中東における対流圏オゾンの長期変動とそれに含まれる化学、および対流圏オゾン衛星観測のフィージビリティ検討

要約のみTohoku University村田功課

中東における対流圏オゾンの長期変動とそれに含まれる化学、および対流圏オゾン衛星観測のフィージビリティ検討

要約のみTohoku University村田功課

Ginger (Zingiber Officinale Roscoe) Prevents Morphine-Induced Addictive Behaviors in Conditioned Place Preference Test in Rats

Background: Consumption of chronic morphine induces neuro-inflammation and addictive seeking behavior. Ginger (Zingiber Officinale Roscoe), a well-known spice plant, has been used traditionally in the treatment of a wide variety of ailments. It has been shown that ginger has anti-inflammatory, anti-oxidative and antinociceptive properties. However, its influences on morphine-induced addictive behaviors have not yet been clarified. Methods: For conditioning to the morphine, the male Wistar rats received morphine (12 mg/kg intraperitoneally or i.p.) for 6 consecutive days and treatment groups were given different doses of ginger (25, 50 and 100 mg/kg intragastrically or i.g.) 30 min before morphine injection. For investigating addictive seeking behavior, conditioned place preference test (CPP) was used. Findings: Our result demonstrated that injection of morphine for 6 days induces dependency to morphine and creates addictive seeking behavior and ginger (100 mg/kg) could decrease time spend in conditioning box (addictive seeking behavior). Conclusion: The data indicated that ginger extract has a potential anti-addictive property against chronic usage of morphine

Ginger Extract Reduces Chronic Morphine-Induced Neuroinflammation and Glial Activation in Nucleus Accumbens of Rats

Background: Chronic usage of morphine elicits the production of inflammatory factors by glial cells andinduces neuroinflammation. Ginger (Zingiber Officinale Roscoe) is a medicinal herb that has antiinflammatory properties. It has been reported that ginger shows anti-addictive effects against chronic usageof morphine; however, its influence on morphine-induced neuroinflammation has not yet been clarified.Methods: Morphine (12 mg/kg) was administrated intraperitoneally for 6 consecutive days. To evaluate theeffect of ginger on morphine-induced neuroinflammation, ginger extract (100 mg/kg) was given orally 30minutes before morphine. Glial fibrillary acidic protein (GFAP) and P38 mitogen-activated protein kinase(p38 MAPK) levels were assayed by immunoblotting in the rat nucleus accumbens (NAcc).Findings: The injection of chronic morphine increased the levels of proteins involved in neuroinflammation(p38 MAPK and GFAP) in NAcc. Furthermore, the levels of p38 MAPK and GFAP significantly returned tothe control levels by ginger extract.Conclusion: The results suggest that the ginger extract can reduce morphine-induced neuroinflammation in NAcc

Maternal Separation and the Risk of Drug Abuse in Later Life

Maternal separation (MS) is defined as the termination of the continuity of mother-child relationship after the relationship is established. Although MS and maternal deprivation are different in terms of their definitions, these two terms are usually used interchangeably. This review aims to investigate the effect of MS on drug intake in adulthood. It has been proved that animal models are helpful in evaluating the effects of MS on drug intake risk in adulthood. There are relatively acceptable studies in this field on some drugs such as morphine, ethanol, and cocaine. However, very few animal studies, or even no animal study, have been conducted on some other drugs. The majority of these studies have considered MS as a risk factor for drug intake in adulthood. Different mechanisms are proposed for this phenomenon. Brain reward pathways are one of the main exploratory pathways of this process. Despite the importance of the issue, no human study with a specific concentration on investigating the relationship between MS and drug abuse in later life was found. Causal studies are warranted on humans to investigate the effect of MS on drug intake in later life

Effects of Maternal Separation on Nicotine-Induced Conditioned Place Preference and Later Spatial Learning and Memory Function in Adolescent Male Rats

Background: Disturbances in maternal care have been associated with increased risk for drug abuse later in life. However, there has been little investigation of the effects of maternal separation (MS), a model of early life stress, on nicotine dependence, specifically during adolescence. In the present study, we aimed to investigate the effect of MS on nicotine-conditioned place preference (CPP) in adolescent male rats. We also examined the impact of nicotine on spatial learning and memory impairments induced by MS.Methods: Rat pups were exposed to daily MS for 15 (MS15) or 180 (MS180) minutes during the first 2 weeks of life or reared under normal animal facility rearing (AFR) conditions. In postnatal day (PND) 28-34, they were conditioned with nicotine [0.6 mg/kg, subcutaneously (SC)] or saline and tested for preference over a period of 6 conditioning trials. Morris water maze (MWM) testing was performed to assess spatial cognitive function.Findings: The MS procedure used in our study failed to affect nicotine reward as measured by CPP in the adolescent male rats. Notably, significant spatial learning deficit was seen in the MS180 rats compared to those in the AFR and MS15 groups and nicotine administration modified the MS-induced learning defect in adolescent male rats.Conclusion: In conclusion, although MS revealed no influence on the sensitivity to the nicotine's reinforcing effects in adolescent male rats, the simultaneous effect of MS on learning performance may be altered by nicotine intake

Abscisic acid interplays with PPARγ receptors and ameliorates diabetes-induced cognitive deficits in rats

Objective: This study intended to evaluate if central administration of abscisic acid (ABA) alone or in combination with GW9662, a peroxisome proliferator–activated receptor γ (PPAR-γ) antagonist, could modulate learning and memory as well as hippocampal synaptic plasticity in a rat model of streptozotocin (STZ)–induced diabetes. Materials and Methods: Intraperitoneal injection of STZ (65 mg/kg) was used to induce diabetes. Diabetic rats were than treated with intracerebroventricular (i.c.v.) administration of ABA (10, 15 and 20 µg/rat), GW9662 (3 µg/rat) or GW9662 (3 µg/rat) plus ABA (20 µg/rat).Animals’ spatial and passive avoidance learning and memory performances were assessed by Morris water maze (MWM) and shuttle box tasks, respectively. Further, in vivo electrophysiological field recordings were assessed in the CA1 region. Results: STZ diabetic rats showed diminished learning and memory in both MWM and shuttle box tasks.  The STZ-induced memory deficits were attenuated by central infusion of ABA (10 and 20 µg/rat). Besides, STZ injection impaired long-term potentiation induction in CA1 neurons that was attenuated by ABA at 20 μg/rat. Central administration of GW9662 (3 µg/rat) alone did not modify STZ-induced spatial and passive avoidance learning and memory performances of rats. Further, GW9662 prevented ABA capacity to restore learning and memory in behavioral and electrophysiology trials. Conclusion: Altogether, ABA ameliorates cognitive deficits in rats via activation of PPAR-γ receptor in diabetic rats

Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection

Phosphoinositide-3-kinase (PI3K) is an enzyme group, known to regulate key survival pathways in acute myeloid leukaemia (AML). It generates phosphatidylinositol-3,4,5-triphosphate, which provides a membrane docking site for protein kinaseB activation. PI3K catalytic p110 subunits are divided into 4 isoforms; α,β,δ and γ. The PI3Kδ isoform is always expressed in AML cells, whereas the frequency of PI3Kγ expression is highly variable. The functions of these individual catalytic enzymes have not been fully resolved in AML, therefore using the PI3K p110δ and p110γ-targeted inhibitor IPI-145 (duvelisib) and specific p110δ and p110γ shRNA, we analysed the role of these two p110 subunits in human AML blast survival. The results show that PI3Kδ and PI3Kγ inhibition with IPI-145 has anti-proliferative activity in primary AML cells by inhibiting the activity of AKT and MAPK. Pre-treatment of AML cells with IPI-145 inhibits both adhesion and migration of AML blasts to bone marrow stromal cells. Using shRNA targeted to the individual isoforms we demonstrated that p110δ-knockdown had a more significant anti-proliferative effect on AML cells, whereas targeting p110γ-knockdown significantly inhibited AML migration. The results demonstrate that targeting both PI3Kδ and PI3Kγ to inhibit AML-BMSC interactions provides a biologic rationale for the pre-clinical evaluation of IPI-145 in AML

Effects of electrical stimulation of dorsal raphe nucleus on neuronal response properties of barrel cortex layer IV neurons following long-term sensory deprivation

Abstract: Objective To evaluate the effect of electrical stimulation of dorsal raphe nucleus (DRN) on response properties of layer IV barrel cortex neurons following long-term sensory deprivation. Methods: Male Wistar rats were divided into sensory-deprived (SD) and control (unplucked) groups. In SD group, all vibrissae except the D2 vibrissa were plucked on postnatal day one, and kept plucked for a period of 60 d. After that, whisker regrowth was allowed for 8-10 d. The D2 principal whisker (PW) and the D1 adjacent whisker (AW) were either deflected singly or both deflected in a serial order that the AW was deflected 20 ms before PW deflection for assessing lateral inhibition, and neuronal responses were recorded from layer IV of the D2 barrel cortex. DRN was electrically stimulated at inter-stimulus intervals (ISIs) ranging from 0 to 800 ms before whisker deflection. Results: PW-evoked responses increased in the SD group with DRN electrical stimulation at ISIs of 50 ms and 100 ms, whereas AW-evoked responses increased at ISI of 800 ms in both groups. Whisker plucking before DRN stimulation could enhance the responsiveness of barrel cortex neurons to PW deflection and decrease the responsiveness to AW deflection. DRN electrical stimulation significantly reduced this difference only in PW-evoked responses between groups. Besides, no DRN stimulation-related changes in response latency were observed following PW or AW deflection in either group. Moreover, condition test (CT) ratio increased in SD rats, while DRN stimulation did not affect the CT ratio in either group. There was no obvious change in 5-HT2A receptor protein density in barrel cortex between SD and control groups. Conclusion: These results suggest that DRN electrical stimulation can modulate information processing in the SD barrel cortex