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1.
Inorg Chem ; 58(19): 13102-13107, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31502447

RESUMO

A face-centered-cubic (FCC) YH3 phase is known to be stable only under high pressure (HP) of more than gigapascal order, and it reverts to the hexagonal YH3 ambient-pressure phase when the pressure is released. We previously found that the FCC YH3 can be stabilized even at ambient pressure by substituting Y for 10 mol % Li (LiH-stabilized YH3, LSY). The LSY was synthesized by heat treatment under gigapascal HP, but this process is unfavorable for mass production; that is, only a few tens of milligrams of a sample can be obtained in a single batch. In this study, we overcame this problem by applying a ball milling (BM) process for synthesizing the LSY phase, and the yield by the BM process reached on the order of grams. We confirmed that the structure of the BM sample was the same as that of the HP sample by X-ray diffractometry, Raman spectroscopy, and neutron total scattering pair distribution function analyses. The crystallinity of the BM sample, however, was lower than that of the HP sample. The difference in the crystallinity affects the thermal stability of the LSY. The BM sample with a lower crystallinity released hydrogen at a lower temperature. The BM sample was found to reversibly desorb/absorb hydrogen maintaining its initial FCC structure when the rehydrogenation temperature was at 423 K. However, when the rehydrogenation temperature of BM sample was more than 573 K, the FCC structure changed to the hexagonal ambient pressure phase due to thermal instability of FCC phase for the BM sample.

2.
J Med Case Rep ; 13(1): 207, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31279335

RESUMO

BACKGROUND: Little information is available on the treatment of open bite with temporomandibular joint disorder by intrusion of molars using miniscrews. CASE PRESENTATION: This case report describes a 42-year-old Japanese woman with a skeletal class II severe anterior open bite and temporomandibular joint disorder. The pretreatment magnetic resonance imaging of both temporomandibular joints revealed osteoarthritis and anterior disc displacement without reduction in both temporomandibular joints. A stabilization splint was used before orthodontic treatment and bilateral upper and lower premolars were extracted. Miniscrews were inserted into the palatal region to intrude the maxillary molars and avoid loss of anchorage. The maxillary left first molar was also extracted to improve the molar relationship and the dental midline. Normal overjet and overbite with Angle class I molar relationship were achieved, and the upper and lower midlines coincided. Our patient's teeth continued to be stable and her temporomandibular joint was asymptomatic after a retention period of 2 years. CONCLUSIONS: Intrusion of molars by miniscrews is available for skeletal class II severe open bite.

3.
Nat Commun ; 10(1): 2578, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189877

RESUMO

Fast ionic conductors have considerable potential to enable technological development for energy storage and conversion. Hydride (H-) ions are a unique species because of their natural abundance, light mass, and large polarizability. Herein, we investigate characteristic H- conduction, i.e., fast ionic conduction controlled by a pre-exponential factor. Oxygen-doped LaH3 (LaH3-2xOx) has an optimum ionic conductivity of 2.6 × 10-2 S cm-1, which to the best of our knowledge is the highest H- conductivity reported to date at intermediate temperatures. With increasing oxygen content, the relatively high activation energy remains unchanged, whereas the pre-exponential factor decreases dramatically. This extraordinarily large pre-exponential factor is explained by introducing temperature-dependent enthalpy, derived from H- trapped by lanthanum ions bonded to oxygen ions. Consequently, light mass and large polarizability of H-, and the framework comprising densely packed H- in LaH3-2xOx are crucial factors that impose significant temperature dependence on the potential energy and implement characteristic fast H- conduction.

4.
Int J Neuropsychopharmacol ; 22(7): 449-452, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31135879

RESUMO

Although the N-methyl-D-aspartate receptor antagonist ketamine has attracted attention because of its rapid and sustained antidepressant effects in depressed patients, its side effects have raised some concerns. Ketamine is a racemic mixture of equal amounts of the enantiomers (R)-ketamine and (S)-ketamine. The neural mechanisms that underlie the differential effects of these enantiomers remain unclear. We investigated cognitive impairment that was induced by ketamine and its enantiomers in N-methyl-D-aspartate GluN2D receptor subunit knockout (GluN2D-KO) mice. In the novel object recognition test, (RS)-ketamine and (S)-ketamine caused cognitive impairment in both wild-type and GluN2D-KO mice, whereas (R)-ketamine induced such cognitive impairment only in wild-type mice. The present results suggest that the GluN2D subunit plays an important role in cognitive impairment that is induced by (R)-ketamine, whereas this subunit does not appear to be involved in cognitive impairment that is induced by (RS)-ketamine or (S)-ketamine.

5.
J Phys Chem B ; 123(23): 4967-4975, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31094512

RESUMO

Neutron diffraction measurements have been carried out on 10 mol % LiTFSA (TFSA: bis(trifluoromethylsulfonil)amide) solutions in methanol- d4 and 2-propanol- d8 to obtain information on the solvation structure of Li+. The detailed coordination structure of solvent molecules within the first solvation shell of Li+ was determined through the least-squares fitting analysis of the difference function between normalized scattering cross sections observed for 6Li/7Li isotopically substituted sample solutions. The nearest-neighbor Li+···O distance and coordination number determined for the 10 mol % LiTFSA-methanol- d4 solution are rLiO = 1.98 ± 0.02 Å and nLiO = 3.8 ± 0.6, respectively. In the 2-propanol- d8 solution, it has been revealed that 2-propanol- d8 molecules within the first solvation shell of Li+ take at least two different coordination geometries with the intermolecular nearest-neighbor Li+···O distance of rLiO = 1.93 ± 0.04 Å. The Li+···O coordination number, nLiO = 3.3 ± 0.3, is determined. Ion-pair formation in the LiTFSA-methanol and LiTFSA-2-propanol solutions has been investigated by the attenuated total reflection infrared spectroscopic method. Mole fractions of free, Li+-bound, and aggregated TFSA- are derived from the peak deconvolution analysis of vibrational bands observed for TFSA-.

6.
Nat Commun ; 10(1): 1567, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952864

RESUMO

Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in ß-oxidation following suppression of transactivation by PPARα. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARα to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARα activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARα activation upon fasting by promoting degradation of NCoR1 and thus regulates ß-oxidation and ketone bodies production.


Assuntos
Autofagia , Metabolismo dos Lipídeos , Correpressor 1 de Receptor Nuclear/metabolismo , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/fisiologia , Jejum , Corpos Cetônicos/metabolismo , Fígado/metabolismo , Camundongos , Correpressor 1 de Receptor Nuclear/fisiologia , Oxirredução , PPAR alfa
7.
Arch Oral Biol ; 102: 83-92, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978553

RESUMO

OBJECTIVE: The present study aimed to investigate the inhibitory effect of acetaminophen on apical root resorption during orthodontic tooth movement by controlling inflammation in the periodontal ligament and apical pulp tissue. METHODS: Human periodontal ligament and pulp cells were subjected to 10 kPa of cyclic tensile force (CTF) in a Flexcell Strain Unit for 48 h. Then, 10 and 100 µM acetaminophen were added to the culture medium, and the expression of interleukin (IL)-1B, receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)α, and colony stimulating factor 1 (CSF1) were evaluated. In an animal experiment, the upper first molars of 7-week-old rats were moved mesially by applying 10 g of orthodontic force. After 30 days of force application, the effects of acetaminophen on apical root resorption were examined. RESULTS: In both the periodontal ligament and pulp cells, the expression levels of IL-1B, TNFα, RANKL, and CSF1 were significantly higher in the CTF-treated group than in the control group. However, the expression levels of these factors were decreased by acetaminophen administration. High expression of IL-1B, TNFα, RANKL, and CSF1 at the root apex were also detected immunohistochemically in rats after tooth movement, but were decreased by acetaminophen administration. In addition, the number of odontoclasts and the amount of apical root resorption were significantly decreased in the acetaminophen group. Importantly, no significant difference in tooth movement was observed between the acetaminophen and control groups. CONCLUSIONS: These results suggest that acetaminophen can reduce severe root resorption in the apex area without disturbing orthodontic tooth movement.

8.
J Affect Disord ; 250: 419-424, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878654

RESUMO

BACKGROUND: It is clinically important to know who are likely to respond more or less to antidepressants. However, meaningful effect modifiers (variables associated with differential response depending on the treatment) are yet to be identified. METHODS: We conducted individual participant data (IPD) meta-analysis and meta-regression to explore effect modifiers in placebo-controlled antidepressant trials conducted so far in Japan. RESULTS: We obtained access to IPD from seven placebo-controlled trials comparing bupropion, duloxetine, escitalopram, mirtazapine, paroxetine or venlafaxine with placebo in the acute phase treatment of major depression (total n = 2803). The higher the guilt subscale score of the baseline Hamilton Rating Scale for Depression (HRSD), the greater the difference in reduction in depression severity between the antidepressants and placebo at week 6, while the older the current age or the age at onset, the smaller the difference. At week 8, the guilt subscale score of HRSD and presence of suicidal ideation at baseline predicted greater, and the anhedonia subscale and insomnia subscale scores of HRSD and early response at week 2 predicted smaller, difference in reduction. LIMITATIONS: Different studies measured different sets of baseline variables and we were able to analyze only a limited set of candidate variables for effect modification. CONCLUSION: Age, age at onset, several HRSD subscales including guilt, anhedonia and insomnia, presence of suicidal ideation at baseline and early response are potential effect modifiers for response to antidepressants in the acute phase antidepressant treatment of major depression. Future trials need to measure these and additional variables in concerted efforts to enable matching of treatments with individual characteristics in depression.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Bupropiona/uso terapêutico , Citalopram/uso terapêutico , Depressão/tratamento farmacológico , Método Duplo-Cego , Cloridrato de Duloxetina/uso terapêutico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Paroxetina/uso terapêutico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Cloridrato de Venlafaxina/uso terapêutico
9.
Neuropsychopharmacol Rep ; 39(2): 90-99, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30756527

RESUMO

AIMS: Pharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein-activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double-blind, placebo-controlled trial. METHODS: The recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4%® (ifenprodil tartrate). Follow-up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self-administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84-day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving. DISCUSSION: This study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off-label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence. TRIAL REGISTRY: This trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018).

10.
Transl Psychiatry ; 9(1): 85, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755587

RESUMO

Psychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Structures of cerebral tissues of the anterior cingulate cortex were visualized with synchrotron radiation nanotomography. Tissue constituents visualized in the three-dimensional images were traced to build Cartesian coordinate models of tissue constituents, such as neurons and blood vessels. The obtained Cartesian coordinates were used for calculating curvature and torsion of neurites in order to analyze their geometry. Results of the geometric analyses indicated that the curvature of neurites is significantly different between schizophrenia and control cases. The mean curvature of distal neurites of the schizophrenia cases was ~1.5 times higher than that of the controls. The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene, suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. It has been shown that the anterior cingulate cortex analyzed in this study has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia.

11.
J Am Chem Soc ; 141(8): 3376-3379, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30763079

RESUMO

LnNiSi (Ln = La-Nd) comprising a three-dimensional NiSi framework has electrons in the crystallographic cavity space. In the temperature region 473-773 K, it accepts the insertion/de-insertion of hydrogen topotactically without a change in unitcell volume. The insertion of hydrogens into the cavity space is accompanied by a redox reaction with the orbitals of atoms constituting the cavity wall. Having small work functions, such intermetallic electrides exhibit metallic electrical and magnetic properties. Owing to a high electron-donating power and reversible exchange between hydrogen and the electrons, Ru5wt%-loaded LaNiSi powder worked as an efficient catalyst for ammonia synthesis under ambient pressure.

12.
Life Sci Alliance ; 2(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30683688

RESUMO

Stimulator of interferon genes (STING) plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here, we show that costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.

13.
Mol Brain ; 12(1): 3, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621732

RESUMO

The mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cell metabolism, growth, and proliferation. The overactivation of mTOR has been implicated in the pathogenesis of syndromic autism spectrum disorder (ASD), such as tuberous sclerosis complex (TSC). Treatment with the mTOR inhibitor rapamycin improved social interaction deficits in mouse models of TSC. Prenatal exposure to valproic acid (VPA) increases the incidence of ASD. Rodent pups that are exposed to VPA in utero have been used as an animal model of ASD. Activation of the mTOR signaling pathway was recently observed in rodents that were exposed to VPA in utero, and rapamycin ameliorated social interaction deficits. The present study investigated the effect of rapamycin on social interaction deficits in both adolescence and adulthood, and gene expressions in mice that were exposed to VPA in utero. We subcutaneously injected 600 mg/kg VPA in pregnant mice on gestational day 12.5 and used the pups as a model of ASD. The pups were intraperitoneally injected with rapamycin or an equal volume of vehicle once daily for 2 consecutive days. The social interaction test was conducted in the offspring after the last rapamycin administration at 5-6 weeks of ages (adolescence) or 10-11 weeks of age (adulthood). Whole brains were collected after the social interaction test in the adulthood, and microarray and Western blot analyses were performed. Mice that were exposed to VPA and treated with vehicle exhibited a decrease in social interaction compared with control mice that were treated with vehicle. Rapamycin treatment in VPA-exposed mice improved social deficits. Mice that were exposed to VPA and treated with vehicle exhibited the aberrant expression of genes in the mTOR signaling pathway, and rapamycin treatment recovered changes in the expression of some genes, including Fyb and A330094K24Rik. Rapamycin treatment suppressed S6 phosphorylation in VPA-exposed mice. Aberrant gene expression was associated with social interaction deficits in VPA-exposed mice. Rapamycin may be an effective treatment for non-syndromic ASD in adolescent and adult patients who present impairments in the mTOR signaling pathway.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Relações Interpessoais , Efeitos Tardios da Exposição Pré-Natal/genética , Sirolimo/farmacologia , Ácido Valproico/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Proteína S6 Ribossômica/genética , Proteína S6 Ribossômica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
14.
Chemphyschem ; 20(10): 1392-1397, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30575253

RESUMO

The hydrogen-release reaction of a complex transition metal hydride, LaMg2 NiH7 , composed of La3+ , 2×Mg2+ , [NiH4 ]4- and 3×H- , was studied by thermal analyses, powder X-ray, and neutron diffraction and inelastic neutron scattering. Upon heating, LaMg2 NiH7 released hydrogen at approximately 567 K and decomposed into LaH2-3 and Mg2 Ni. Before the reaction, covalently bound hydrogen (Hc °v. ) in [NiH4 ]4- exhibited a larger atomic displacement than H- , although a weakening of the chemical bonds around [NiH4 ]4- and H- was observed. These results indicate the precursor phenomenon of a hydrogen-release reaction, wherein there is a large atomic displacement of Hc °v. that induces the hydrogen-release reaction rather than H- . As an isothermal reaction, LaMg2 NiH7 formed LaMg2 NiH2.4 at 503 K in vacuum for 48 h, and LaMg2 NiH2.4 reacted with hydrogen to reform LaMg2 NiH7 at 473 K under 1 MPa of H2 gas pressure for 10 h. These results revealed that LaMg2 NiH7 exhibited partially reversible hydrogen-release and uptake reactions.

15.
Mol Autism ; 9: 60, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498565

RESUMO

Background: Hyperserotonemia in the brain is suspected to be an endophenotype of autism spectrum disorder (ASD). Reducing serotonin levels in the brain through modulation of serotonin transporter function may improve ASD symptoms. Methods: We analyzed behavior and gene expression to unveil the causal mechanism of ASD-relevant social deficits using serotonin transporter (Sert) knockout mice. Results: Social deficits were observed in both heterozygous knockout mice (HZ) and homozygous knockout mice (KO), but increases in general anxiety were only observed in KO mice. Two weeks of dietary restriction of the serotonin precursor tryptophan ameliorated both brain hyperserotonemia and ASD-relevant social deficits in Sert HZ and KO mice. The expression of rather distinct sets of genes was altered in Sert HZ and KO mice, and a substantial portion of these genes was also affected by tryptophan depletion. Tryptophan depletion in Sert HZ and KO mice was associated with alterations in the expression of genes involved in signal transduction pathways initiated by changes in extracellular serotonin or melatonin, a derivative of serotonin. Only expression of the AU015836 gene was altered in both Sert HZ and KO mice. AU015836 expression and ASD-relevant social deficits normalized after dietary tryptophan restriction. Conclusions: These findings reveal a Sert gene dose-dependent effect on brain hyperserotonemia and related behavioral sequelae in ASD and a possible therapeutic target to normalize brain hyperserotonemia and ASD-relevant social deficits.

16.
Neuropsychopharmacol Rep ; 38(4): 175-181, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277654

RESUMO

AIM: Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health-related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness. METHODS: A total of 71 cancer patients rated their pain on an 11-point numerical rating scale twice before and after increasing opioid analgesics. A genomewide association study focusing on single nucleotide polymorphisms (SNPs) was conducted to associate pain decrease with increased dosage of opioid analgesics based on weight (ie, responsiveness to opioid analgesics). A genomewide significance (P < 5E-8) was set for multiplicity of analyses to control for false positives. RESULTS: Two SNPs passed the genomewide threshold for significance. One exonic SNP (rs1641025) was located in the ABAT [4-aminobutyrate aminotransaminase (GABA transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on chromosome 3, which was not associated with any known genes. These SNPs were not associated with opioid-related adverse effects. CONCLUSIONS: Our results preliminarily suggest that both SNPs might be potential candidate loci for responsiveness to opioid analgesics, and GABA transaminase might be a possible target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant pharmacotherapy. Our results should be validated in a large-scale study with a larger sample size.

17.
Biochem Biophys Res Commun ; 505(1): 81-86, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241938

RESUMO

Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.

18.
Neuropsychopharmacol Rep ; 38(3): 149-153, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30175528

RESUMO

AIM: Attention-deficit/hyperactivity disorder is a heterogeneous neurobiological disorder that is characterized by inattention, impulsivity, and an increase in motor activity. Although methylphenidate has been used as a medication for decades, unknown is whether methylphenidate treatment can cause drug dependence in patients with attention-deficit/hyperactivity disorder. This study investigated the reward-enhancing effects of methylphenidate using intracranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder, dopamine transporter knockout mice. METHODS: For the intracranial self-stimulation procedures, the mice were trained to nosepoke to receive direct electrical stimulation via an electrode that was implanted in the lateral hypothalamus. After the acquisition of nosepoke responding for intracranial self-stimulation, the effects of methylphenidate on intracranial self-stimulation were investigated. RESULTS: In the progressive-ratio procedure, dopamine transporter knockout mice exhibited an increase in intracranial self-stimulation compared with wild-type mice. Treatment with 5 and 10 mg/kg methylphenidate increased intracranial self-stimulation responding in wild-type mice. Methylphenidate at the same doses did not affect intracranial self-stimulation responding in dopamine transporter knockout mice. We then investigated the effects of high-dose methylphenidate (60 mg/kg) in a rate-frequency procedure. High-dose methylphenidate significantly decreased intracranial self-stimulation responding in both wild-type and dopamine transporter knockout mice. CONCLUSIONS: These results suggest that low-dose methylphenidate alters the reward system (ie, increases intracranial self-stimulation responding) in wild-type mice via dopamine transporter inhibition, whereas dopamine transporter knockout mice do not exhibit such alterations. High-dose methylphenidate appears to suppress intracranial self-stimulation responding not through dopamine transporter inhibition but rather through other mechanisms. These results support the possibility that methylphenidate treatment for attention-deficit/hyperactivity disorder does not increase the risk of drug dependence, in attention-deficit/hyperactivity disorder patients with dopamine transporter dysfunction.

19.
Inorg Chem ; 57(18): 11831-11838, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30178993

RESUMO

Hydrogenation of nonequilibrium alloys may form nanometer-sized metal hydride clusters, depending on the alloy compositions and hydrogenation conditions. Here in the Ti-rich compositions of the immiscible Mg-Ti system MgH2 clusters are embedded in a Ti-H matrix. Our previous works have indicated that the interface energy between the two metal hydrides reduces the stability of MgH2. The aim of our study is to obtain the structural information on the nanometer-sized clusters. Indeed, MgD2 clusters embedded in a face-centered-cubic (FCC) Ti-D matrix is found in Mg0.25Ti0.75D1.65 by means of 2H magic angle spinning nuclear magnetic resonance (MAS NMR). The atomic pair distribution function (PDF) analysis of neutron total scattering data suggests that the MgD2 clusters have an orthorhombic structure, which is different from a rutile-type body-centered-tetragonal (BCT) structure of α-MgD2 observed in the Mg-rich compositions. Our results suggest that we can tune the thermodynamics of hydrogen absorption and desorption in Mg-H using the interface energy effect and accompanying stress-induced structural change, which contributes to the substantial development of lightweight and inexpensive hydrogen storage materials.

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