International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
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Int. J. Dev. Neurosci. · Oct 2016
Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats.
Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. ⋯ Thus, our results indicate that VPA disrupts the AR ontogeny in the developing cerebellum in an age and region specific manner in male and female rats. Future epigenetic studies including the evaluation of histone deacetylases (HDAC's) might shed light these results as HDAC's are expressed by Purkinje neurons, interact with the AR and are VPA targets. This work contributes to the understanding of the cerebellar development and it might help to understand the role of the cerebellum in neurodevelopmental disorders such as autism.
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Int. J. Dev. Neurosci. · Jun 2016
ReviewOf rodents and humans: A comparative review of the neurobehavioral effects of early life SSRI exposure in preclinical and clinical research.
Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for the past 25 years. SSRIs act via blockade of the presynaptic serotonin transporter and result in a transient increase in synaptic serotonin. Long-lasting changes in cellular function such as serotonergic transmission, neurogenesis, and epigenetics, are thought to underlie the therapeutic benefits of SSRIs. ⋯ We review recent evidence indicating that perinatal SSRI exposure perturbs the developing limbic system, including altered serotonergic transmission, neurogenesis, and epigenetic processes in the hippocampus, which may contribute to behavioral domains (e.g., sociability, cognition, anxiety, and behavioral despair) that are affected by perinatal SSRI treatment. Identifying the molecular mechanisms that underlie the deleterious behavioral effects of perinatal SSRI exposure may highlight biological mechanisms in the etiology of mood disorders. Moreover, because recent studies suggest that certain individuals may be more susceptible to the negative consequences of early life SSRI exposure than others, understanding mechanisms that drive such susceptibility could lead to individualized treatment strategies for depressed women who are or plan to become pregnant.
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Int. J. Dev. Neurosci. · Jun 2016
Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring.
Diabetes in pregnancy has a detrimental effect on central nervous system (CNS) development and is associated with an increased risk of short- and long-term neurocognitive impairment in the offspring. This study aimed to investigate the effect of maternal diabetes and also insulin treatment on the numerical density of apoptotic cells in rat neonate's hippocampi during the first two postnatal weeks. ⋯ Our data indicate that diabetes in pregnancy induce the neuronal cell apoptosis in offspring hippocampus. Furthermore, the maternal glycaemia control by insulin treatment in the most cases normalized these effects.
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Int. J. Dev. Neurosci. · Apr 2016
Longitudinal outcome and recovery of social problems after pediatric traumatic brain injury (TBI): Contribution of brain insult and family environment.
Pediatric traumatic brain injury (TBI) can result in a range of social impairments, however longitudinal recovery is not well characterized, and clinicians are poorly equipped to identify children at risk for persisting difficulties. Using a longitudinal prospective design, this study aimed to evaluate the contribution of injury and non-injury related risk and resilience factors to longitudinal outcome and recovery of social problems from 12- to 24-months post-TBI. 78 children with TBI (injury age: 5.0-15.0 years) and 40 age and gender-matched typically developing (TD) children underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury (M=39.25, SD=27.64 days). At 12 and 24-months post- injury, parents completed questionnaires rating their child's social functioning, and environmental factors including socioeconomic status, caregiver mental health and family functioning. ⋯ Pre-injury environment and SWI did not significantly contribute to outcome at 24-months, however concurrent caregiver mental health and family functioning explained a large and significant proportion of variance in these outcomes. Overall, this study shows that longitudinal recovery profiles differ as a function of injury severity, with evidence for late-emerging social problems among children with severe TBI. Poorer long-term social outcomes were associated with family dysfunction and poorer caregiver mental health at 24-months post injury, suggesting that efforts to optimize the child's environment and bolster family coping resources may enhance recovery of social problems following pediatric TBI.
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Int. J. Dev. Neurosci. · Apr 2016
Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalitis (EAE) is an inflammatory demyelinating disease, which served as a useful model providing considerable insights into the pathogenesis of multiple sclerosis (MS). Mouse bone marrow mesenchymal stem cells (mBM-MSC) were shown to have neuroprotection capabilities in EAE. Resveratrol is a small polyphenolic compound and possess therapeutic activity in various immune-mediated diseases. ⋯ In vivo efficacy experiments showed that mBM-MSCs or resveratrol alone led to a significant reduction in clinical scores, and combined treatment resulted in even more prominent reduction. The combined treatment with mBM-MSCs and resveratrol enhanced the immunomodulatory effects, showing suppressed proinflammatory cytokines (IFN-γ, TNF-α) and increased anti-inflammatory cytokines (IL-4, IL-10). The combination of mBM-MSCs and resveratrol provides a novel potential experimental protocol for alleviating EAE symptoms.