International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
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Int. J. Dev. Neurosci. · Dec 2013
Social communication mediates the relationship between emotion perception and externalizing behaviors in young adult survivors of pediatric traumatic brain injury (TBI).
Traumatic brain injury (TBI) is a common cause of childhood disability, and is associated with elevated risk for long-term social impairment. Though social (pragmatic) communication deficits may be among the most debilitating consequences of childhood TBI, few studies have examined very long-term communication outcomes as children with TBI make the transition to young adulthood. In addition, the extent to which reduced social function contributes to externalizing behaviors in survivors of childhood TBI remains poorly understood. ⋯ Compared to controls the TBI group had significantly greater social communication difficulty, which was associated with more frequent externalizing behaviors and poorer emotion perception. Analyses demonstrated that reduced social communication mediated the association between poorer emotion perception and more frequent externalizing behaviors. Our findings indicate that socio-cognitive impairments may indirectly increase the risk for externalizing behaviors among young adult survivors of childhood TBI, and underscore the need for targeted social skills interventions delivered soon after injury, and into the very long-term.
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Int. J. Dev. Neurosci. · Dec 2013
Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats.
Prenatal exposure to moderate doses of valproic acid (VPA) produces brainstem abnormalities, while higher doses of this teratogen elicit social deficits in the rat. In this pilot study, we examined effects of prenatal exposure to a moderate dose of VPA on behavior and on transcriptomic expression in three brain regions that mediate social behavior. Pregnant Long Evans rats were injected with 350 mg/kg VPA or saline on gestational day 13. ⋯ A common feature among the proteins encoded by the dysregulated genes was their ability to be modulated by acetylation. Analysis of the expression of individual exons also revealed that genes involved in post-translational modification and epigenetic regulation had particular isoforms that were ubiquitously dysregulated across brain regions. The vulnerability of these genes to the epigenetic effects of VPA may highlight potential mechanisms by which prenatal VPA exposure alters the development of social behavior.
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Int. J. Dev. Neurosci. · Nov 2013
ReviewOligodendrogenesis from neural stem cells: perspectives for remyelinating strategies.
Mobilization of remyelinating cells spontaneously occurs in the adult brain. These cellular resources are specially active after demyelinating episodes in early phases of multiple sclerosis (MS). Indeed, oligodendrocyte precursor cells (OPCs) actively proliferate, migrate to and repopulate the lesioned areas. ⋯ Thus, much effort has been focused on finding molecular targets that drive oligodendrocytes commitment and development. The present review explores several aspects of remyelination that must be considered in the design of a cell-based therapy for MS, and explores more deeply the challenge of fostering oligodendrogenesis. In this regard, we discuss herein a tool developed in our research group useful to search novel oligodendrogenic factors and to study oligodendrocyte differentiation in a time- and cost-saving manner.
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Int. J. Dev. Neurosci. · Oct 2013
ReviewShaping synaptic plasticity: the role of activity-mediated epigenetic regulation on gene transcription.
Learning and memory are basic functions of the brain that allowed human evolution. It is well accepted that during learning and memory formation the dynamic establishment of new active synaptic connections is crucial. Persistent synaptic activation leads to molecular events that include increased release of neurotransmitters, increased expression of receptors on the postsynaptic neuron, thus creating a positive feedback that results in the activation of distinct signaling pathways that temporally and permanently alter specific patterns of gene expression. ⋯ Even less is known regarding the signaling events triggered by synaptic activity that regulate these epigenetic marks. Here we review the current understanding of the molecular mechanisms controlling activity-dependent gene transcription leading synaptic plasticity and memory formation. We describe how Ca(2+) entry through N-methyl-d-aspartate-type glutamate neurotransmitter receptors result in the activation of specific signaling pathways leading to changes in gene expression, giving special emphasis to the recent data pointing out different epigenetic mechanisms (histone acetylation, methylation and phosphorylation as well as DNA methylation and hydroxymethylation) underlying learning and memory.
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Int. J. Dev. Neurosci. · Oct 2013
HDAC inhibitors dysregulate neural stem cell activity in the postnatal mouse brain.
The mammalian central nervous system (CNS) undergoes significant expansion postnatally, producing astrocytes, oligodendrocytes and inhibitory neurons to modulate the activity of neural circuits. This is coincident in humans with the emergence of pediatric epilepsy, a condition commonly treated with valproate/valproic acid (VPA), a potent inhibitor of histone deacetylases (HDACs). The sequential activity of specific HDACs, however, may be essential for the differentiation of distinct subpopulations of neurons and glia. ⋯ By one month after VPA, OB interneuron genesis was significantly and differentially reduced in both periglomerular and granule neurons. Using neurosphere assays to test if VPA directly regulates NSC activity, we found that short term treatment with VPA in vivo reduced neurosphere numbers and size, a phenotype that was also obtained in neurospheres from control mice treated with VPA and an alternative HDAC inhibitor, Trichostatin A (TSA) at 0 and 3 days in vitro (DIV). Collectively, these data show that clinically used HDAC inhibitors like VPA and TSA can perturb postnatal neurogenesis; and their use should be carefully considered, especially in individuals whose brains are actively undergoing key postnatal time windows of development.