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Vesicular GABA transporter (VGAT) is expressed in GABAergic and glycinergic neurons, and is responsible for vesicular storage and subsequent exocytosis of these inhibitory amino acids. In this study, we show that VGAT recognizes β‐alanine as a substrate. Proteoliposomes containing purified VGAT transport β‐alanine using Δψ but not ΔpH as a driving force. The Δψ‐driven β‐alanine uptake requires Cl?. VGAT also facilitates Cl? uptake in the presence of β‐alanine. A previously described VGAT mutant (Glu213Ala) that disrupts GABA and glycine transport similarly abrogates β‐alanine uptake. These findings indicated that VGAT transports β‐alanine through a mechanism similar to those for GABA and glycine, and functions as a vesicular β‐alanine transporter.
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Aurelijus Burokas Elena Martín‐García Javier Gutiérrez‐Cuesta Santiago Rojas José Raúl Herance Juan Domingo Gispert Miquel‐Ángel Serra Rafael Maldonado 《Journal of neurochemistry》2014,130(1):126-135
Chronic stress represents a major environmental risk factor for mood disorders in vulnerable individuals. The neurobiological mechanisms underlying these disorders involve serotonergic and endocannabinoid systems. In this study, we have investigated the relationships between these two neurochemical systems in emotional control using genetic and imaging tools. CB1 cannabinoid receptor knockout mice (KO) and wild‐type littermates (WT) were exposed to chronic restraint stress. Depressive‐like symptoms (anhedonia and helplessness) were produced by chronic stress exposure in WT mice. CB1 KO mice already showed these depressive‐like manifestations in non‐stress conditions and the same phenotype was observed after chronic restraint stress. Chronic stress similarly impaired long‐term memory in both genotypes. In addition, brain levels of serotonin transporter (5‐HTT) were assessed using positron emission tomography. Decreased brain 5‐HTT levels were revealed in CB1 KO mice under basal conditions, as well as in WT mice after chronic stress. Our results show that chronic restraint stress induced depressive‐like behavioral alterations and brain changes in 5‐HTT levels similarly to those revealed in CB1 KO mice in non‐stressed conditions. These results underline the relevance of chronic environmental stress on serotonergic and endocannabinoid transmission for the development of depressive symptoms.
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Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis 下载免费PDF全文
Zhen Yuan Lifeng Yang Baian Chen Ting Zhu Mohammad Farooque Hassan Xiaomin Yin Xiangmei Zhou Deming Zhao 《Journal of neurochemistry》2015,133(5):722-729
The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β‐state oligomers. Herein, we demonstrate that β‐state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full‐length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP‐induced neurotoxicity. We have characterized protein misfolding cyclic amplification‐induced monomer‐to‐oligomer conversion of PrP from three species using western blotting, circular dichroism, size‐exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β‐oligomers are toxic to primary mouse cortical neurons independent of the presence of PrPC in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer‐induced apoptosis via regulation of Bcl‐2, Bax, and caspase‐3 in both wild‐type and PrP?/? cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain.
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Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20‐APP transgenic and wild‐type mice 下载免费PDF全文
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Anne M. Nixon Mark D. Meadowcroft Elizabeth B. Neely Amanda M. Snyder Carson J. Purnell Justin Wright Regina Lamendella Wint Nandar Xuemei Huang James R. Connor 《Journal of neurochemistry》2018,145(4):299-311
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Ethanol stimulates the in vivo axonal movement of neuropeptide dense‐core vesicles in Drosophila motor neurons 下载免费PDF全文
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Amphetamine is a central nervous system psychostimulant with a high potential for abuse. Recent literature has shown that genetic and drug‐induced elevations in dopamine transporter (DAT) expression augment the neurochemical and behavioral potency of psychostimulant releasers. However, it remains to be determined if the well‐documented differences in DAT levels across striatal regions drive regionally distinct amphetamine effects within individuals. DAT levels and dopamine uptake rates have been shown to follow a gradient in the striatum, with the highest levels in the dorsal regions and lowest levels in the nucleus accumbens shell; thus, we hypothesized that amphetamine potency would follow this gradient. Using fast scan cyclic voltammetry in mouse brain slices, we examined DAT inhibition and changes in exocytotic dopamine release by amphetamine across four striatal regions (dorsal and ventral caudate‐putamen, nucleus accumbens core and shell). Consistent with our hypothesis, amphetamine effects at the DAT and on release decreased across regions from dorsal to ventral, and both measures of potency were highly correlated with dopamine uptake rates. Separate striatal subregions are involved in different aspects of motivated behaviors, such as goal‐directed and habitual behaviors, that become dysregulated by drug abuse, making it critically important to understand regional differences in drug potencies.
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《Journal of neurochemistry》2019,149(5):559-561
We are very sad that the ISN lost its President Kazuhiro Ikenaka, Professor and Chairman at National Institute for Physiological Sciences (NIPS), Director of Okazaki Institute of Integrative Biology. JNeurochem published an Obituary to value his outstanding achievements: Akio Wanaka et al. (2019) OBITUARY Kazuhiro Ikenaka (1952‐2018). https://doi.org/10.1111/jnc.14679
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Vitamin C modulates glutamate transport and NMDA receptor function in the retina 总被引:1,自引:0,他引:1 下载免费PDF全文
Ivan Domith Renato Socodato Camila C. Portugal Andressa F. Munis Aline T. Duarte‐Silva Roberto Paes‐de‐Carvalho 《Journal of neurochemistry》2018,144(4):408-420
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Female hypocretin knockout (Hcrt KO) mice have increased body weight despite decreased food intake compared to wild type (WT) mice. In order to understand the nature of the increased body weight, we carried out a detailed study of Hcrt KO and WT, male, and female mice. Female KO mice showed consistently higher body weight than WT mice, from 4 to 20 months (20–60%). Fat, muscle, and free fluid levels were all significantly higher in adult (7–9 months) as well as old (18–20 months) female KO mice compared to age‐matched WT mice. Old male KO mice showed significantly higher fat content (150%) compared to age‐matched WT mice, but no significant change in body weight. Respiratory quotient (?19%) and metabolic rates (?14%) were significantly lower in KO mice compared to WT mice, regardless of gender or age. Female KO mice had significantly higher serum leptin levels (191%) than WT mice at 18–20 months, but no difference between male mice were observed. Conversely, insulin resistance was significantly higher in both male (73%) and female (93%) KO mice compared to age‐ and sex‐matched WT mice. We conclude that absence of the Hcrt peptide has gender‐specific effects. In contrast, Hcrt‐ataxin mice and human narcoleptics, with loss of the whole Hcrt cell, show weight gain in both sexes.
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Fumito Naganuma Takeo Yoshikawa Tadaho Nakamura Tomomitsu Iida Ryuichi Harada Attayeb S. Mohsen Yamato Miura Kazuhiko Yanai 《Journal of neurochemistry》2014,129(4):591-601
Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma‐derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time‐ and dose‐dependent manner. Kinetics analysis suggested the involvement of low‐affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na+/Cl? dependent but was inhibited by decynium‐22, an inhibitor of low‐affinity monoamine transporters, which supported the importance of low‐affinity transporters. RT‐PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma‐derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene‐knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.
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Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [18F]‐FDOPA PET study 下载免费PDF全文
David R Bonsall Michelle Kokkinou Mattia Veronese Christopher Coello Lisa A. Wells Oliver D. Howes 《Journal of neurochemistry》2017,143(5):551-560
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A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies 下载免费PDF全文
Yannick Poitelon Vittoria Matafora Nicholas Silvestri Desirée Zambroni Claire McGarry Nora Serghany Thomas Rush Domenica Vizzuso Felipe A. Court Angela Bachi Lawrence Wrabetz Maria Laura Feltri 《Journal of neurochemistry》2018,145(3):245-257
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Cocaine‐ and amphetamine‐regulated transcript peptide in the nucleus accumbens shell inhibits cocaine‐induced locomotor sensitization to transient over‐expression of α‐Ca2+/calmodulin‐dependent protein kinase II 下载免费PDF全文
Lixia Xiong Qing Meng Xi Sun Xiangtong Lu Qiang Fu Qinghua Peng Jianhua Yang Ki‐Wan Oh Zhenzhen Hu 《Journal of neurochemistry》2018,146(3):289-303
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The role of S‐nitrosylation of kainate‐type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid 下载免费PDF全文
Linxiao Wang Yanyan Liu Rulan Lu Guoying Dong Xia Chen Wenwei Yun Xianju Zhou 《Journal of neurochemistry》2018,144(3):255-270
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The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis 下载免费PDF全文
Johannes M. Thalhammer Franziska Fröb Melanie Küspert Simone Reiprich Elli‐Anna Balta D. Chichung Lie Michael Wegner Elisabeth Sock 《Journal of neurochemistry》2018,146(3):251-268