Collaborative Innovation Center for Brain Science
Collaborative Innovation Center for Brain Science
Hou X.-Y.,Huazhong University of Science and Technology |
Hu Z.-L.,Huazhong University of Science and Technology |
Hu Z.-L.,Key Laboratory of Neurological Diseases HUST |
Zhang D.-Z.,Huazhong University of Science and Technology |
And 16 more authors.
Antioxidants and Redox Signaling | Year: 2017
Aims: We asked whether hydrogen sulfide (H2S), as the third gaseous mediator, provided fast antidepressant effect on major depressive disorders and underlying mechanisms. Results: The decreased level of H2S was detected in the hippocampus of chronic unpredictable mild stress (CUMS)-treated rats. Acute administration of H2S either by H2S inhalation or by the donor NaHS produced a rapid antidepressant-like behavioral effect. Further investigation demonstrated that this effect of H2S was mediated by reversing the CUMS-induced decrease in dendritic spine density and required the activation of mammalian target of rapamycin (mTOR)C1 and neurotrophic TrkB receptors, which proceeded to increase synaptic protein expression, including postsynaptic density protein 95, synaptophysin, and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor GluR1/2 subunit. Innovation: This study provides the first direct evidence for detecting the decreased H2S in hippocampus of CUMS rats and the biological significance of H2S in treating major depression. Conclusion: Our data demonstrate that H2S activates mTORC1 signaling cascades and thereby produces fast-onset antidepressant effect. The study provides a profound insight into H2S or its donors as potent preventive and therapeutic agents for intervention of depression. Antioxid. Redox Signal. 27, 472-488. © 2017, Mary Ann Liebert, Inc.
Fan K.,Central South University |
Tang B.-S.,Central South University |
Tang B.-S.,State Key Laboratory of Medical Genetics |
Tang B.-S.,Collaborative Innovation Center for Brain Science |
And 9 more authors.
Neuroscience Letters | Year: 2016
Parkinson's disease (PD) is known as the most common neurodegenerative disease after Alzheimer's disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients. Recently, there are growing evidences indicating that patients with PD and AD share similarities in clinical features, pathology and genetic risks. However, no study has been conducted on the relations between AD associated genes and age at onset (AAO) of PD. In this study, we have detected 14 single nucleotide polymorphisms (SNPs) in 9 AD genome wide association studies top hit genes and 4 SNPs in 4 PD-cognitive impairment related genes among 297 Chinese PD patients. Through the linear regression analysis, we identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. This is the first report of significant associations of DYRK1A and MS4A6A SNPs and the AAO of PD. On account of their effects both in AD and PD, it is indicated that AD and PD possibly share some common pathways. © 2016 Elsevier Ireland Ltd.
Tang Y.,Central South University |
Meng L.,Central South University |
Wan C.-M.,Central South University |
Liu Z.-H.,Central South University |
And 8 more authors.
Neuroscience Letters | Year: 2017
Parkinson's disease (PD) is a chronic, progressive, and degenerative neurological disorder that is characterized by the degeneration of dopamine neurons in the substantia nigra and the formation of intracellular Lewy inclusion bodies. Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to determine whether the presence of PD could be “predicted” based on resting fluctuations in the blood oxygenation level dependent signal. We utilized RS-fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and the fractional ALFF (fALFF) in 51 patients with PD and 50 age- and sex-matched healthy controls. Compared with the healthy controls, the individuals with PD exhibited altered ALFFs in the bilateral lingual gyrus and left putamen and an altered fALFF in the right cerebellum posterior lobe. Support vector machines (SVMs), which comprise a supervised pattern recognition method that enables predictions at the individual level, were trained to separate individuals with PD from healthy controls based on the ALFF and fALFF. Using the leave-one-out cross-validation method to analyze our sample, we reliably distinguished the participants with PD from the controls with 92% sensitivity and 87% specificity. Overall, these findings suggest that the SVM-neuroimaging approach may be of particular clinical value because it enables the accurate identification of PD at the individual level. RS-fMRI should be considered for development as a biomarker and an analytical tool for the evaluation of PD. © 2017 Elsevier B.V.
Yang Y.,Collaborative Innovation Center for Brain Science |
Wang Z.-H.,Collaborative Innovation Center for Brain Science |
Jin S.,CAS Wuhan Institute of Physics and Mathematics |
Gao D.,Collaborative Innovation Center for Brain Science |
And 19 more authors.
Nature Communications | Year: 2016
Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF-and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.
Yao Y.,Fudan University |
Yao Y.,Collaborative Innovation Center for Brain Science |
Cui X.,Collaborative Innovation Center for Brain Science |
Al-Ramahi I.,Baylor College of Medicine |
And 12 more authors.
eLife | Year: 2015
Huntington's disease (HD) represents an important model for neurodegenerative disorders and proteinopathies. It is mainly caused by cytotoxicity of the mutant huntingtin protein (Htt) with an expanded polyQ stretch. While Htt is ubiquitously expressed, HD is characterized by selective neurodegeneration of the striatum. Here we report a striatal-enriched orphan G protein-coupled receptor(GPCR) Gpr52 as a stabilizer of Htt in vitro and in vivo. Gpr52 modulates Htt via cAMP-dependent but PKA independent mechanisms. Gpr52 is located within an intron of Rabgap1l, which exhibits epistatic effects on Gpr52-mediated modulation of Htt levels by inhibiting its substrate Rab39B, which co-localizes with Htt and translocates Htt to the endoplasmic reticulum. Finally, reducing Gpr52 suppresses HD phenotypes in both patient iPS-derived neurons and in vivo Drosophila HD models. Thus, our discovery reveals modulation of Htt levels by a striatal-enriched GPCR via its GPCR function, providing insights into the selective neurodegeneration and potential treatment strategies. © 2015, eLife Sciences Publications Ltd. All Rights Reserved