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https://www.readbyqxmd.com/read/29779176/intranasal-delivery-of-pgdnf-dna-nanoparticles-provides-neuroprotection-in-the-rat-6-hydroxydopamine-model-of-parkinson-s-disease
#1
Amirah E-E Aly, Brendan T Harmon, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J Cooper, Barbara L Waszczak
Glial cell line-derived neurotrophic factor (GDNF) gene therapy could offer a disease-modifying treatment for Parkinson's disease (PD). Here, we report that plasmid DNA nanoparticles (NPs) encoding human GDNF administered intranasally to rats induce transgene expression in the brain and protect dopamine neurons in a model of PD. To first test whether intranasal administration could transfect cells in the brain, rats were sacrificed 1 week after intranasal pGDNF NPs or the naked plasmid. GDNF ELISA revealed significant increases in GDNF expression throughout the brain for both treatments...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29779103/dopamine-synthesis-as-a-mechanism-of-brain-plasticity-in-nigrostriatal-system-pathology
#2
A A Kolacheva, M V Ugrumov
Using an experimental Parkinson's disease model (symptoms develop in mice after the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), we studied the characteristics of the synthesis of dopamine as a possible compensatory mechanism aimed at maintaining the dopamine level in the dopaminergic neurons that survived in this pathology. We found no correlation between the content and activity of tyrosine hydroxylase in the nigrostriatal system. The enzyme activity and the dopamine content showed unidirectional changes in the substantia nigra, but not in the striatum, which is apparently due to triggering other compensatory mechanisms...
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29778010/exposure-to-cannabinoid-agonist-win-55-212-2-during-early-adolescence-increases-alcohol-preference-and-anxiety-in-cd1-mice
#3
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29777006/in-vivo-characterization-and-quantification-of-neurofibrillary-tau-pet-radioligand-18-f-mk-6240-in-humans-from-alzheimer-s-disease-dementia-to-young-controls
#4
Tobey J Betthauser, Karly A Cody, Matthew D Zammit, Dhanabalan Murali, Alexander K Converse, Todd E Barnhart, Charles K Stone, Howard A Rowley, Sterling C Johnson, Bradley T Christian
Tau positron emission tomography (PET) imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer's disease (AD). This work investigates in vivo kinetics, quantification strategies and imaging characteristics of a novel tau PET radioligand [18 F]MK-6240 in humans. Methods: Fifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted magnetic resonance imaging (MRI), and [11 C]PiB and [18 F]MK-6240 PET imaging...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29773980/anatomical-inputs-from-the-sensory-and-value-structures-to-the-tail-of-the-rat-striatum
#5
Haiyan Jiang, Hyoung F Kim
The caudal region of the rodent striatum, called the tail of the striatum (TS), is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS) in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29773830/circadian-and-homeostatic-modulation-of-multi-unit-activity-in-midbrain-dopaminergic-structures
#6
Karim Fifel, Johanna H Meijer, Tom Deboer
Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#7
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29772432/silymarin-prevents-apoptosis-through-inhibiting-the-bax-caspase-3-expression-and-suppresses-toll-like-receptor-4-pathway-in-the-snc-of-6-ohda-intoxicated-rats
#8
Rasool Haddadi, Alireza Mohajjel Nayebi, Shahla Eyvari Brooshghalan
BACKGROUND AND PURPOSE: Several lines of evidence show that apoptosis, oxidative stress and neuroinflammation are associated with the development of Parkinson's disease (PD). In the present study, we investigated the effect of pre-treatment with silymarin (SM) on oxidative stress, apoptosis and toll-like receptor 4 (TLR4) expression in substantia nigra pars copmacta (SNc) of 6-hydroxydopamine (6-OHDA)-lesioned rats. METHODS: Animals were pretreated with 100, 200 or 300 mg/kg of SM daily for 5 days and at 6th day 6-OHDA (8 μg/2 μl) was infused unilaterally into the central region of the SNc...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29769744/nadph-ameliorates-mptp-induced-dopaminergic-neurodegeneration-through-inhibiting-p38mapk-activation
#9
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+ ...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29766664/tissue-engineered-nigrostriatal-pathway-for-treatment-of-parkinson-s-disease
#10
Laura A Struzyna, Kevin D Browne, Zachary D Brodnik, Justin C Burrell, James P Harris, H Isaac Chen, John A Wolf, Kate V Panzer, James Lim, John E Duda, Rodrigo A España, D Kacy Cullen
The classic motor deficits of Parkinson's disease are caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of their long-distance axonal projections that modulate the striatum. Current treatments only minimize the symptoms of this disconnection as there is no approach capable of replacing the nigrostriatal pathway. We are applying micro-tissue engineering techniques to create living, implantable constructs that mimic the architecture and function of the nigrostriatal pathway...
May 15, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29766510/ineffectiveness-of-saxagliptin-as-a-neuroprotective-drug-in-6-ohda-lesioned-rats
#11
Joelle de Melo Turnes, Taysa Bervian Bassani, Leonardo C Souza, Maria A B F Vital
OBJECTIVES: To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. METHODS: Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days...
May 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29761857/downregulated-expression-of-microrna-329-inhibits-apoptosis-of-nigral-dopaminergic-neurons-by-regulating-cdkn2d-expression-via-the-foxo3a-signaling-pathway-in-rats-with-parkinson-s-disease
#12
Yuan-Yuan Liu, Yi-Nan Zhang, Qing-Shan Yang
Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA-329 (miR-329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)-positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR-329 mimics, miR-329 inhibitors, small interfering (siRNA)-CDKN2D, and miR-329 inhibitors + siRNA-CDKN2D groups...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29761003/the-asymmetry-of-neural-symptoms-in-wilson-s-disease-patients-detecting-by-diffusion-tensor-imaging-resting-state-functional-mri-and-susceptibility-weighted-imaging
#13
Xiang-Xue Zhou, Xun-Hua Li, Ding-Bang Chen, Chao Wu, Li Feng, Jian-Ping Chu, Zhi-Yun Yang, Xin-Bei Li, Haolin Qin, Gui-Dian Li, Hai-Wei Huang, Ying-Ying Liang, Xiu-Ling Liang
Objective: To investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI. Methods: Fifty patients with WD and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and resting-state functional MRI (rs-fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs-fMRI were determined...
May 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29760428/generation-and-characterisation-of-a-parkin-pacrg-knockout-mouse-line-and-a-pacrg-knockout-mouse-line
#14
Sarah E M Stephenson, Timothy D Aumann, Juliet M Taylor, Jessica R Riseley, Ruili Li, Jeffrey R Mann, Doris Tomas, Paul J Lockhart
Mutations in PARK2 (parkin) can result in Parkinson's disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760287/-multi-organ-distribution-of-alpha-synuclein-pathology-in-dementia-with-lewy-bodies
#15
Koichi Wakabayashi, Yasuo Miki
In Parkinson's disease and dementia with Lewy bodies, neuronal α-synuclein aggregates (Lewy bodies and Lewy neurites) are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla, and skin. Lewy bodies also occur in 10-20% of neurologically asymptomatic individuals older than 60 years. These cases are called incidental Lewy body disease (ILBD). In ILBD, Lewy bodies can be found in the brain, spinal cord, sympathetic ganglia, visceral autonomic nervous system and skin...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29758227/effects-of-feedback-delay-on-learning-from-positive-and-negative-feedback-in-patients-with-parkinson-s-disease-off-medication
#16
Benjamin Weismüller, Marta Ghio, Kazimierz Logmin, Christian Hartmann, Alfons Schnitzler, Bettina Pollok, Martin Südmeyer, Christian Bellebaum
Phasic dopamine (DA) signals conveyed from the substantia nigra to the striatum and the prefrontal cortex crucially affect learning from feedback, with DA bursts facilitating learning from positive feedback and DA dips facilitating learning from negative feedback. Consequently, diminished nigro-striatal dopamine levels as in unmedicated patients suffering from Parkinson's Disease (PD) have been shown to lead to a negative learning bias. Recent studies suggested a diminished striatal contribution to feedback processing when the outcome of an action is temporally delayed...
May 11, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29756399/distinct-progression-pattern-of-susceptibility-mri-in-the-substantia-nigra-of-parkinson-s-patients
#17
Guangwei Du, Mechelle M Lewis, Christopher Sica, Lu He, James R Connor, Lan Kong, Richard B Mailman, Xuemei Huang
BACKGROUND: Susceptibility MRI may capture Parkinson's disease-related pathology. This study delineated longitudinal changes in different substantia nigra regions. METHODS: Seventy-two PD patients and 62 controls were studied at both baseline and after 18 months with MRI. R2* and quantitative susceptibility mapping values from the substantia nigra pars compacta and substantia nigra pars reticulata were calculated. Mixed-effects models compared controls with PD or PD subgroups having different disease durations: early (<1 year), middle (<5 years, middle-stage PD), and late (>5 years, late-stage PD)...
May 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29756356/neuroimaging-abnormalities-in-individuals-exhibiting-parkinson-s-disease-risk-markers
#18
Marcus Heldmann, Janna Heeren, Christine Klein, Linus Rauch, Johann Hagenah, Thomas F Münte, Meike Kasten, Norbert Brüggemann
BACKGROUND: The concept of prodromal Parkinson's disease (PD) involves variable combinations of nonmotor features and subtle motor abnormalities as a result of ongoing neurodegeneration in the brain stem including substantia nigra (SN) and abnormal findings upon transcranial sonography and nuclear imaging. Except for nuclear imaging, the predictive value of risk markers for the conversion to overt PD is low. OBJECTIVE: The objective of this study was to determine whether PD risk markers are associated with changes in brain structure and to what extent cognitive changes are risk markers for PD...
May 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29755536/preclinical-study-of-ibuprofen-loaded-transnasal-mucoadhesive-microemulsion-for-neuroprotective-effect-in-mptp-mice-model
#19
Surjyanarayan Mandal, Snigdha Das Mandal, Krishna Chuttani, Krutika K Sawant, Bharat Bhushan Subudhi
Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), showed very promising neuroprotection action, but it suffers from high first pass metabolism and limited ability to cross blood brain barrier. Severe gastric toxicity following oral administration further limits its utility. Hence, the aim of this study was to investigate whether ibuprofen loaded mucoadhesive microemulsion (MMEI) could enhance the brain uptake and could also protect the dopaminergic neurons from MPTP-mediated neural inflammation. In this work, ibuprofen loaded polycarbophil based mucoadhesive microemulsion (MMEI) was developed by using response surface methodology (RSM)...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#20
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
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