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https://www.readbyqxmd.com/read/28342134/dopaminergic-neuron-specific-deletion-of-p53-gene-attenuates-methamphetamine-neurotoxicity
#1
Tao Lu, Paul P Kim, Nigel H Greig, Yu Luo
p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO...
March 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28341600/metabolic-disorder-dysfunction-in-parkinson-s-disease-bioenergetics-redox-homeostasis-and-central-carbon-metabolism
#2
Annadurai Anandhan, Maria S Jacome, Shulei Lei, Pablo Hernandez-Franco, Aglaia Pappa, Mihalis I Panayiotidis, Robert Powers, Rodrigo Franco
The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic process in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival...
March 21, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28341570/a-study-of-the-age-related-effects-of-lactational-atrazine-exposure
#3
Yan Sun, Yan-Shu Li, Bai Li, Kun Ma, Bai-Xiang Li
A growing number of reports have demonstrated that the widely-used herbicide Atrazine (ATR) can cause injury to dopamine (DA) neurons, but the exact mechanism remains unclear. In this study, we examined the effects of lactational ATR exposure in Sprague-Dawley rats on dopaminergic neuron health later in life. Compared with control rats, rats exposed to ATR during a critical period of neural development showed decreased striatal DA content and increased rates of DA turnover. The expression of Monoamine oxidase (MAO), which is associated with DA degradation, was up-regulated, and the expression of Vesicular Monoamine Transporter 2 (VMAT2), which is associated with DA transport, was down-regulated...
March 21, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28339776/effect-of-acute-millimeter-wave-exposure-on-dopamine-metabolism-of-ngf-treated-pc12-cells
#4
Alexis J Haas, Yann Le Page, Maxim Zhadobov, Ronan Sauleau, Yves Le Dréan, Christian Saligaut
Several forthcoming wireless telecommunication systems will use electromagnetic frequencies at millimeter waves (MMWs), and technologies developed around the 60-GHz band will soon know a widespread distribution. Free nerve endings within the skin have been suggested to be the targets of MMW therapy which has been used in the former Soviet Union. So far, no studies have assessed the impact of MMW exposure on neuronal metabolism. Here, we investigated the effects of a 24-h MMW exposure at 60.4 GHz, with an incident power density (IPD) of 5 mW/cm², on the dopaminergic turnover of NGF-treated PC12 cells...
February 24, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28337696/cerebral-dopamine-neurotrophic-factor-a-potential-therapeutic-agent-for-parkinson-s-disease
#5
REVIEW
Tingting Tang, Yong Li, Qian Jiao, Xixun Du, Hong Jiang
The application of neurotrophic factors (NTFs) is a promising therapeutic strategy for neurodegenerative disorders such as Parkinson's disease (PD). Many NTFs have been reported to enhance the survival, regeneration, and differentiation of neurons and to induce synaptic plasticity. However, because of their potential side-effects and low efficacy after clinical administration, more potent treatments for neurodegenerative disorders are being sought. Cerebral dopamine neurotrophic factor (CDNF), a newly-identified NTF homologous to mesencephalic astrocyte-derived NTF, is structurally and functionally different from other NTFs, providing new hope especially for PD patients...
March 23, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28337287/memri-is-a-biomarker-defining-nicotine-specific-neuronal-responses-in-subregions-of-the-rodent-brain
#6
Aditya N Bade, Howard E Gendelman, Michael D Boska, Yutong Liu
Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#7
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28336568/cholinergic-but-not-dopaminergic-or-noradrenergic-enhancement-sharpens-visual-spatial-perception-in-humans
#8
Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L Wallace, Mark D'Esposito, Michael A Silver
The neuromodulator acetylcholine (ACh) modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects...
March 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28335015/the-synaptic-function-of-parkin
#9
Jenny Sassone, GiuliaMaia Serratto, Flavia Valtorta, Vincenzo Silani, Maria Passafaro, Andrea Ciammola
Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334019/cell-survival-and-differentiation-with-nanocrystalline-glass-like-carbon-using-substantia-nigra-dopaminergic-cells-derived-from-transgenic-mouse-embryos
#10
Noela Rodriguez-Losada, Pablo Romero, Guillermo Estivill-Torrús, Roberto Guzmán de Villoria, Jose A Aguirre
Regenerative medicine requires, in many cases, physical supports to facilitate appropriate cellular architecture, cell polarization and the improvement of the correct differentiation processes of embryonic stem cells, induced pluripotent cells or adult cells. Because the interest in carbon nanomaterials has grown within the last decade in light of a wide variety of applications, the aim of this study was to test and evaluate the suitability and cytocompatibility of a particular nanometer-thin nanocrystalline glass-like carbon film (NGLC) composed of curved graphene flakes joined by an amorphous carbon matrix...
2017: PloS One
https://www.readbyqxmd.com/read/28332824/indole-substituted-benzothiazoles-and-benzoxazoles-as-selective-and-reversible-mao-b-inhibitors-for-treatment-of-parkinson-s-disease
#11
Min-Ho Nam, Moosung Park, Hyeri Park, Youngjae Kim, Seulki Yoon, Vikram Shahaji Sawant, Ji Won Choi, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Changjoon Justin Lee, Hyunah Choo
To develop a novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was Compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 29 nM with no apparent effect on MAO-A activity at 10 M. Based on the reversibility assay, Compound 5b turned out to be a fully reversible with over 95% of recovery of enzyme activity after washout of the compound...
March 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28332590/nicotine-enhances-alcohol-intake-and-dopaminergic-responses-through-%C3%AE-2-and-%C3%AE-4-nicotinic-acetylcholine-receptors
#12
Stefania Tolu, Fabio Marti, Carole Morel, Carole Perrier, Nicolas Torquet, Stephanie Pons, Renaud de Beaurepaire, Philippe Faure
Alcohol and nicotine are the most widely co-abused drugs. Both modify the activity of dopaminergic (DA) neurons of the Ventral Tegmental Area (VTA) and lead to an increase in DA release in the Nucleus Accumbens, thereby affecting the reward system. Evidences support the hypothesis that distinct nicotinic acetylcholine receptors (nAChRs), the molecular target of acetylcholine (ACh) and exogenous nicotine, are also in addition implicated in the response to alcohol. The precise molecular and neuronal substrates of this interaction are however not well understood...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#13
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28331322/the-role-of-deep-brain-stimulation-in-parkinson-s-disease-an-overview-and-update-on-new-developments
#14
REVIEW
John Y Fang, Christopher Tolleson
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of neuronal dopamine production in the brain. Oral therapies primarily augment the dopaminergic pathway. As the disease progresses, more continuous delivery of therapy is commonly needed. Deep brain stimulation (DBS) has become an effective therapy option for several different neurologic and psychiatric conditions, including PD. It currently has US Food and Drug Administration approval for PD and essential tremor, as well as a humanitarian device exception for dystonia and obsessive-compulsive disorder...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28331029/the-sac1-domain-in-synaptojanin-is-required-for%C3%A2-autophagosome-maturation-at-presynaptic%C3%A2-terminals
#15
Roeland Vanhauwaert, Sabine Kuenen, Roy Masius, Adekunle Bademosi, Julia Manetsberger, Nils Schoovaerts, Laura Bounti, Serguei Gontcharenko, Jef Swerts, Sven Vilain, Marina Picillo, Paolo Barone, Shashini T Munshi, Femke Ms de Vrij, Steven A Kushner, Natalia V Gounko, Wim Mandemakers, Vincenzo Bonifati, Frederic A Meunier, Sandra-Fausia Soukup, Patrik Verstreken
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in Synaptojanin(RQ) knock-in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes...
March 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28329817/early-life-benzo-a-pyrene-exposure-causes-neurodegenerative-syndromes-in-adult-zebrafish-danio-rerio-and-the-mechanism-involved
#16
Dongxu Gao, Chonggang Wang, Zhihui Xi, Yixi Zhou, Yuanchuan Wang, Zhenghong Zuo
There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration...
January 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28327638/conditional-deletion-of-ndufs4-in-dopaminergic-neurons-promotes-parkinson-s-disease-like-non-motor-symptoms-without-loss-of-dopamine-neurons
#17
Won-Seok Choi, Hyung-Wook Kim, François Tronche, Richard D Palmiter, Daniel R Storm, Zhengui Xia
Reduction of mitochondrial complex I activity is one of the major hypotheses for dopaminergic neuron death in Parkinson's disease. However, reduction of complex I activity in all cells or selectively in dopaminergic neurons via conditional deletion of the Ndufs4 gene, a subunit of the mitochondrial complex I, does not cause dopaminergic neuron death or motor impairment. Here, we investigated the effect of reduced complex I activity on non-motor symptoms associated with Parkinson's disease using conditional knockout (cKO) mice in which Ndufs4 was selectively deleted in dopaminergic neurons (Ndufs4 cKO)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324006/effects-of-season-and-estradiol-on-kndy-neuron-peptides-colocalization-with-d2-dopamine-receptors-and-dopaminergic-inputs-in-the-ewe
#18
Peyton Weems, Jeremy Smith, Iain J Clarke, Lique M Coolen, Robert L Goodman, Michael N Lehman
Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the non-breeding season (anestrus). Recent findings suggest that KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322751/neuroprotective-effects-of-2-4-dinitrophenol-in-an-acute-model-of-parkinson-s-disease
#19
Yujeong Lee, Gwangbeom Heo, Kyung Moon Lee, Ah Hyun Kim, Ki Wung Chung, Eunok Im, Hae Young Chung, Jaewon Lee
Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson's disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5 mg/kg) for 12 consecutive days, and then on day 13, MPTP (20 mg/kg, i...
March 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28322275/oxidative-stress-driven-parvalbumin-interneuron-impairment-as-a-common-mechanism-in-models-of-schizophrenia
#20
P Steullet, J-H Cabungcal, J Coyle, M Didriksen, K Gill, A A Grace, T K Hensch, A-S LaMantia, L Lindemann, T M Maynard, U Meyer, H Morishita, P O'Donnell, M Puhl, M Cuenod, K Q Do
Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition...
March 21, 2017: Molecular Psychiatry
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