptic plasticity and cognitive functions is reduced by stress. Therefore the BDNF Val66Met variant, which affects secretion of BDNF, may interact with early exposure to pain-related stress in children born very preterm, to differentially affect HPA regulation that in turn may be associated with altered cognitive performance. ⋯ In both boys and girls with the Met allele, higher salivary cortisol reactivity was correlated with lower IQ (r=-0.60; p=0.001) and poorer visual-motor integration (r=-0.48; p=0.008). Our findings show associations between lower BDNF availability (presence of the Met allele) and vulnerability to neonatal pain/stress in boys, but not girls. This exploratory study suggests new directions for research into possible mechanisms underlying how neonatal pain/stress is related to cognitive performance in children born very preterm.
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Volatile organic solvent abuse continues to be a worldwide health problem, including the neurobehavioral teratogenic sequelae of toluene abuse during pregnancy. Although abuse levels of prenatal toluene exposure can lead to a Fetal Solvent Syndrome, there is little research examining these effects on memory. Consumption of toluene can have detrimental effects on the developing hippocampus which could lead to specific spatial learning and memory deficits. ⋯ Male and female offspring (N=104) were observed in the MWM for 5days beginning on postnatal day (PN) 28 and again on PN44. While prenatal toluene-exposed animals did not differ in initial acquisition in the MWM, rats prenatally exposed to 12,000ppm toluene displayed performance deficits during a probe trial and in reversal learning on PN44. Overall, this study indicates that prenatal exposure to repeated inhaled abuse patterns of high concentrations of toluene can impair spatial memory function that persists into adolescence.