Neuroreport
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Re-exposure to morphine-associated environments elicits morphine-seeking behavior after a long period of withdrawal in rats with a history of morphine dependence. Adaptations in glutamate receptor 1 (GluR1) phosphorylation in limbic brain regions have been shown to occur during withdrawal from addictive drugs, such as cocaine, methamphetamine, and heroin. However, whether similar adaptations exist after spontaneous withdrawal from repeated morphine intake has not been studied. ⋯ Phosphorylation of GluR1 at Ser845, but not Ser831, increases in the nucleus accumbens and central amygdala from 1 to 10 days of withdrawal, and there were no changes in GluR1 phosphorylation at Ser845 or Ser831 in the hippocampal CA1 subregion from 1 to 10 days of withdrawal. Significant positive correlations between numbers of drug-seeking responses and GluR1 phosphorylation at Ser845 in the nucleus accumbens were found in individual animals. These results suggest that time-dependent and region-specific changes in phosphorylation of GluR1 at Ser845, but not Ser831, are involved in the drug-seeking behavior elicited by re-exposure to the morphine-associated context.
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Transient global ischemia induces selective hippocampal pyramidal neuronal death. Under conditions of severe ischemic hypoxia, hypoxia-inducible factor-1α (HIF-1α) induces apoptosis. Exendin-4 (Ex-4), the glucagon-like peptide-1 receptor (GLP-1R) agonist, provides neuroprotection against brain damage after cerebral ischemia. ⋯ These in-vivo results were confirmed in vitro in SH-SY5Y cells and primary cortical neurons treated with 100 nM of Ex-4 under hypoxic conditions (0.1%>O2). We found that Ex-4 decreased the HIF-1α expression in the SH-SY5Y cell line and primary cortical neurons under hypoxic conditions, and this effect was reversed by cotreatment with exendin (9-39), a GLP-1R antagonist. These results suggest that HIF-1α may be involved in the neuroprotective effect of Ex-4 in the hypoxia-damaged brain.
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Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow-Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo. The results clearly indicate that water influx into the CSF is regulated by AQP-4, and not by AQP-1, strongly supporting the Oreskovic and Klarica hypothesis.
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Intrastriatal transplantation of dopamine (DA) neurons can restore DA levels in the striatum and improve parkinsonian deficits in experimental studies. However, the mechanisms underlying these effects are poorly understood. Corticostriatal synaptic plasticity represents an important cellular mechanism for information storage and behavioural learning in the brain. ⋯ In turn, malfunctioning synaptic plasticity is associated with motor deficits that resemble features of PD. It is yet unknown whether or not transplanted dopaminergic neurons can restore these striatal deficits in PD. Could this be the mechanism underlying the therapeutic effects of transplants? Recent studies have begun to shed light on this matter using different approaches.
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The aim of this study was to investigate the expression of total calcium/calmodulin-dependent protein kinase II (CaMKII) and its phosphorylated α isoform in the dorsal horn of the spinal cord in an animal model of long-term diabetes. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin, and expression of total CaMKII, the phosphorylated α-CaMKII isoform, and isolectin B4 was analyzed by immunohistochemical analysis in the dorsal horn of the spinal cord 6 and 12 months after diabetes induction. Results were compared with those for control rats of the same age. ⋯ The expression of activated α-CaMKII 12 months after diabetes induction was most pronounced in laminae I-VI of the dorsal horn, not corresponding with the highest expression of isolectin B4 in laminae I-III. Increased expression of CaMKII in the dorsal horn during long-term diabetes could be involved in the development of neuropathic symptoms in diabetes. The expression pattern of CaMKII during long-term diabetes indicates that it affects the entire sensory input.