Adverse prenatal environment, such as intrauterine growth retardation (IUGR), increases the risk for negative neurobehavioral outcomes. IUGR, affecting approximately 10% of all US infants, is a known risk factor for ADHD, schizophrenia spectrum disorders and addiction. Mouse dams were fed a protein deficient (8.5% protein) or isocaloric control (18% protein) diet through pregnancy and lactation (a well validated rodent model of IUGR). Dopamine-related gene expression, dopamine content and behavior were examined in adult offspring. IUGR offspring have 6-8 fold overexpression of dopamine (DA)-related genes (tyrosine hydroxylase (TH) and dopamine transporter) in brain regions related to reward processing (ventral tegmental area (VTA), nucleus accumbens, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURE/CONFLICTS OF INTERESTZ Vucetic, K Totoki, H. Schoch, KW Whitaker, T. E. Hill-Smith, and TM Reyes declare no conflicts of interest, either financial or otherwise. Irwin Lucki has been on the Scientific Advisory Board for Wyeth and has received research support from AstraZeneca, Wyeth, Forest and Epix pharmaceutical companies during the past 3 years. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 June 30. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript prefrontal cortex (PFC)) and homeostatic control (hypothalamus), as well as increased number of TH-ir neurons in the VTA and increased dopamine in the PFC. Cyclin-dependent kinase inhibitor 1C (Cdkn1c) is critical for dopaminergic neuron development. Methylation of the promoter region of Cdkn1c was decreased by half and there was a resultant 2-7 fold increase in Cdkn1c mRNA expression across brain regions. IUGR animals demonstrated alterations in dopamine-dependent behaviors, including altered reward-processing, hyperactivity and exaggerated locomotor response to cocaine.These data describe significant dopamine-related molecular and behavioral abnormalities in a mouse model of IUGR. This animal model, with both face validity (behavior) and construct validity (link to IUGR and dopamine dysfunction) may prove useful in identifying underlying mechanisms linking IUGR and adverse neurobehavioral outcomes such as ADHD. Keywordsdopamine; neurodevelopmental programming; epigenetics; addiction; perinatal nutrition A suboptimal prenatal environment, typically indicated by low birth weight or being small for gestational age (SGA), can increase the risk for adverse neurobehavioral outcomes, including ADHD (Hultman et al., 2007;Lahti et al., 2006), schizophr...
Electroencephalography (EEG) holds promise as a neuroimaging technology that can be used to understand how the human brain functions in real-world, operational settings while individuals move freely in perceptually-rich environments. In recent years, several EEG systems have been developed that aim to increase the usability of the neuroimaging technology in real-world settings. Here, the usability of three wireless EEG systems from different companies are compared to a conventional wired EEG system, BioSemi's ActiveTwo, which serves as an established laboratory-grade 'gold standard' baseline. The wireless systems compared include Advanced Brain Monitoring's B-Alert X10, Emotiv Systems' EPOC and the 2009 version of QUASAR's Dry Sensor Interface 10-20. The design of each wireless system is discussed in relation to its impact on the system's usability as a potential real-world neuroimaging system. Evaluations are based on having participants complete a series of cognitive tasks while wearing each of the EEG acquisition systems. This report focuses on the system design, usability factors and participant comfort issues that arise during the experimental sessions. In particular, the EEG systems are assessed on five design elements: adaptability of the system for differing head sizes, subject comfort and preference, variance in scalp locations for the recording electrodes, stability of the electrical connection between the scalp and electrode, and timing integration between the EEG system, the stimulus presentation computer and other external events.
Stroke is the leading cause of disability in adults. Drug treatments that target stroke-induced pathological mechanisms and promote recovery are desperately needed. In the brain, an ischemic event triggers major inflammatory responses that are mediated by the resident microglial cells. In this review, we focus on the microglia activation after ischemic brain injury as a target of immunomodulatory therapeutics. We divide the microglia-mediated events following ischemic stroke into three categories: acute, subacute, and long-term events. This division encompasses the spatial and temporal dynamics of microglia as they participate in the pathophysiological changes that contribute to the symptoms and sequela of a stroke. The importance of Toll-like receptor (TLR) signaling in the outcomes of these pathophysiological changes is highlighted. Increasing evidence shows that microglia have a complex role in stroke pathophysiology and they mediate both detrimental and beneficial effects on stroke outcome. So far, most of the pharmacological studies in experimental models of stroke have focused on neuroprotective strategies which are impractical for clinical applications. Post-ischemic inflammation is long lasting and thus, could provide a therapeutic target for novel delayed drug treatment. However, more studies are needed to elucidate the role of microglia in the recovery process from an ischemic stroke and to evaluate the therapeutic potential of modulating post-ischemic inflammation to promote functional recovery.
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