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https://www.readbyqxmd.com/read/28924920/age-dependent-alpha-synuclein-accumulation-and-phosphorylation-in-the-enteric-nervous-system-in-a-transgenic-mouse-model-of-parkinson-s-disease
#1
Chong-Bin Zhong, Qian-Qian Chen, Caroline Haikal, Wen Li, Alexander Svanbergsson, Meike Diepenbroek, Jia-Yi Li
The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model...
September 18, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28917942/in-vivo-and-in-vitro-testing-of-native-%C3%AE-conotoxins-from-the-injected-venom-of-conus-purpurascens
#2
REVIEW
Mickelene F Hoggard, Alena M Rodriguez, Herminsul Cano, Evan Clark, Han-Shen Tae, David J Adams, Tanja A Godenschwege, Frank Marí
α-Conotoxins inhibit nicotinic acetylcholine receptors (nAChRs) and are used as probes to study cholinergic pathways in vertebrates. Model organisms, such as Drosophila melanogaster, express nAChRs in their CNS that are suitable to investigate the neuropharmacology of α-conotoxins in vivo. Here we report the paired nanoinjection of native α-conotoxin PIA and two novel α-conotoxins, PIC and PIC[O7], from the injected venom of Conus purpurascens and electrophysiological recordings of their effects on the giant fiber system (GFS) of D...
September 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28917824/parkinson-s-disease-susceptibility-variants-and-severity-of-lewy-body-pathology
#3
Michael G Heckman, Koji Kasanuki, Nancy N Diehl, Shunsuke Koga, Alexandra Soto, Melissa E Murray, Dennis W Dickson, Owen A Ross
INTRODUCTION: Meta-analyses of genome-wide association studies (GWAS) have established common genetic risk factors for clinical Parkinson's disease (PD); however, associations between these risk factors and quantitative neuropathologic markers of disease severity have not been well-studied. This study evaluated associations of nominated variants from the most recent PD GWAS meta-analysis with Lewy body disease (LBD) subtype (brainstem, transitional, or diffuse) and pathologic burden of LB pathology as measured by LB counts in five cortical regions in a series of LBD cases...
September 11, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#4
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28898869/disrupted-brain-network-hubs-in-subtype-specific-parkinson-s-disease
#5
Ling-Yan Ma, Xiao-Dan Chen, Yong He, Hui-Zi Ma, Tao Feng
BACKGROUND/AIMS: The topological organization of brain functional networks is impaired in Parkinson's disease (PD). However, the altered patterns of functional network hubs in different subtypes of PD are not completely understood. METHODS: 3T resting-state functional MRI and voxel-based graph-theory analysis were employed to systematically investigate the intrinsic functional connectivity patterns of whole-brain networks. We enrolled 31 patients with PD (12 tremor dominant [TD] and 19 with postural instability/gait difficulty [PIGD]) and 22 matched healthy controls...
August 25, 2017: European Neurology
https://www.readbyqxmd.com/read/28879438/do-cognition-and-other-non-motor-symptoms-decline-similarly-among-patients-with-parkinson-s-disease-motor-subtypes-findings-from-a-5-year-prospective-study
#6
L Arie, Talia Herman, S Shema-Shiratzky, N Giladi, J M Hausdorff
Among patients with Parkinson's disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination...
September 6, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28877102/treadmill-exercise-modifies-dopamine-receptor-expression-in-the-prefrontal-cortex-of-the-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-lesioned-mouse-model-of-parkinson-s-disease
#7
Natalie Kintz, Giselle M Petzinger, Michael W Jakowec
Parkinson's disease (PD) is the second most common neurodegenerative disorder for which there is no cure. PD is a dopamine (DA)-deficit disorder marked by progressive motor and nonmotor disturbances, including cognitive impairment. Executive function (EF) is the most common subtype of cognitive impairment in PD and consists of deficits in number of processes including behavioral flexibility. The prefrontal cortex (PFC) is an important brain region subserving EF. Furthermore, DA plays a key neuromodulatory role in the PFC and altered DA neurotransmission is believed to contribute toward EF deficits in PD...
September 4, 2017: Neuroreport
https://www.readbyqxmd.com/read/28875553/human-brain-imaging-of-nicotinic-acetylcholine-%C3%AE-4%C3%AE-2-receptors-using-18-f-nifene-selectivity-functional-activity-toxicity-aging-effects-gender-effects-and-extrathalamic-pathways
#8
Jogeshwar Mukherjee, Patrick J Lao, Tobey J Betthauser, Gurleen K Samra, Min-Liang Pan, Ishani H Patel, Christopher Liang, Raju Metherate, Bradley T Christian
Nicotinic acetylcholinergic receptors (nAChR's) have been implicated in several brain disorders, including addiction, Parkinson's disease, Alzheimer's disease and schizophrenia. Here we report in vitro selectivity and functional properties, toxicity in rats, in vivo evaluation in humans, and comparison across species of [(18) F]Nifene, a fast acting PET imaging agent for α4β2* nAChRs. Nifene had subnanomolar affinities for hα2β2 (0.34 nM), hα3β2 (0.80 nM) and hα4β2 (0.83 nM) nAChR but weaker (27 to 219 nM) for hβ4 nAChR subtypes and 169 nM for hα7 nAChR...
September 5, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28867345/a-pitx3-egfp-reporter-line-reveals-connectivity-of-dopamine-and-non-dopamine-neuronal-subtypes-in-grafts-generated-from-human-embryonic-stem-cells
#9
Jonathan C Niclis, Carlos W Gantner, Cameron P J Hunt, Jessica A Kauhausen, Jennifer C Durnall, John M Haynes, Colin W Pouton, Clare L Parish, Lachlan H Thompson
Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28861502/cannabinoids-in-parkinson-s-disease
#10
REVIEW
Mario Stampanoni Bassi, Andrea Sancesario, Roberta Morace, Diego Centonze, Ennio Iezzi
The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2). In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors)...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28860330/recent-advances-in-neuropathology-biomarkers-and-therapeutic-approach-of-multiple-system-atrophy
#11
REVIEW
Shunsuke Koga, Dennis W Dickson
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively...
August 31, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28855402/polycystic-kidney-disease-is-significantly-associated-with-dementia-risk
#12
Tung-Min Yu, Ya-Wen Chuang, Kuo-Ting Sun, Mei-Ching Yu, Shiang-Cheng Kung, Brian K Lee, Shih-Ting Huang, Cheng-Hsu Chen, Cheng-Li Lin, Chia-Hung Kao
OBJECTIVE: Data on the risk of neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD), in patients with polycystic kidney disease (PKD) are lacking. METHODS: A total of 4,229 patients who were aged ≥20 years and had received a diagnosis of PKD were included in the PKD cohort. For each PKD case identified, 1 participant aged ≥20 years without a history of PKD, dementia, or PD was selected from the comparison cohort. For each patient with PKD, the corresponding controls were selected 1:1 on the basis of the nearest propensity score calculated using logistic regression...
August 30, 2017: Neurology
https://www.readbyqxmd.com/read/28844618/impact-of-pain-and-pain-subtypes-on-the-quality-of-life-of-patients-with-parkinson-s-disease
#13
Seong-Min Choi, Byeong C Kim, Hyun-Jung Jung, Geum-Jin Yoon, Kyung Wook Kang, Kang-Ho Choi, Joon-Tae Kim, Seung-Han Lee, Man-Seok Park, Myeong-Kyu Kim, Ki-Hyun Cho
Pain is a frequent and troublesome non-motor symptom of Parkinson's disease (PD) and has a negative impact on quality of life (QoL). The aim of this study was to investigate the relative impact of pain or a specific pain subtype on the QoL of patients with PD. We included 161 patients with PD. Pain was assessed using the patients' descriptions, a structured interview, and a detailed neurological examination. QoL was assessed using the 39-item Parkinson's Disease Questionnaire (PDQ-39). One hundred and twenty (74...
August 24, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28843020/clinicopathologic-discrepancies-in-a-population-based-incidence-study-of-parkinsonism-in-olmsted-county-1991-2010
#14
Pierpaolo Turcano, Michelle M Mielke, Keith A Josephs, James H Bower, Joseph E Parisi, Bradley F Boeve, Rodolfo Savica
OBJECTIVE: The purpose of this study was to examine the discrepancies between the clinical diagnosis of parkinsonism and neuropathological findings in a population-based cohort with parkinsonian disorders. BACKGROUND: The specific clinical diagnosis of parkinsonism is challenging, and definite confirmation requires neuropathological evaluation. Currently, autopsies are seldom performed, and most brain autopsies represent atypical or diagnostically unresolved cases...
August 26, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28831764/motor-impairment-and-compensation-in-a-hemiparkinsonian-rat-model-correlation-between-dopamine-depletion-severity-cerebral-metabolism-and-gait-patterns
#15
Elena Kordys, Nadine Apetz, Katharina Schneider, Eilidh Duncan, Beatriz Büschbell, Cathrin Rohleder, Michael Sué, Alexander Drzezga, Bernd Neumaier, Lars Timmermann, Heike Endepols
BACKGROUND: In Parkinson's disease (PD), cerebral dopamine depletion is associated with PD subtype-specific metabolic patterns of hypo- and hypermetabolism. It has been hypothesised that hypometabolism reflects impairment, while hypermetabolism may indicate compensatory activity. In order to associate metabolic patterns with pathophysiological and compensatory mechanisms, we combined resting state [(18)F]FDG-PET (to demonstrate brain metabolism in awake animals), [(18)F]FDOPA-PET (dopamine depletion severity) and gait analysis in a unilateral 6-hydroxydopamine rat model...
August 23, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28805581/nonmotor-parkinson-s-and-future-directions
#16
Nataliya Titova, K Ray Chaudhuri
Nonmotor symptoms (NMS) of Parkinson's disease (PD) are integral to the condition largely regarded as a motor syndrome. A range of NMS underpin the prodromal stage of Parkinson's and are present with variable frequency, range, and nature across the whole journey of a patient with Parkinson's from the onset of the motor disease to palliative stage. These symptoms also are key determinants of quality of life of the patient as well as the carer. Despite this, recognition management and focused treatment of NMS of PD remain poor...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805572/personalized-medicine-and-nonmotor-symptoms-in-parkinson-s-disease
#17
Nataliya Titova, K Ray Chaudhuri
Parkinson's disease (PD) is a multineurotransmitter dysfunction related disorder resulting in a range of motor and nonmotor symptoms. Phenotypic heterogeneity is pronounced in PD and nonmotor symptoms dominant subtypes have been described. These endophenotypes may be underpinned by considerable nondopaminergic dysfunction; however, conventional treatment of PD continues to be mostly reliant on dopamine replacement strategy or manipulation of brain dopaminergic pathways. Consequently, treatment of many nondopaminergic nonmotor and some motor symptoms remains a key unmet need...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805571/palliative-care-and-nonmotor-symptoms-in-parkinson-s-disease-and-parkinsonism
#18
Nataliya Titova, K Ray Chaudhuri
The term palliative care (PC) is defined as a collection of interventions and strategies that helps to improve and sustain the quality of life of patients and caregivers in situations and scenarios associated with life-threatening illness. This is usually implemented by means of early identification and treatment of relevant motor and nonmotor issues such as pain, sleep, and autonomic dysfunction, dementia, and depression. In addition, a holistic PC program also includes delivery of physical, psychosocial, and spiritual support...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805569/speech-voice-and-communication
#19
Julia A Johnson
Communication changes are an important feature of Parkinson's and include both motor and nonmotor features. This chapter will cover briefly the motor features affecting speech production and voice function before focusing on the nonmotor aspects. A description of the difficulties experienced by people with Parkinson's when trying to communicate effectively is presented along with some of the assessment tools and therapists' treatment options. The idea of clinical heterogeneity of PD and subtyping patients with different communication problems is explored and suggestions are made on how this may influence clinicians' treatment methods and choices so as to provide personalized therapy programmes...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802941/the-epidemiology-of-nonmotor-symptoms-in-parkinson-s-disease-cohort-and-other-studies
#20
Elena Katunina, Nataliya Titova
Nonmotor symptoms (NMS) of Parkinson's disease (PD) were recognized by James Parkinson himself and are now considered to be an integral part of PD. While clinical assessment had focused on prevalence and severity of individual NMS such as dementia and depression, work in the last decade has concentrated on global or holistic assessment of NMS using validated tools such as the NMS questionnaire and NMS scale. These studies from cohorts of varying sizes have allowed comparison of NMS across different disease stages, duration, age, and ethnicity in PD...
2017: International Review of Neurobiology
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