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https://www.readbyqxmd.com/read/28432778/cross-species-studies-of-cognition-relevant-to-drug-discovery-a-translational-approach
#1
REVIEW
T W Robbins
This Review advances the case that bidirectional, cross-species translation of findings from experimental animals to and from humans is an important strategy for drug discovery. Animal models of mental disorders require appropriate behavioural or cognitive outcome variables that can be generalized cross-species. One example is the treatment of impulsive behaviour in attention deficit hyperactivity disorder (ADHD) with stimulant drugs. Performance on the stop signal reaction task as an index of impulsivity is improved both in healthy human volunteers and in patients with adult ADHD by stimulant drugs and also by the selective noradrenergic reuptake blocker atomoxetine...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432010/exposure-to-an-enriched-environment-facilitates-motor-recovery-and-prevents-short-term-memory-impairment-and-reduction-of-striatal-bdnf-in-a-progressive-pharmacological-model-of-parkinsonism-in-mice
#2
Clarissa L C Campêlo, José R Santos, Anatildes F Silva, Aline L Dierschnabel, André Pontes, Jeferson S Cavalcante, Alessandra M Ribeiro, Regina H Silva
Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced PD. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of PD in mice...
April 18, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#3
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28429453/tolcapone-induces-oxidative-stress-leading-to-apoptosis-and-inhibition-of-tumor-growth-in-neuroblastoma
#4
Tyler Maser, Maria Rich, David Hayes, Ping Zhao, Abhinav B Nagulapally, Jeffrey Bond, Giselle Saulnier Sholler
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis...
April 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28429275/tgf-%C3%AE-1-neuroprotection-via-inhibition-of-microglial-activation-in-a-rat-model-of-parkinson-s-disease
#5
Xiao Chen, Zhan Liu, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
Transforming growth factor (TGF)-β1 is a pleiotropic cytokine with immunosuppressive and anti-inflammatory properties. Recently we have shown that TGF-β1 pretreatment in vitro protects against 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neuronal loss that characterizes in Parkinson's disease (PD). Herein, we aimed to demonstrate that TGF-β1 administration in vivo after MPP(+) toxicity has neuroprotection that is achieved by a mediation of microglia. A rat model of PD was prepared by injecting MPP(+) unilaterally in the striatum...
April 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28428907/palliative-care-in-huntington-disease-personal-reflections-and-a-review-of-the-literature
#6
REVIEW
Christopher G Tarolli, Amy M Chesire, Kevin M Biglan
BACKGROUND: Huntington disease is a fatal, autosomal dominant, neurodegenerative disorder manifest by the triad of a movement disorder, behavioral disturbances, and dementia. At present, no curative or disease modifying therapies exist for the condition and current treatments are symptomatic. Palliative care is an approach to care that focuses on symptom relief, patient and caregiver support, and end of life care. There is increasing evidence of the benefit of palliative care throughout the course of neurodegenerative conditions including Parkinson disease and amyotrophic lateral sclerosis...
2017: Tremor and Other Hyperkinetic Movements
https://www.readbyqxmd.com/read/28428563/a-sublethal-dose-of-a-neonicotinoid-insecticide-disrupts-visual-processing-and-collision-avoidance-behaviour-in-locusta-migratoria
#7
Rachel H Parkinson, Jacelyn M Little, John R Gray
Neonicotinoids are known to affect insect navigation and vision, however the mechanisms of these effects are not fully understood. A visual motion sensitive neuron in the locust, the Descending Contralateral Movement Detector (DCMD), integrates visual information and is involved in eliciting escape behaviours. The DCMD receives coded input from the compound eyes and monosynaptically excites motorneurons involved in flight and jumping. We show that imidacloprid (IMD) impairs neural responses to visual stimuli at sublethal concentrations, and these effects are sustained two and twenty-four hours after treatment...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428137/jwa-antagonizes-paraquat-induced-neurotoxicity-via-activation-of-nrf2
#8
Xue Zhao, Rihua Wang, Jianping Xiong, Donglin Yan, Aiping Li, Shouyu Wang, Jin Xu, Jianwei Zhou
Paraquat (PQ), a widely used environmental toxin in agriculture, contributes to the onset and progression of Parkinson's disease (PD) by damaging neurons. The JWA gene, also known as ARL6IP5, exerts a protective effect on degenerating dopamine (DA) neurons. However, the roles of JWA in PQ-induced neuronal damage are still unknown. In our study, two neuronal cell lines (HT-22 and SH-SY5Y) and neuron-specific JWA knockout (JWA-nKO) and age-matched wild-type (JWA-nWT) mice were subjected to PQ treatment. The results indicate that PQ administration triggers the upregulation of JWA...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28426824/becoming-more-oneself-changes-in-personality-following-dbs-treatment-for-psychiatric-disorders-experiences-of-ocd-patients-and-general-considerations
#9
Sanneke de Haan, Erik Rietveld, Martin Stokhof, Damiaan Denys
Does DBS change a patient's personality? This is one of the central questions in the debate on the ethics of treatment with Deep Brain Stimulation (DBS). At the moment, however, this important debate is hampered by the fact that there is relatively little data available concerning what patients actually experience following DBS treatment. There are a few qualitative studies with patients with Parkinson's disease and Primary Dystonia and some case reports, but there has been no qualitative study yet with patients suffering from psychiatric disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28425730/the-relation-of-anxiety-and-cognition-in-parkinson-s-disease
#10
Gretchen O Reynolds, Kristine K Hanna, Sandy Neargarder, Alice Cronin-Golomb
OBJECTIVE: Parkinson's disease (PD) has long been conceptualized as a motor disorder, but nonmotor symptoms also manifest in the disease and significantly reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor symptoms, even in early disease stages, but the relation between these symptoms remains poorly understood. We examined self-reported anxiety and neurocognitive function, indexed by measures of executive function (set-shifting and phonemic fluency), categorical fluency, and attention/working memory...
April 20, 2017: Neuropsychology
https://www.readbyqxmd.com/read/28425238/depression-and-parkinson-disease-prevalence-temporal-relationship-and-determinants
#11
Hale Yapici Eser, Hatice Ayşe Bora, Aslı Kuruoğlu
BACKGROUND/AIM: Comorbidity of depression in Parkinson disease (PD) is a major factor that changes patients' quality of life. However, the neurobiological and sociodemographic risk factors for this comorbidity are not well studied. In this study, we aimed to define the prevalence, temporal relationship, and psychosocial and clinical determinants of depression comorbid with PD. MATERIALS AND METHODS: Fifty-five PD patients were evaluated with SCID, a data form that assessed sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the Apathy Evaluation Scale...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424899/a-polysomnographic-study-in-parkinsonian-patients-treated-with-intestinal-levodopa-infusion
#12
Maurizio Zibetti, Alberto Romagnolo, Aristide Merola, Lorenzo Priano, Elisa Montanaro, Serena Angrisano, Antonella Tribolo, Alessandro Cicolin, Leonardo Lopiano
Sleep disorders are very common in advanced Parkinson's disease (PD) and have a significant negative impact on the quality of life of patients. Questionnaire-based studies suggest that sleep quality might improve following levodopa-carbidopa intestinal gel (LCIG) infusion. The objective of this study was to evaluate the impact of LCIG infusion and subsequent oral medication changes on polysomnography (PSG) and sleep symptoms in advanced PD patients. Eleven PD patients underwent PSG at baseline and after 3.8 ± 1...
April 19, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28424751/levodopa-responsive-parkinsonism-in-patients-with-hemochromatosis-case-presentation-and-literature-review
#13
Tarun Girotra, Abhimanyu Mahajan, Christos Sidiropoulos
Hemochromatosis is an autosomal recessive disorder which leads to abnormal iron deposition in the parenchyma of multiple organs causing tissue damage. Accumulation of iron in the brain has been postulated to be associated with several neurodegenerative diseases including Parkinson's disease. The excess iron promotes Parkin and α-synuclein aggregation in the neurons. Excess iron has also been noted in substantia nigra on MRI especially using susceptibility weighted imaging in patients with Parkinson's disease...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28424060/effects-of-a-combination-treatment-of-kd5040-and-l-dopa-in-a-mouse-model-of-parkinson-s-disease
#14
Sora Ahn, Taek-Jin Song, Seong-Uk Park, Songhee Jeon, Jongpil Kim, Joo-Young Oh, Jaehwan Jang, Sanhwa Hong, Min-A Song, Hye-Seoung Shin, Young-Rim Jung, Hi-Joon Park
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28423027/comparison-of-t2-weighted-and-qsm-contrasts-in-parkinson-s-disease-to-visualize-the-stn-with-mri
#15
Anneke Alkemade, Gilles de Hollander, Max C Keuken, Andreas Schäfer, Derek V M Ott, Johannes Schwarz, David Weise, Sonja A Kotz, Birte U Forstmann
The subthalamic nucleus (STN) plays a crucial role in the surgical treatment of Parkinson's disease (PD). Studies investigating optimal protocols for STN visualization using state of the art magnetic resonance imaging (MRI) techniques have shown that susceptibility weighted images, which display the magnetic susceptibility distribution, yield better results than T1-weighted, T2-weighted, and T2*-weighted contrasts. However, these findings are based on young healthy individuals, and require validation in elderly individuals and persons suffering from PD...
2017: PloS One
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#16
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420986/modulation-of-microglial-activity-by-rho-kinase-rock-inhibition-as-therapeutic-strategy-in-parkinson-s-disease-and-amyotrophic-lateral-sclerosis
#17
REVIEW
Anna-Elisa Roser, Lars Tönges, Paul Lingor
Neurodegenerative diseases are characterized by the progressive degeneration of neurons in the central and peripheral nervous system (CNS, PNS), resulting in a reduced innervation of target structures and a loss of function. A shared characteristic of many neurodegenerative diseases is the infiltration of microglial cells into affected brain regions. During early disease stages microglial cells often display a rather neuroprotective phenotype, but switch to a more pro-inflammatory neurotoxic phenotype in later stages of the disease, contributing to the neurodegeneration...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28420965/dopamine-a-modulator-of-circadian-rhythms-in-the-central-nervous-system
#18
REVIEW
Kirill S Korshunov, Laura J Blakemore, Paul Q Trombley
Circadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28420370/neuroprotective-effect-of-demethoxycurcumin-a-natural-derivative-of-curcumin-on-rotenone-induced-neurotoxicity-in-sh-sy-5y-neuroblastoma-cells
#19
Muthu Ramkumar, Srinivasagam Rajasankar, Veerappan Venkatesh Gobi, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ameer Kalandar, Ranganathan Chidambaram
BACKGROUND: Mitochondrial dysfunction and oxidative stress are the main toxic events leading to dopaminergic neuronal death in Parkinson's disease (PD) and identified as vital objective for therapeutic intercession. This study investigated the neuro-protective effects of the demethoxycurcumin (DMC), a derivative of curcumin against rotenone induced neurotoxicity. METHODS: SH-SY5Y neuroblastoma cells are divided into four experimental groups: untreated cells, cells incubated with rotenone (100 nM), cells treated with DMC (50 nM) + rotenone (100 nM) and DMC alone treated...
April 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28420117/metabolomic-profiling-of-the-synergistic-effects-of-melittin-in-combination-with-cisplatin-on-ovarian-cancer-cells
#20
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin-Kyu Park, Jong-Woon Jeon, Valerie A Ferro, David G Watson
Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells...
April 14, 2017: Metabolites
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