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https://www.readbyqxmd.com/read/28737745/electromagnetized-gold-nanoparticles-mediate-direct-lineage-reprogramming-into-induced-dopamine-neurons-in-vivo-for-parkinson-s-disease-therapy
#1
Junsang Yoo, Euiyeon Lee, Hee Young Kim, Dong-Ho Youn, Junghyun Jung, Hongwon Kim, Yujung Chang, Wonwoong Lee, Jaein Shin, Soonbong Baek, Wonhee Jang, Won Jun, Soochan Kim, Jongki Hong, Hi-Joon Park, Christopher J Lengner, Sang Hyun Moh, Youngeun Kwon, Jongpil Kim
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes...
July 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28737225/psychostimulant-effect-of-dopaminergic-treatment-and-addictions-in-parkinson-s-disease
#2
Benoit Delpont, Eugénie Lhommée, Hélène Klinger, Emmanuelle Schmitt, Amélie Bichon, Valérie Fraix, Anna Castrioto, Jean-Louis Quesada, Pierre Pélissier, Andrea Kistner, Sébastien Carnicella, Christian Lüscher, Emmanuel Broussolle, Pierre Pollak, Stéphane Thobois, Paul Krack
BACKGROUND: Dopamine replacement therapy in PD has been associated with both behavioral addictions and dopamine addiction. OBJECTIVES: To investigate potential association between l-dopa induced neuropsychiatric fluctuations and addictions in PD. METHODS: A cohort of 102 patients with PD suffering from motor complications of l-dopa treatment was prospectively analyzed. We evaluated dopamine addiction, behavioral addictions, and neuropsychiatric fluctuations using the Ardouin scale of behavior in PD...
July 24, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28736839/the-neurotensin-nts1-receptor-agonist-pd149163-produces-antidepressant-like-effects-in-the-forced-swim-test-further-support-for-neurotensin-as-a-novel-pharmacologic-strategy-for-antidepressant-drugs
#3
Lawrence M Carey, Remington J Rice, Adam J Prus
Preclinical Research Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra-ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS1 receptor agonist, PD149163 produce antidepressant-like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice...
July 24, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28736624/lyme-and-dopaminergic-function-hypothesizing-reduced-reward-deficiency-symptomatology-by-regulating-dopamine-transmission
#4
Kenneth Blum, Edward J Modestino, Marcelo Febo, Bruce Steinberg, Thomas McLaughlin, Lyle Fried, David Baron, David Siwicki, Rajendra D Badgaiyan
The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine...
May 2017: Journal of Systems and Integrative Neuroscience
https://www.readbyqxmd.com/read/28736195/allelic-difference-in-mhc2ta-confers-altered-microglial-activation-and-susceptibility-to-%C3%AE-synuclein-induced-dopaminergic-neurodegeneration
#5
Itzia Jimenez-Ferrer, Michael Jewett, Ashmita Tontanahal, Marina Romero-Ramos, Maria Swanberg
Parkinson Disease (PD) is a complex and heterogeneous neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta and pathological intracellular accumulation of alpha-synuclein (α-syn). In the vast majority of PD patients, the disease has a complex etiology, defined by multiple genetic and environmental risk factors. Common genetic variants in the human leukocyte-antigen (HLA) region have been associated to PD risk and the carriage of these can double the risk to develop PD...
July 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28735099/subcellular-expression-of-aquaporin-4-in-substantia-nigra-of-normal-and-mptp-treated-mice
#6
Agnete Prydz, Katja Stahl, Maja Puchades, Nina Davarpaneh, Maria Nadeem, Ole Petter Ottersen, Vidar Gundersen, Mahmood Amiry-Moghaddam
Aquaporin-4 (AQP4) is the predominant water channel in mammalian CNS where it is localized at the perivascular astrocytic foot processes abutting brain microvessels. Several lines of evidence suggest that AQP4 is involved in important homeostatic functions and that mislocalization of the perivascular pool of AQP4 is implicated in several different brain disorders. A recent study suggests that the differential susceptibility of midbrain dopaminergic neurons to the parkinsonogenic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depends on the expression of AQP4...
July 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28734459/the-roles-of-phasic-and-tonic-dopamine-in-tic%C3%A2-learning-and-expression
#7
REVIEW
Tiago V Maia, Vasco A Conceição
Tourette syndrome (TS) prominently involves dopaminergic disturbances, but the precise nature of those disturbances has remained elusive. A substantial body of empirical work and recent computational models have characterized the specific roles of phasic and tonic dopamine (DA) in action learning and selection, respectively. Using insights from this work and models, we suggest that TS involves increases in both phasic and tonic DA, which produce increased propensities for tic learning and expression, respectively...
June 8, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28734032/characterization-of-the-axon-initial-segment-of-mice-substantia-nigra-dopaminergic-neurons
#8
Cristian González-Cabrera, Rodrigo Meza, Lorena Ulloa, Paulina Merino-Sepúlveda, Valentina Luco, Ana Sanhueza, Alejandro Oñate-Ponce, J Paul Bolam, Pablo Henny
The axon initial segment (AIS) is the site of initiation of action potentials and also influences action potential waveform, firing pattern and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12 - 60 μm) and diameters (0...
July 22, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28733899/6-ohda-induces-oxidation-of-f-box-protein-fbw7%C3%AE-by-chaperone-mediated-autophagy-in-parkinson-s-model
#9
Xiufeng Wang, Heng Zhai, Fang Wang
Parkinson's disease (PD) is the most common movement disorder disease, and its pathological feature is the degenerative loss of dopaminergic neurons in the substantia nigra compacta (SNc). In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanisms. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals' models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity...
July 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28733540/am1241-alleviates-mptp-induced-parkinson-s-disease-and-promotes-the-regeneration-of-da-neurons-in-pd-mice
#10
Jun Shi, Qiong Cai, Jingxing Zhang, Xiaolie He, Yigang Liu, Rongrong Zhu, Lingjing Jin
The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733248/pupil-dilations-induced-by-barely-conscious-reward-goal-priming
#11
Yudai Takarada, Daichi Nozaki
The topic of unconscious influences on behavior has long been explored as a way of understanding human performance and the neurobiological correlates of intention, motivation and action. Previous research using transcranial magnetic stimulation has demonstrated that barely visible priming of an action concept, when combined with reward in the form of a consciously perceived positive stimulus, can alter the state of the motor system and enhance the maximal voluntary force level. One possible explanation is that positive stimulus-induced reward signals are processed by the dopaminergic system in the basal ganglia, motivating individuals to increase the effort they invest in particular behaviors, or to recruit the resources necessary for maintaining those behaviors...
July 18, 2017: Neuropsychologia
https://www.readbyqxmd.com/read/28733161/functional-determination-of-the-differentiation-potential-of-ventral-mesencephalic-neural-precursor-cells-during-dopaminergic-neurogenesis
#12
Gilda Guerrero-Flores, Aimée Bastidas-Ponce, Omar Collazo-Navarrete, Magdalena Guerra-Crespo, Luis Covarrubias
The ventral mesencephalic neural precursor cells (vmNPCs) that give rise to dopaminergic (DA) neurons have been identified by the expression of distinct genes (e.g., Lmx1a, Foxa2, Msx1/2). However, the commitment of these NPCs to the mesencephalic DA neuronal fate has not been functionally determined. Evaluation of the plasticity of vmNPCs suggests that their commitment occurs after E10.5. Here we show that E9.5 vmNPCs implanted in an ectopic area of E10.5 mesencephalic explants, retained their specification marker Lmx1a and efficiently differentiated into neurons but did not express the gene encoding tyrosine hydroxylase (Th), the limiting enzyme for dopamine synthesis...
July 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#13
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730349/manganese-mediated-decrease-in-levels-of-c-ret-and-tyrosine-hydroxylase-expression-in-vitro
#14
Mayuko Y Kumasaka, Ichiro Yajima, Nobutaka Ohgami, Hiromasa Ninomiya, Machiko Iida, Xiang Li, Reina Oshino, Hiroko Tanihata, Masafumi Yoshinaga, Masashi Kato
Previous studies showed that overexposure to manganese causes parkinsonism, a disorder of dopaminergic neurons. Previous studies also showed that activity of c-RET kinase controls dopamine production through regulation of tyrosine hydroxylase (TH) expression, suggesting the involvement of c-RET in the development of parkinsonism. To our knowledge, however, there is no report showing a correlation between manganese-mediated parkinsonism and c-RET. In this study, we examined the effect of manganese on the expression and/or activation levels of c-RET and TH in human TH-expressing cells (TGW cells)...
July 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28729832/the-role-of-microglia-in-retinal-neurodegeneration-alzheimer-s-disease-parkinson-and-glaucoma
#15
REVIEW
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28729827/lateral-hypothalamic-control-of-the-ventral-tegmental-area-reward-evaluation-and-the-driving-of-motivated-behavior
#16
REVIEW
Susan M Tyree, Luis de Lecea
The lateral hypothalamus (LH) plays an important role in many motivated behaviors, sleep-wake states, food intake, drug-seeking, energy balance, etc. It is also home to a heterogeneous population of neurons that express and co-express multiple neuropeptides including hypocretin (Hcrt), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART) and neurotensin (NT). These neurons project widely throughout the brain to areas such as the locus coeruleus, the bed nucleus of the stria terminalis, the amygdala and the ventral tegmental area (VTA)...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28729666/expansion-of-human-midbrain-floor-plate-progenitors-from-induced-pluripotent-stem-cells-increases-dopaminergic-neuron-differentiation-potential
#17
Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729246/vagally-mediated-effects-of-brainstem-dopamine-on-gastric-tone-and-phasic-contractions-of-the-rat
#18
Laura Anselmi, Luca Toti, Cecilia Bove, R Alberto Travagli
Dopamine (DA) containing fibers and neurons are embedded within the brainstem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally-dependent modulation of gastric tone and phasic contractions, i.e. motility, by DA, however, has not been characterized. Using microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were: i) assess the gastric effects of brainstem DA application, ii) identify the DA receptor subtype, and, iii) identify the postganglionic pathway(s) activated...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28728619/restless-genital-syndrome-differential-diagnosis-and-treatment-with-pramipexole
#19
Emilia Sforza, David Hupin, Frédéric Roche
Restless genital syndrome refers to excessive and persistent sensations of genital and clitoral arousal with the absence of conscious feeling of sexual desire. These sensations have been linked to symptoms of restless legs syndrome (RLS) or an overactive bladder. Restless genital syndrome may be related to small fiber sensory neuropathy of the dorsal nerve of the clitoris, so it more frequently occurs in women. The association with RLS suggests a possible dopaminergic mechanism. We report a case of a 74-year-old woman who presented restless genital symptoms every night in association with RLS symptoms...
July 14, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28728428/consequence-of-dopamine-d2-receptor-blockade-on-the-hyperphagic-effect-induced-by-cannabinoid-cb1-and-cb2-receptors-in-layers
#20
M Khodadadi, M Zendehdel, A Baghbanzadeh, V Babapour
1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor induced hyperphagia in 3-h feed-deprived (FD3) neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB1 receptor agonist; 2 µg) and co-adminstration of L-DOPA (125 nmol) plus 2-AG (2 µg)...
July 21, 2017: British Poultry Science
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