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https://www.readbyqxmd.com/read/28648742/polo-like-kinase-2-modulates-%C3%AE-synuclein-protein-levels-by-regulating-its-mrna-production
#1
Rikke H Kofoed, Jin Zheng, Nelson Ferreira, Søren Lykke-Andersen, Mauro Salvi, Cristine Betzer, Lasse Reimer, Torben Heick Jensen, Karina Fog, Poul H Jensen
Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies. In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein...
June 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28592329/autoimmune-antibody-decline-in-parkinson-s-disease-and-multiple-system-atrophy-a-step-towards-immunotherapeutic-strategies
#2
Tomasz Brudek, Kristian Winge, Jonas Folke, Søren Christensen, Karina Fog, Bente Pakkenberg, Lars Østergaard Pedersen
BACKGROUND: Parkinson's' disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss causes problems with movement, balance and/or autonomic functions. Naturally occurring autoantibodies (NAbs) play potentially an important role in clearing or/and blocking circulating pathological proteins. Little is known about the functional properties of anti-α-synuclein NAbs in PD and MSA, and there have been opposing reports regarding their plasma concentrations in these disorders...
June 7, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28529730/effect-of-low-versus-high-frequency-stimulation-on-freezing-of-gait-and-other-axial-symptoms-in-parkinson-patients-with-bilateral-stn-dbs-a-mini-review
#3
REVIEW
Tao Xie, Mahesh Padmanaban, Lisa Bloom, Ellen MacCracken, Breanna Bertacchi, Abraham Dachman, Peter Warnke
Some studies have shown that low frequency stimulation (LFS, most commonly 60 Hz), compared to high frequency stimulation (HFS, most commonly 130 Hz), has beneficial effects, short-term or even long-term, on improving freezing of gait (FOG) and other axial symptoms, including speech and swallowing function, in Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN DBS). However, other studies failed to confirm this. It seems not clear what determines the difference in response to LFS...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28509934/the-role-of-the-prefrontal-cortex-in-freezing-of-gait-in-parkinson-s-disease-insights-from-a-deep-repetitive-transcranial-magnetic-stimulation-exploratory-study
#4
Moria Dagan, Talia Herman, Anat Mirelman, Nir Giladi, Jeffrey M Hausdorff
Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson's disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators...
May 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28382420/cerebellar-theta-burst-stimulation-does-not-improve-freezing-of-gait-in-patients-with-parkinson-s-disease
#5
Arno M Janssen, Moniek A M Munneke, Jorik Nonnekes, Thomas van der Kraan, Alice Nieuwboer, Ivan Toni, Anke H Snijders, Bastiaan R Bloem, Dick F Stegeman
Freezing of gait (FOG) in Parkinson's disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions...
May 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28279773/deep-brain-stimulation-of-pedunculopontine-nucleus-for-postural-instability-and-gait-disorder-after-parkinson-disease-a-meta-analysis-of-individual-patient-data
#6
Jia-Wei Wang, Yu-Qing Zhang, Xiao-Hua Zhang, Yun-Peng Wang, Ji-Ping Li, Yong-Jie Li
BACKGROUND: Postural instability and gait disorder (PIGD) in Parkinson disease (PD) has been a great challenge in clinical practice because PIGD is closely linked to major morbidity and mortality in PD. Pedunculopontine nucleus (PPN) has been considered as a potential promising target for deep brain stimulation (DBS) in the treatment of PIGD. A meta-analysis of individual patient data was performed to assess the effects of PPN DBS on PIGD in patients with PD and explore the factors predicting good outcome...
June 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28244662/gluten-induced-cognitive-impairment-brain-fog-in-coeliac-disease
#7
REVIEW
Gregory W Yelland
Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as "brain fog," are yet to be formally recognized as a medical or psychological condition...
March 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28237843/characterization-of-energy-and-neurotransmitter-metabolism-in-cortical-glutamatergic-neurons-derived-from-human-induced-pluripotent-stem-cells-a-novel-approach-to-study-metabolism-in-human-neurons
#8
Blanca I Aldana, Yu Zhang, Maria Fog Lihme, Lasse K Bak, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude, Helle S Waagepetersen
Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography...
June 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28193533/effect-of-dual-mode-and-dual-site-noninvasive-brain-stimulation-on-freezing-of-gait-in-patients-with-parkinson-disease
#9
Won Hyuk Chang, Min Soo Kim, Eunhee Park, Jin Whan Cho, Jinyoung Youn, Yun Kwan Kim, Yun-Hee Kim
OBJECTIVE: To investigate the effect of dual-mode noninvasive brain stimulation (NIBS) with high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex of the lower leg and anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex compared with rTMS alone in patients with Parkinson disease (PD) with freezing of gait (FOG). DESIGN: Randomized, double-blind, controlled study. SETTING: Outpatient rehabilitation clinics...
February 11, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28095387/mri-of-cerebellar-infarction
#10
Laurens J L De Cocker, Karl-Olof Lövblad, Jeroen Hendrikse
BACKGROUND: MRI is the imaging modality of choice for diagnosing brain infarction. Because of few or atypical clinical symptoms and a relatively low sensitivity of CT scans, many cerebellar infarctions may be detected only with MRI. With adequate recognition of cerebellar infarction on MRI and prompt initiation or optimisation of preventive therapeutic measures, more dramatic strokes may be avoided in selected cases. SUMMARY: We first briefly review the clinical presentation of cerebellar infarctions, followed by a short refresher on cerebellar anatomy and pathophysiological mechanisms of cerebellar infarcts...
2017: European Neurology
https://www.readbyqxmd.com/read/27933449/clearing-the-fog-a-review-of-the-effects-of-dietary-omega-3-fatty-acids-and-added-sugars-on-chemotherapy-induced-cognitive-deficits
#11
REVIEW
Tonya S Orchard, Monica M Gaudier-Diaz, Kellie R Weinhold, A Courtney DeVries
Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27766724/effect-of-high-frequency-subthalamic-neurostimulation-on-gait-and-freezing-of-gait-in-parkinson-s-disease-a-systematic-review-and-meta-analysis
#12
REVIEW
C Schlenstedt, A Shalash, M Muthuraman, D Falk, K Witt, G Deuschl
The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no...
January 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/27651150/investigating-motor-initiation-and-inhibition-deficits-in-patients-with-parkinson-s-disease-and-freezing-of-gait-using-a-virtual-reality-paradigm
#13
Matthew J Georgiades, Moran Gilat, Kaylena A Ehgoetz Martens, Courtney C Walton, Patrick G Bissett, James M Shine, Simon J G Lewis
Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD) that is associated with deficits in motor initiation and inhibition. Understanding of underlying neurobiological mechanisms has been limited by difficulties in eliciting and objectively characterizing such gait phenomena in the clinical setting. However, recent work suggests that virtual reality (VR) techniques might offer the potential to study motor control. This study utilized a VR paradigm to explore deficits in motor initiation and stopping performance, including stop failure in PD patients with (Freezers, 31) and without (Non-Freezers, 23) FOG, and healthy age-matched Controls (15)...
November 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27649270/physiology-of-freezing-of-gait
#14
REVIEW
Anke H Snijders, Kaoru Takakusaki, Bettina Debu, Andres M Lozano, Vibhor Krishna, Alfonso Fasano, Tipu Z Aziz, Stella M Papa, Stewart A Factor, Mark Hallett
Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG...
November 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27599588/freezing-of-gait-in-parkinson-s-disease-from-pathophysiology-to-emerging-therapies
#15
Alberto Cucca, Milton C Biagioni, Jori E Fleisher, Shashank Agarwal, Andre Son, Pawan Kumar, Miroslaw Brys, Alessandro Di Rocco
Freezing of gait (FOG) is 'an episodic inability to generate effective stepping in the absence of any known cause other than parkinsonism or high level gait disorders'. FOG is one of the most disabling symptoms in Parkinson's disease, especially in its more advanced stages. Early recognition is important as FOG is related to higher fall risk and poorer prognosis. Although specific treatments are still elusive, there have been recent advances in the development of new therapeutic approaches. The aim of this review is to present the latest knowledge regarding the phenomenology, pathogenesis, diagnostic assessment and conventional treatment of FOG in Parkinson's disease...
October 2016: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/27596958/induced-pluripotent-stem-cell-derived-neurons-for-the-study-of-spinocerebellar-ataxia-type-3
#16
Susanne K Hansen, Tina C Stummann, Helena Borland, Lis F Hasholt, Zeynep Tümer, Jørgen E Nielsen, Mikkel A Rasmussen, Troels T Nielsen, Justus C A Daechsel, Karina Fog, Poul Hyttel
The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method and the resulting SCA3 iPSCs were differentiated into neurons. These neuronal lines harbored the disease causing mutation, expressed comparable levels of several neuronal markers and responded to the neurotransmitters, glutamate/glycine, GABA and acetylcholine...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27595545/experiences-and-concerns-of-patients-with-recurrent-attacks-of-acute-hepatic-porphyria-a-qualitative-study
#17
Hetanshi Naik, Mikayla Stoecker, Saskia C Sanderson, Manisha Balwani, Robert J Desnick
BACKGROUND: The acute hepatic porphyrias (AHPs) are rare inborn errors of heme biosynthesis, characterized clinically by life-threatening acute neurovisceral attacks. Patients with recurrent attacks have a decreased quality of life (QoL); however, no interactive assessment of these patients' views has been reported. We conducted guided discussions regarding specific topics, to explore patients' disease experience and its impact on their lives. METHODS: Sixteen AHP patients experiencing acute attacks were recruited to moderator-led online focus groups...
November 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27579212/5-ht2a-receptor-binding-in-the-frontal-cortex-of-parkinson-s-disease-patients-and-alpha-synuclein-overexpressing-mice-a-postmortem-study
#18
Nadja Bredo Rasmussen, Mikkel Vestergaard Olesen, Tomasz Brudek, Per Plenge, Anders Bue Klein, Jenny E Westin, Karina Fog, Gitta Wörtwein, Susana Aznar
The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations...
2016: Parkinson's Disease
https://www.readbyqxmd.com/read/27534783/-impact-of-treatments-to-improve-cognitive-function-and-quality-of-life-on-cancer-patients-with-carcinoma-of-the-testes
#19
REVIEW
L Vasiľková
BACKGROUND: Testicular cancer is one of the most common and most treatable cancers in men aged 15-49 years. The high survival rates mean that it is essential to maintain quality of life and minimize adverse effects associated with treatment. Both malignant tumors and the modalities used to treatment them can have adverse effects from both a psychosocial and a neurocognitive function perspective. Recently, attention has focused on the negative impact of the disease and its treatment on the brain and on cognitive function, which can result in a form of neurocognitive dysfunction known as "chemo brain" or "chemo fog"...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27272226/cognition-and-the-menopause-transition
#20
Pauline M Maki, Victor W Henderson
Complaints about forgetfulness, "brain fog," and difficulty concentrating are common in women transitioning through menopause. Women with these cognitive complaints often express concern about whether these problems are normal, related to menopause, or represent a symptom of Alzheimer disease or another serious cognitive disorder. In this Practice Pearl, we provide a brief summary of the scientific literature on the frequency of cognitive complaints in midlife women, the validity of complaints in relation to performance on standardized cognitive tests, and the influence of menopause on cognitive performance...
July 2016: Menopause: the Journal of the North American Menopause Society
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