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https://www.readbyqxmd.com/read/29332269/behavioral-biochemical-and-molecular-characterization-of-a-parkinson-s-disease-mouse-model-using-the-neurotoxin-2-ch3-mptp-a-novel-approach
#1
Alice Laschuk Herlinger, Agihane Rodrigues Almeida, Sarah Martins Presti-Silva, Evaldo Vitor Pereira, Filipe Andrich, Rita Gomes Wanderley Pires, Cristina Martins-Silva
The neurotoxin MPTP has long been used to create a mouse model of Parkinson's disease (PD). Indeed, several MPTP analogues have been developed, including 2'-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated...
January 13, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29331709/what-do-the-genetic-association-data-say-about-the-high-risk-of-suicide-in-people-with-depression-a-novel-network-based-approach-to-find-common-molecular-basis-for-depression-and-suicidal-behavior-and-related-therapeutic-targets
#2
Ali Bozorgmehr, Fatemeh Alizadeh, Sattar Norouzi Ofogh, Mohammad Reza Abdollahzadeh Hamzekalayi, Sara Herati, Atefeh Moradkhani, Ali Shahbazi, Mohammad Ghadirivasfi
BACKGROUND: Available sources indicate that the risk of suicide in people with major depression is higher than other psychiatric disorders. Although it seems that these two conditions may have a shared cause in some cases, no studies have been conducted to identify a common basis for them. METHODS: In this study, following an extensive review of literature, we found almost all the genes that are involved in major depression and suicidal behavior, and we isolated genes shared between the two conditions...
January 8, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29330488/motor-skill-learning-and-reward-consumption-differentially-affect-vta-activation
#3
Susan Leemburg, Tara Canonica, Andreas Luft
Dopamine release from the ventral tegmental area (VTA) terminals in the primary motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis that dopaminergic VTA neurons projecting to M1 are activated when rewards are obtained during motor skill acquisition, but not during task execution at plateau performance, or by rewards obtained without performing skilled movements. Rats were trained to perform a skilled reaching task for 3 days (acquisition) or 7 days (plateau). In combination with retrograde labelling of VTA-to-M1 projection neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was used to assess activation of dopaminergic and non-dopaminergic VTA neurons...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329581/microrna-124-regulates-the-expression-of-mekk3-in-the-inflammatory-pathogenesis-of-parkinson-s-disease
#4
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29325757/the-role-of-fatty-acids-and-their-endocannabinoid-like-derivatives-in-the-molecular-regulation-of-appetite
#5
REVIEW
Renger F Witkamp
Intake, absorption and synthesis of fatty acids, including those produced by the intestinal microbiota are tightly monitored via specific receptors and, indirectly through their conversion into a variety of signalling molecules. The resulting information is integrated and translated to different physiological processes, including the regulation of appetite and satiation. Direct chemosensing of fatty acids takes place via interaction with free fatty acid (FFA) and other receptors. These are present in the oronasal cavity and along the entire gastrointestinal tract, in various other tissues, and, for some receptors also in brain...
January 8, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29323027/micrornas-in-parkinson-s-disease-and-emerging-therapeutic-targets
#6
REVIEW
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29322941/persistent-activity-in-a-recurrent-circuit-underlies-courtship-memory-in-drosophila
#7
Xiaoliang Zhao, Daniela Lenek, Ugur Dag, Barry Dickson, Krystyna Keleman
Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBg), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ>M6 synapses over time periods that match short-term memory...
January 11, 2018: ELife
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#8
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29314192/parvalbumin-producing-striatal-interneurons-receive-excitatory-inputs-onto-proximal-dendrites-from-the-motor-thalamus-in-male-mice
#9
Yasutake Nakano, Fuyuki Karube, Yasuharu Hirai, Kenta Kobayashi, Hiroyuki Hioki, Shinichiro Okamoto, Hiroshi Kameda, Fumino Fujiyama
In rodents, the dorsolateral striatum regulates voluntary movement by integrating excitatory inputs from the motor-related cerebral cortex and thalamus to produce contingent inhibitory output to other basal ganglia nuclei. Striatal parvalbumin (PV)-producing interneurons receiving this excitatory input then inhibit medium spiny neurons (MSNs) and modify their outputs. To understand basal ganglia function in motor control, it is important to reveal the precise synaptic organization of motor-related cortical and thalamic inputs to striatal PV interneurons...
January 4, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#10
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311646/generation-of-functional-dopaminergic-neurons-from-reprogramming-fibroblasts-by-nonviral-based-mesoporous-silica-nanoparticles
#11
Jen-Hsuan Chang, Ping-Hsing Tsai, Kai-Yi Wang, Yu-Ting Wei, Shih-Hwa Chiou, Chung-Yuan Mou
Direct-lineage conversion of the somatic cell by reprogramming, in which mature cells were fully converted into a variety of other cell types bypassing an intermediate pluripotent state, is a promising regenerative medicine approach. Due to the risk of tumorigenesis by viral methods, a non-viral carrier for the delivery of reprogramming factors is very desirable. This study utilized the mesoporous silica nanoparticles (MSNs) as a non-viral delivery system for transduction of the three key factors to achieve conversion of mouse fibroblasts (MFs) into functional dopaminergic neuron-like cells (denoted as fDA-neurons)...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311330/gba1-deficiency-negatively-affects-physiological-%C3%AE-synuclein-tetramers-and-related-multimers
#12
Sangjune Kim, Seung Pil Yun, Saebom Lee, George Essien Umanah, Veera Venkata Ratnam Bandaru, Xiling Yin, Peter Rhee, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Hojae Lee, Xiaobo Mao, Donghoon Kim, Akhilesh Pandey, Gabsang Lee, Valina L Dawson, Ted M Dawson, Han Seok Ko
Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311261/towards-stem-cell-based-therapies-for-parkinson-s-disease
#13
Malin Parmar
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming...
January 8, 2018: Development
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#14
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29308644/near-infrared-fluorescent-nanoprobes-for-revealing-the-role-of-dopamine-in-drug-addiction
#15
Peijian Feng, Yulei Chen, Lei Zhang, Cheng-Gen Qian, Xuanzhong Xiao, Xu Han, Qun-Dong Shen
Brain imaging techniques enable visualizing the activity of central nervous system without invasive neurosurgery. Dopamine is an important neurotransmitter. Its fluctuation in brain leads to a wide range of diseases and disorders, like drug addiction, depression, and Parkinson disease. We designed near-infrared fluorescence dopamine-responsive nanoprobes (DRNs) for brain activity imaging during drug abuse and addiction process. Based on light-induced electron transfer between DRNs and dopamine and molecular wire effect of the DRNs, we can track dynamical change of the neurotransmitter level in the physiological environment and the releasing of the neurotransmitter in living dopaminergic neurons in response to nicotine stimulation...
January 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29307179/comparison-of-adaptive-neuroprotective-mechanisms-of-sulforaphane-and-its-interconversion-product-erucin-in-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#16
Fabiana Morroni, Giulia Sita, Alice Djemil, Massimo D'Amico, Letizia Pruccoli, Giorgio Forti, Patrizia Hrelia, Andrea Tarozzi
Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN...
January 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29305892/the-involvement-of-the-pathway-connecting-the-substantia-nigra-the-periaqueductal-gray-matter-and-the-retrotrapezoid-nucleus-in-breathing-control-in-a-rat-model-of-parkinson-s-disease
#17
Juliana C Lima, Luiz M Oliveira, Marina T Botelho, Thiago S Moreira, Ana C Takakura
Parkinson's disease (PD) is characterized by a reduction in the number of dopaminergic neurons of the substantia nigra (SNpc), accompanied by motor and non-motor deficiencies such as respiratory failure. Here, our aim was to investigate possible neuronal communications between the SNpc and chemoreceptor neurons within the retrotrapezoid nucleus (RTN), in order to explain neurodegeneration and the loss of breathing function in the 6-OHDA PD animal model. Male Wistar rats received tracer injections in the SNpc, RTN and periaqueductal gray (PAG) regions to investigate the projections between those regions...
January 4, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29305570/neurotrophic-factors-hold-promise-for-the-future-of-parkinson-s-disease-treatment-is-there-a-light-at-the-end-of-the-tunnel
#18
Ava Nasrolahi, Javad Mahmoudi, Abolfazl Akbarzadeh, Mohammad Karimipour, Saeed Sadigh-Eteghad, Roya Salehi, Mehdi Farhoudi
Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a spectrum of clinicopathologic signs and a complex etiology. PD results from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra. Current therapies for PD are only able to alleviate symptoms without stopping disease progression. In addition, the available therapeutic strategies do not have long-lasting effects. Furthermore, these therapies cause different ranges of adverse side effects...
January 6, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29304113/discovery-of-indolylpiperazinylpyrimidines-with-dual-target-profiles-at-adenosine-a2a-and-dopamine-d2-receptors-for-parkinson-s-disease-treatment
#19
Yi-Ming Shao, Xiaohua Ma, Priyankar Paira, Aaron Tan, Deron Raymond Herr, Kah Leong Lim, Chee Hoe Ng, Gopalakrishnan Venkatesan, Karl-Norbert Klotz, Stephanie Federico, Giampiero Spalluto, Siew Lee Cheong, Yu Zong Chen, Giorgia Pastorin
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects...
2018: PloS One
https://www.readbyqxmd.com/read/29302200/reexamination-of-dopaminergic-amacrine-cells-in-the-rabbit-retina-confocal-analysis-with-double-and-triple-labeling-immunohistochemistry
#20
Jong Woo Lee, Min Young Lim, Yong Soo Park, Su Jin Park, In-Beom Kim
Dopaminergic amacrine cells (DACs) are among the most well-characterized neurons in the mammalian retina, and their connections to AII amacrine cells have been described in detail. However, the stratification of DAC dendrites differs based on their location in the inner plexiform layer (IPL), raising the question of whether all AII lobules are modulated by dopamine release from DACs. The present study aimed to clarify the relationship between DACs and AII amacrine cells, and to further elucidate the role of dopamine at synapses with AII amacrine cell...
December 2017: Experimental Neurobiology
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