Neuroscience
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Injury to the cerebellum and brainstem is becoming increasingly recognized in prematurely born infants. The role of infection/inflammation in mediating damage to those structures in the preterm brain is largely unknown. Preterm fetal sheep (70% gestation) received either saline-vehicle (control group; n=11) or Escherichia coli lipopolysaccharide (100 ng intravenous [i.v.]; lipopolysaccharide [LPS] group; n=9), and were allowed to recover for 3 days before sacrifice. ⋯ Ionized calcium binding adapter molecule 1 (Iba1)-positive cells which had the morphology of activated microglia were commonly observed in areas of injury. There was no obvious injury to the cerebellar cortex or to cerebellar Purkinje cells, and no obvious injury in any region of the brainstem. These data provide support for a role of infection/inflammation in selective white matter injury in the immature cerebellum, and demonstrate a differential vulnerability of the brainstem and cerebellar white matter to injury at this time.
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Recent studies have suggested that docosahexaenoic acid (DHA) enhances neuronal differentiation of neural stem cells (NSCs) isolated from rat embryonic day 14.5. However the underlying mechanism remains largely unknown. ⋯ In this study, we show that treatment with DHA under differentiation conditions without basic fibroblast growth factor, (1) increases Tuj-1 and MAP2 positive cells in NSCs, (2) that the expression level of Hes1 mRNA and protein decreased significantly from day 1 to day 4, on the other hand, the NeuroD mRNA expression level increased from day 1 to day 4 after treatment with DHA and (3) decreased the percentage of S-phase cells, which correlated with prolonged expression of cyclin-dependent kinase inhibitor p27(kip1), suggesting that DHA enhances neuronal differentiation of NSCs, in part, by controlling the bHLH transcription factors and promoting cell cycle exit. We therefore speculate that DHA is one of the essential key molecules for neuronal differentiation of NSCs.
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Maternal heroin abuse has been shown to result in teratogenic neurobehavioral defects in the offspring, but the underlying mechanisms remain largely unknown. This study was designed to explore the role of neuronal apoptosis in the heroin-induced neurobehavioral defects of learning and memory. Pregnant BALB/c mice were treated with either heroin or saline. ⋯ The results also showed that the mRNA and protein expressions of caspase-3 and Bax were significantly increased, while that of Bcl-2 was markedly decreased in the HER group compared with both the SAL and CON groups. The immunohistochemistry revealed significant caspase-3 immunoreactivity in the dentate gyrus and cornu ammonis (CA) 1 subareas of the hippocampal formation, whereas, no significant changes were seen in subarea CA3. These findings suggest that prenatal heroin exposure during the E9-18 period enhances neuronal apoptosis by altering the expressions of caspase-3, Bcl-2, and Bax in the mouse hippocampus, and leads to impairment in hippocampus-dependent learning and memory.
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Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. ⋯ Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior.
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Four experiments examined the disruptive effects of selective lesions in limbic thalamic nuclei on retrosplenial cortex function, as characterized by striking changes in immediate-early gene activity. Major goals were to test the specificity of these retrosplenial changes, to define better their time course, and to assess the spread of retrosplenial dysfunction with time post-surgery. Experiment 1 examined the activity of two immediate-early genes (c-Fos, Zif268) in the retrosplenial cortex after unilateral anterior thalamic nuclei lesions (1, 2, or 8 weeks post-surgery). ⋯ Associated, subtle changes to cell morphometry (size and sphericity) were found in the retrosplenial cortex. In contrast, unilateral lesions in the adjacent laterodorsal thalamic nucleus (Experiment 4) did not significantly alter retrosplenial cortex c-Fos activity, so highlighting the anatomical specificity of the anterior thalamic lesion effects. These findings not only indicate that the impact of anterior thalamic lesions on cognition could be enhanced by retrosplenial cortex dysfunction but they also show that the effects could increase with longer post-insult survival.