International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
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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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Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and non-verbal communication, and repetitive behavior and restricted interests. The normal brain development during fetal brain development and the first year of life is critical to the behaviors and cognitions in adulthood. ⋯ It has been demonstrated a possible association between neural cell death and autism. Here, the abnormal apoptosis found in autism from postmortem and animal studies was reviewed and the possible mechanism was discussed.
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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 2011
ReviewErythropoietin for neonatal brain injury: opportunity and challenge.
Neonatal brain injury, caused by perinatal hypoxia-ischemia and extreme prematurity, remains a great challenge for prevention and treatment. There is no effective treatment for term hypoxic-ischemic encephalopathy (HIE) except hypothermia which by itself does not afford complete neuroprotection. ⋯ This review will focus on the possible mechanisms, recent clinical advances and potential complications of EPO used in research and the clinic. In addition, optimal dose and administrative routes of EPO, and novel EPO mimetics will be discussed.