Neuroscience
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The cerebellum contains more neurons than all other brain regions combined and these cells exhibit complex circuit development and dendritic elaboration during the postnatal period. Neural development, cellular morphogenesis, and synaptic plasticity are dependent on the dynamic regulation of the actin cytoskeleton by actin-binding proteins. The identification of the actin filament interactome, including proteins developmentally regulated in the postnatal cerebellum, could help define important regulators of actin cytoskeletal dynamics in developing cerebellar neurons. ⋯ As the result, nine genes encoding members of the cerebellar F-actin interactome were developmentally regulated in the transcriptional level and at least five of them exhibited a similar pattern at the protein expression level by Western blot analysis. Further fluorescent immunohistochemical observations demonstrated that the actin-associated proteins Lethal(2) giant larvae protein homolog 1 (LLGL1) and metastasis suppressor 1 (MTSS1) were specifically upregulated in granule neurons and Purkinje cells during morphogenesis of axons and dendrites. This work defines a provisional actin filament interactome in rat postnatal cerebellum and identifies several candidate proteins that may be involved in the postnatal development of the cerebellum.
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Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. ⋯ Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18β-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade.
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We have previously shown that ceftriaxone, β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1), reduced ethanol intake in alcohol-preferring (P) rats. GLT1 is a glial glutamate transporter that regulates the majority of extracellular glutamate uptake. We tested in this study the effects of neuroimmunophilin GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate), known also to upregulate GLT1 expression, in ethanol intake in P rats. ⋯ Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol naïve vehicle group. GPI-1046 (20mg/kg) increased GLT1 level in PFC compared to naïve control group that was exposed to water and food only. These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core.
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Nociceptive plasticity and central sensitization within the spinal cord depend on neurobiological mechanisms implicated in learning and memory in higher neural systems, suggesting that the factors that impact brain-mediated learning and memory could modulate how stimulation affects spinal systems. One such factor is temporal regularity (predictability). The present paper shows that intermittent hindleg shock has opposing effects in spinally transected rats depending upon whether shock is presented in a regular or irregular (variable) manner. ⋯ The effect of fixed-spaced stimulation lasted 24h. Treatment with fixed-spaced shock also attenuated the maintenance of capsaicin-induced EMR. The results show that variable intermittent shock enhances mechanical reactivity, while an extended exposure to fixed-spaced shock has the opposite effect on mechanical reactivity and attenuates capsaicin-induced EMR.
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Neural stem cells in the subventricular zone (SVZ) generate progenitors which in turn give rise to neuroblasts. These neuroblasts then migrate along the rostral migratory stream (RMS) in chains and reach the olfactory bulb (OB), where they mature into local interneurons. Interneurons in the OB are heterogeneous, which are mainly located in granular cell layer (GCL), external plexiform layer (EPL) and glomerular layer (GL). ⋯ These GFP+ neuroblasts of the 5HT3aR-BAC(EGFP) transgenic mouse migrate along the RMS to the OB where they differentiate into calretinin+ (CR+), parvabumin+ (PV+), vasoactive intestinal peptide+ (VIP+), somatostatin+ (Som+) and tyrosine hydroxylase+ (TH+), but not calbindin+ (CB+) interneurons. These GFP+ interneurons continuously express Sp8 in the OB. Furthermore, these results suggest that GFP-expressing cells are derived from LGE, and this transgenic mouse line will be a useful tool for studying the development and function of interneurons in both neocortex and OB.