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https://www.readbyqxmd.com/read/29150590/subtype-specific-effects-of-dopaminergic-d2-receptor-activation-on-synaptic-trains-in-layer-v-pyramidal-neurons-in-the-mouse-prefrontal-cortex
#1
Jonna M Leyrer-Jackson, Mark P Thomas
In humans, prefrontal cortical areas are known to support executive functions. In mice, these functions are mediated by homologous regions in the medial prefrontal cortex (mPFC). Executive processes are critically dependent on optimal levels of dopamine (DA), but the cellular mechanisms of DA modulation are incompletely understood. Stable patterns of neuronal activity may be sensitive to frequency-dependent changes in synaptic transmission. We characterized the effects of D2 receptor (D2R) activation on short-term excitatory postsynaptic potential (EPSP) dynamics evoked at varying frequencies in the two subtypes of layer V pyramidal neurons in mouse mPFC We isolated NMDA receptor and non-NMDA receptor-mediated components of EPSP trains evoked by stimulating fibers within layer V or layer I...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29150520/dopaminergic-neurotoxins-induce-cell-death-by-attenuating-nf-%C3%AE%C2%BAb-mediated-regulation-of-trpc1-expression-and-autophagy
#2
Pramod Sukumaran, Yuyang Sun, Neil Antonson, Brij B Singh
Alterations in Ca(2+) homeostasis affect neuronal survival. However, the identity of Ca(2+) channels and the mechanisms underlying neurotoxin-induced neuronal degeneration are not well understood. In this study, the dopaminergic neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl -4-phenylpyridium ions (MPP(+)/MPTP), which mimic Parkinson's disease (PD), induced neuronal degeneration by decreasing store-mediated Ca(2+) entry. The function of the transient receptor potential canonical (TRPC)-1 channel was decreased upon exposure to the neurotoxins, followed by a decrease in TRPC1 expression...
November 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29149825/dopamine-agonists-and-neurodegenerative-disorders
#3
Saba Khanam, Yasir Hasan Siddique
Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons within the substantia nigra pars compacta. Despite of many researches, there is still no cure for this disease. Levodopa is first line treatment of PD, but the long term use of it leads to motor impairments and dyskinesias. The dopamine agonists are the preferred choice for the treatment of PD. They are neuroprotective in nature but also have side effects. In this review, we highlighted the metabolism of dopamine, different types of dopamine agonists with their properties and possible side effects...
November 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29149768/mitochondrial-dna-changes-in-pedunculopontine-cholinergic-neurons-in-parkinson-s
#4
Alexander G Bury, Angela Pyle, Joanna L Elson, Laura Greaves, Christopher M Morris, Gavin Hudson, Ilse S Pienaar
In Parkinson's disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co-occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from post-mortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation...
November 17, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#5
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29147910/therapeutic-activities-of-dj-1-and-its-binding-compounds-against-neurodegenerative-diseases
#6
Masatoshi Inden, Daijiro Yanagisawa, Masanori Hijioka, Hiroyoshi Ariga, Yoshihisa Kitamura
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Previously, we identified binding compounds of DJ-1, including UCP0045037/compound A, UCP0054278/compound B, and compound-23 (comp-23), by in silico virtual screening. These compounds prevented oxidative stress-induced dopaminergic neuronal death and restored locomotion defects in animal models of PD...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29145874/peripheral-immune-tolerance-alleviates-the-intracranial-lipopolysaccharide-injection-induced-neuroinflammation-and-protects-the-dopaminergic-neurons-from-neuroinflammation-related-neurotoxicity
#7
Yang Liu, Xin Xie, Li-Ping Xia, Hong Lv, Fan Lou, Yan Ren, Zhi-Yi He, Xiao-Guang Luo
BACKGROUND: Neuroinflammation plays a critical role in the onset and development of neurodegeneration disorders such as Parkinson's disease. The immune activities of the central nervous system are profoundly affected by peripheral immune activities. Immune tolerance refers to the unresponsiveness of the immune system to continuous or repeated stimulation to avoid excessive inflammation and unnecessary by-stander injury in the face of continuous antigen threat. It has been proved that the immune tolerance could suppress the development of various peripheral inflammation-related diseases...
November 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29142291/resveratrol-modulates-cocaine-induced-inhibitory-synaptic-plasticity-in-vta-dopamine-neurons-by-inhibiting-phosphodiesterases-pdes
#8
Yan Li, Laikang Yu, Li Zhao, Fanxing Zeng, Qing-Song Liu
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142100/abnormal-visual-gain-control-and-excitotoxicity-in-early-onset-parkinson-s-disease-drosophila-models
#9
Marc Mason Himmelberg, Ryan J H West, Christopher J H Elliott, Alex R Wade
The excitotoxic theory of Parkinson's disease (PD) hypothesises that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD Drosophila models DJ-1Δ72, DJ1-Δ93, and PINK15. We used an electroretinogram to record steady state visually evoked potentials driven by temporal contrast stimuli...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29139159/syntaxin1b-contributes-to-regulation-of-the-dopaminergic-system-through-gaba-transmission-in-the-cns
#10
Tomonori Fujiwara, Takefumi Kofuji, Tatsuya Mishima, Kimio Akagawa
In neuronal plasma membrane, two syntaxin isoforms, HPC-1/syntaxin1A (STX1A) and syntaxin1B (STX1B), are predominantly expressed as soluble N-ethylmaleimide-sensitive fusion attachment protein receptors, also known as t-SNAREs. We previously reported that glutamatergic and GABAergic synaptic transmission is impaired in Stx1b null mutant (Stx1b(-/-) ) mice, but is almost normal in Stx1a null mutant (Stx1a(-/-) ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS)...
November 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29138490/bidirectional-modulation-of-hippocampal-synaptic-plasticity-by-dopaminergic-d4-receptors-in-the-ca1-area-of-hippocampus
#11
Sheeja Navakkode, Katherine C M Chew, Sabrina Jia Ning Tay, Qingshu Lin, Thomas Behnisch, Tuck Wah Soong
Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138117/melatonin-protects-against-behavioral-deficits-dopamine-loss-and-oxidative-stress-in-homocysteine-model-of-parkinson-s-disease
#12
Rajib Paul, Banashree Chetia Phukan, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Pallab Bhattacharya, Anupom Borah
AIM: Hyperhomocysteinemia and homocysteine (Hcy) mediated dopaminergic neurotoxicity is a matter of concern in the pathophysiology of Parkinson's disease (PD). Our previous study established the involvement of oxidative stress in the substantia nigra (SN) of Hcy rat model of PD; however, the role of antioxidants, such as melatonin, was not tested in this model. MAIN METHODS: Melatonin (10, 20 and 30mg/kg, i.p.) was administered to rats injected with Hcy in right SN (1...
November 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/29138105/adrenergic-receptor-agonists-modulation-of-dopaminergic-and-non-dopaminergic-neurons-in-the-ventral-tegmental-area
#13
Kamil Pradel, Tomasz Blasiak, Wojciech B Solecki
The ventral tegmental area (VTA) neuronal population consists of dopaminergic (DAergic) and non-DAergic neurons (mainly GABAergic), the activity of which is intertwined with VTA behavioural functions. Both DAergic and GABAergic neurons in the VTA have been shown to express adrenergic receptors (ARs) and respond to AR stimulation. The aim of the present study was to demonstrate the effects of selective AR agonists on DAergic and non-DAergic neuronal activity in the central and lateral parts of the VTA using in vivo electrophysiological recording combined with microiontophoretic drug application in anaesthetized rats...
November 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/29137186/dopaminergic-dysfunction-in-mammalian-dopamine-neurons-induced-by-simazine-neurotoxicity
#14
Xueting Li, Jia Yu, Jianan Li, Yanping Wu, Baixiang Li
Many studies have shown that the pollutant simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine), which has been overused, inhibits the proliferation of mammalian dopaminergic cells, and affects the developmental differentiation of mammalian dopaminergic neurons. However, few studies have shown the effects of simazine on dopaminergic metabolism in these cells. Therefore, we aim to examine the metabolic effects of simazine exposure in mouse dopaminergic progenitor neurons (MN9D) at different exposure times...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29137045/the-significance-of-uric-acid-in-the-diagnosis-and-treatment-of-parkinson-disease-an-updated-systemic-review
#15
Zhange Yu, Shuai Zhang, Dongdong Wang, Meng Fan, Fuqiang Gao, Wei Sun, Zirong Li, Shiliang Li
BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative stress is proposed to play a critical role in the pathogenesis of PD. Uric acid (UA), as an important physiological antioxidant, is identified a molecular predictor associated with a decreased risk and a slower disease progression for PD and potential neuroprotectant of PD by increasing epidemiological and clinical evidences...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29134560/neurochemical-and-neurotoxic-effects-of-mdma-ecstasy-and-caffeine-after-chronic-combined-administration-in-mice
#16
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29133394/role-of-estrogen-receptor-beta-in-neural-differentiation-of-mouse-embryonic-stem-cells
#17
Mukesh K Varshney, José Inzunza, Diana Lupu, Vaidheeswaran Ganapathy, Per Antonson, Joëlle Rüegg, Ivan Nalvarte, Jan-Åke Gustafsson
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132545/nanoformulation-a-useful-therapeutic-strategy-for-improving-neuroprotection-and-the-neurorestorative-potential-in-experimental-models-of-parkinson-s-disease
#18
Jose V Lafuente, Catalina Requejo, Alejandro Carrasco, Harkaitz Bengoetxea
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle (MFB) or into the striatum in rats affords to study various stages of PD depending on the evolution time lapsed. A promising alternative to address the neurodegenerative process is the use of neurotrophic factors; but its clinical use has been limited due to its short half-life and rapid degradation after in vivo administration, along with difficulties for crossing the blood-brain barrier (BBB)...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#19
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29130486/rtp801-is-a-critical-factor-in-the-neurodegeneration-process-of-a53t-alpha-synuclein-in-a-mouse-model-of-parkinson-s-disease-under-chronic-restraint-stress
#20
Zhao Zhang, Shi-Feng Chu, Sha-Sha Wang, Yi-Na Jiang, Yan Gao, Peng-Fei Yang, Qi-Di Ai, Nai-Hong Chen
BACKGROUND AND PURPOSE: The incidence of Parkinson's disease exhibited a younger tendency in recent years with the constantly increased stressors of modern society, but this relationship remains obscured. We performed this study to investigate whether stress contributes to this tendency and identify the executor during this process. EXPERIMENTAL APPROACH: Ten-month-old α-synuclein A53T mice, a PD mice model, were treated with chronic restraint stress (CRS) to simulate a PD-sensitive person with constant stress stimulation...
November 11, 2017: British Journal of Pharmacology
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