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Ruinan Gu, Fali Zhang, Gang Chen, Chaojun Han, Jay Liu, Zhaoxiang Ren, Yi Zhu, John L Waddington, Long Tai Zheng, Xuechu Zhen
Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis...
October 18, 2016: Brain, Behavior, and Immunity
Chiung-Mei Chen, I-Cheng Chen, Ying-Lin Chen, Te-Hsien Lin, Wan-Ling Chen, Chih-Ying Chao, Yih-Ru Wu, Yeah-Ting Lu, Cheng-Yu Lee, Hong-Chi Chien, Ting-Shou Chen, Guey-Jen Lee-Chen, Chi-Mei Lee
BACKGROUND: The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. PURPOSE: We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP(+)-treated cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
October 11, 2016: Journal of Ethnopharmacology
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Jingjing He, Zheng Xiang, Xiaoqing Zhu, Zongyong Ai, Jingsong Shen, Tianzhuang Huang, Liegang Liu, Weizhi Ji, Tianqing Li
Parkinson's disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys...
October 12, 2016: Scientific Reports
Thomas I Talpalar, Adolfo E Talpalar
Hyperbaric environments induce the high pressure neurological syndrome (HPNS) characterized by hyperexcitability of the central nervous system (CNS) and memory impairment. Human divers and other animals experience the HPNS at pressures beyond 1.1 MPa. High pressure depresses synaptic transmission and alters its dynamics in various animal models. Medial perforant path (MPP) synapses connecting the medial entorhinal cortex with the hippocampal formation are suppressed by 50% at 10.1MPa. Reduction of synaptic inputs is paradoxically associated with enhanced ability of dentate gyrus (DG)' granule cells (GCs) to generate spikes at high pressure...
2016: Frontiers in Cellular Neuroscience
Mauricio P Cunha, Francis L Pazini, Vicente Lieberknecht, Josiane Budni, Ágatha Oliveira, Júlia M Rosa, Gianni Mancini, Leidiane Mazzardo, André R Colla, Marina C Leite, Adair R S Santos, Daniel F Martins, Andreza F de Bem, Carlos Alberto S Gonçalves, Marcelo Farina, Ana Lúcia S Rodrigues
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces motor and nonmotor dysfunctions resembling Parkinson's disease (PD); however, studies investigating the effects of 1-methyl-4-phenylpyridinium (MPP(+)), an active oxidative product of MPTP, are scarce. This study investigated the behavioral and striatal neurochemical changes (related to oxidative damage, glial markers, and neurotrophic factors) 24 h after intracerebroventricular administration of MPP(+) (1.8-18 μg/mouse) in C57BL6 mice...
October 8, 2016: Molecular Neurobiology
Meredith Meyer, Attila D Kovács, David A Pearce
Infantile CLN1 disease, also known as infantile neuronal ceroid lipofuscinosis, is a fatal childhood neurodegenerative disorder caused by mutations in the CLN1 gene. CLN1 encodes a soluble lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1), and it is still unclear why neurons are selectively vulnerable to the loss of PPT1 enzyme activity in infantile CLN1 disease. To examine the effects of PPT1 deficiency on several well-defined neuronal signaling and cell death pathways, different toxic insults were applied in cerebellar granule neuron cultures prepared from wild type (WT) and palmitoyl protein thioesterase 1-deficient (Ppt1 (-/-) ) mice, a model of infantile CLN1 disease...
October 8, 2016: Metabolic Brain Disease
Peizhou Jiang, Peng Huang, Shu-Hui Yen, Abba C Zubair, Dennis W Dickson
BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients...
October 6, 2016: Cytotherapy
Mrigendra Bir Karmacharya, Binika Hada, So Ra Park, Byung Hyune Choi
Many studies have shown that mitochondrial dysfunction and the subsequent oxidative stress caused by excessive reactive oxygen species (ROS) generation play a central role in the pathogenesis of Parkinson's disease (PD). We have previously shown that low-intensity ultrasound (LIUS) could reduce ROS generation by L-buthionine-(S,R)-sulfoximine (BSO) in retinal pigment epithelial cells. In this study, we studied the effects of LIUS stimulation on the ROS-dependent α-synuclein aggregation in 1-methyl-4-phenylpyridinium ion (MPP(+))-treated PC12 cells...
October 6, 2016: Molecular Neurobiology
Xue Li, Xiaoxiao Lu, Deming Sun, Xilian Wang, Liyuan Yang, Shaozhen Zhao, Hong Nian, Ruihua Wei
Purpose: To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis. Methods: Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein and hematoxylin and eosin staining. Inflammatory response was determined by measuring the expression of different mediators of inflammation in the lacrimal glands...
October 1, 2016: Investigative Ophthalmology & Visual Science
Hong-Ji Sun, Yan Wang, Tong Hao, Chang-Yong Wang, Qi-Yu Wang, Xiao-Xia Jiang
Glutathione (GSH) depletion has been an important contributor to the dysfunction of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the delivery effect of GSH into PC12 cells was tested. MTT assessment for cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and intracelluar superoxide dismutase (SOD) detection for antioxidative ability were performed. Furthermore, the antiapoptotic ability was analysed by assessing caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells...
October 2016: Regenerative Biomaterials
Qi-Shan Zhang, Yuan-Gao Liao, Zhong Ji, Yong Gu, Hai-Shan Jiang, Zuo-Shan Xie, Su-Yue Pan, Ya-Fang Hu
The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP(+))-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP(+) was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP(+)), scrambled peptide (Scb) (Scb + MPP(+)) and TFP5 (TFP5 + MPP(+)) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups...
October 2016: Experimental and Therapeutic Medicine
Lusi Zhang, Jie Deng, Qian Pan, Yan Zhan, Jian-Bing Fan, Kun Zhang, Zhuohua Zhang
Parkinson disease (PD) is a progressive neurodegenerative movement disorder. Both environmental and genetic factors play important roles in PD etiology. A number of environmental toxins cause parkinsonism in human and animal models. Genetic studies of rare early onset familial PD cases resulted in identification of disease-linked mutations in multiple genes. Nevertheless, the potential interaction between environment and genetics in PD pathogenesis remains largely unknown. We hypothesized that environmental factors induce abnormal epigenetic regulation that is involved in the pathogenesis of both familial and sporadic PD...
May 13, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Xiao-Ming Li, Qi Yang, Xu-Bo Li, Qiang Cheng, Kun Zhang, Jing Han, Jian-Ning Zhao, Gang Liu, Ming-Gao Zhao
Isopsoralen is a type of furocoumarin that exhibits estrogen-like activities. The aim of this study was to determine the estrogen-like neuroprotection of isopsoralen in an animal model of spinal cord injury (SCI). Results indicated that isopsoralen (intraperitoneal injection of 5 and 10 mg/kg per day for two weeks) significantly enhanced the hindlimb locomotor functions of mice with SCI, as revealed in the BMS score and angle of inclined plane tests. Morphological data showed that isopsoralen significantly attenuated the injury of the gray matter of spinal cord and induced the up-regulation of ERα levels...
September 26, 2016: Metabolic Brain Disease
Da-Wei Li, Ying-Di Wang, Shi-Yao Zhou, Wen-Ping Sun
Oxidative stress appears to be a central event responsible for the degeneration of dopaminergic neurons in Parkinson's disease (PD). 1-methyl-4‑phenyl-1,2,3,6-tetrahydropyridine or its toxic metabolite 1‑methyl‑4‑phenylpyridinium (MPP+) are classical widely‑used pharmacological and toxic agents to model PD; they cause the production of reactive oxygen species by inhibiting mitochondrial complex I, leading to DNA oxidative damage and subsequent neuronal death. Previous findings have suggested that proliferating cell nuclear antigen (PCNA), a critical regulatory protein for DNA repair, is involved in dopaminergic neuron damage in the MPP+‑induced PD model...
September 20, 2016: Molecular Medicine Reports
Xavier Descombes
The marked point process framework has been successfully developed in the field of image analysis to detect a configuration of predefined objects. The goal of this paper is to show how it can be particularly applied to biological imagery. We present a simple model that shows how some of the challenges specific to biological data are well addressed by the methodology. We further describe an extension to this first model to address other challenges due, for example, to the shape variability in biological material...
September 21, 2016: Methods: a Companion to Methods in Enzymology
Patrick Oeckl, Boris Ferger
The G-protein coupled receptor 6 (GPR6) is a constitutive active orphan GPCR which is predominantly expressed in striatopallidal neurons. GPR6 deficiency in mice may alter the susceptibility of the nigrostriatal dopaminergic system relevant for Parkinson's disease (PD). Here, we investigated the effect of GPR6 deficiency in mice on neurotoxicity induced by the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). GPR6(-/-)- and control mice were treated with MPTP (4×12.5mg/kg, i.p., 2h intervals) and analyzed after seven days...
September 17, 2016: Neuroscience
Mahesh Ramalingam, Sung-Jin Kim
Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly caused by dopaminergic neuronal cell death. Human neuroblastoma SH-SY5Y cells differentiated by retinoic acid have been used to study the in vitro PD model induced by 1-methyl-4-phenyl pyridinium (MPP(+)). In this study, pretreatment of insulin inhibited MPP(+)-induced cell membrane damages, which also inhibited the Cox-2 and α-synuclein levels. In addition, MPP(+) and/or insulin enhanced the autophagy LC3. Furthermore, MPP(+)-induced neurotoxicity diminished the integrins β3, αV and induced the syndecan-1 and -3...
October 28, 2016: Neuroscience Letters
Andrée-Anne Poirier, Mélissa Côté, Mélanie Bourque, Marc Morissette, Thérèse Di Paolo, Denis Soulet
Motor symptoms in Parkinson's disease (PD) are often preceded by nonmotor symptoms related to dysfunctions of the autonomic nervous system such as constipation, defecatory problems, and delayed gastric emptying. These gastrointestinal impairments are associated with the alteration of dopaminergic (DAergic) neurons in the myenteric plexus of the gut. Recently, we demonstrated the anti-inflammatory properties of estrogens to treat intestinal neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
August 16, 2016: Neurobiology of Aging
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