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https://www.readbyqxmd.com/read/29644335/neuromelanin-detection-by-magnetic-resonance-imaging-mri-and-its-promise-as-a-biomarker-for-parkinson-s-disease
#1
REVIEW
David Sulzer, Clifford Cassidy, Guillermo Horga, Un Jung Kang, Stanley Fahn, Luigi Casella, Gianni Pezzoli, Jason Langley, Xiaoping P Hu, Fabio A Zucca, Ioannis U Isaias, Luigi Zecca
The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29615733/locus-coeruleus-complex-of-the-family-delphinidae
#2
Simona Sacchini, Manuel Arbelo, Cristiano Bombardi, Antonio Fernández, Bruno Cozzi, Yara Bernaldo de Quirós, Pedro Herráez
The locus coeruleus (LC) is the largest catecholaminergic nucleus and extensively projects to widespread areas of the brain and spinal cord. The LC is the largest source of noradrenaline in the brain. To date, the only examined Delphinidae species for the LC has been a bottlenose dolphin (Tursiops truncatus). In our experimental series including different Delphinidae species, the LC was composed of five subdivisions: A6d, A6v, A7, A5, and A4. The examined animals had the A4 subdivision, which had not been previously described in the only Delphinidae in which this nucleus was investigated...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29520900/neuromelanin-sensitive-mri-features-of-the-substantia-nigra-and-locus-coeruleus-in-de-novo-parkinson-s-disease-and-its-phenotypes
#3
Jian Wang, Yuanfang Li, Zhen Huang, Wenbing Wan, Yong Zhang, Changpeng Wang, Xiaoqin Cheng, Fang Ye, Kai Liu, Guoqiang Fei, Mengsu Zeng, Lirong Jin
BACKGROUND: Neuromelanin of the brainstem, which is considered a marker of neurodegeneration in Parkinson's disease (PD), can be detected by T1-weighted neuromelanin-sensitive magnetic resonance imaging (NM-MRI). We aimed to investigate the NM-MRI features of de novo PD and to determine whether these features are associated with motor and non-motor symptoms in de novo PD patients. METHODS: Fifty-one patients with de novo PD (Hoehn and Yahr stage 1-2) and 28 healthy controls were recruited...
March 9, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29498540/quantifying-changes-in-nigrosomes-using-quantitative-susceptibility-mapping-and-neuromelanin-imaging-for-the-diagnosis-of-early-stage-parkinson-s-disease
#4
Hiroto Takahashi, Yoshiyuki Watanabe, Hisashi Tanaka, Masahito Mihara, Hideki Mochizuki, Tian Liu, Yi Wang, Noriyuki Tomiyama
OBJECTIVE: To quantify nigral changes with a focus on their spatial variation within the substantia nigra pars compacta (SNpc) for diagnosing early-stage Parkinson's disease (PD). METHODS: The study participants were 18 patients with early-stage PD (PD group) and 18 healthy controls (HC group) who underwent quantitative susceptibility mapping (QSM) and neuromelanin imaging. The QSM and neuromelanin values in each whole SNpc containing the entire nigrosome and dorsolateral SNpc containing nigrosome 1 were calculated...
March 2, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29440429/locus-coeruleus-integrity-in-old-age-is-selectively-related-to-memories-linked-with-salient-negative-events
#5
Dorothea Hämmerer, Martina F Callaghan, Alexandra Hopkins, Julian Kosciessa, Matthew Betts, Arturo Cardenas-Blanco, Martin Kanowski, Nikolaus Weiskopf, Peter Dayan, Raymond J Dolan, Emrah Düzel
The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29341412/3d-neuromelanin-sensitive-magnetic-resonance-imaging-of-the-substantia-nigra-in-parkinson-s-disease
#6
Shweta Prasad, Albert Stezin, Abhishek Lenka, Lija George, Jitender Saini, Ravi Yadav, Pramod Kumar Pal
BACKGROUND: To investigate the diagnostic utility of signal intensity measurement of the substantia nigra pars compacta (SNc) using three dimensional (3D) neuromelanin-sensitive 31MRI, for discrimination of patients with PD from healthy controls. METHODS: T1-weighted neuromelanin sensitive images of 16 patients with PD and 15 controls were quantitatively analyzed by placing circular 10mm2 regions of interest (ROI) over the central and lateral parts of bilateral SNc, and anterior to the cerebral aqueduct at 3 levels of the midbrain...
January 17, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29317067/nigral-depigmentation-reflects-monoamine-exhaustion-as-initial-step-to-parkinson-s-disease
#7
Thomas Müller, Willi Kohlhepp
This hypothesis discusses exposure and response to various stressors as cause for chronic neurodegeneration. Predisposing genetic and environmental factors in conjunction with exposure to exogenous and endogenous toxins cause stress, which consumes dopamine and related biogenic amines. To compensate monoamine exhaustion, conversion of endogenous levodopa to dopamine by tyrosine hydroxylase is up regulated. Concomitantly, tyrosine mediated levodopa degradation to dopaquinone is reduced. Dopaquinone is the essential precursor of neuromelanin...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29301874/locus-coeruleus-activity-strengthens-prioritized-memories-under-arousal
#8
David V Clewett, Ringo Huang, Rico Velasco, Tae-Ho Lee, Mara Mather
Recent models posit that bursts of locus ceruleus (LC) activity amplify neural gain such that limited attention and encoding resources focus even more on prioritized mental representations under arousal. Here, we tested this hypothesis in human males and females using fMRI, neuromelanin MRI, and pupil dilation, a biomarker of arousal and LC activity. During scanning, participants performed a monetary incentive encoding task in which threat of punishment motivated them to prioritize encoding of scene images over superimposed objects...
February 7, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29162523/specific-visualization-of-neuromelanin-iron-complex-and-ferric-iron-in-the-human-post-mortem-substantia-nigra-using-mr-relaxometry-at-7t
#9
Hansol Lee, Sun-Yong Baek, Se Young Chun, Jae-Hyeok Lee, HyungJoon Cho
Neuromelanin (NM) is an endogenous iron chelating molecule of pigmented neurons in the human substantia nigra (SN). Along with the increase in iron deposition, the reduction in NM-containing dopaminergic neurons and the variation of iron load on NM are generally considered to be important factors participating to pathogenesis of Parkinson's disease (PD). The aim of this study was to non-invasively delineate the spatial distributions of paramagnetic magnetic susceptibility perturbers, such as NM-iron complex and ferric iron in SN...
November 21, 2017: NeuroImage
https://www.readbyqxmd.com/read/29089976/odorants-could-elicit-repair-processes-in-melanized-neuronal-and-skin-cells
#10
REVIEW
Barbara Pavan, Alessandro Dalpiaz
The expression of ectopic olfactory receptors (ORs) in melanized cells, such as the human brain nigrostriatal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson's disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through α-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pigmentation disorders...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29047416/lessons-learned-about-f-18-av-1451-off-target-binding-from-an-autopsy-confirmed-parkinson-s-case
#11
Marta Marquié, Eline E Verwer, Avery C Meltzer, Sally Ji Who Kim, Cinthya Agüero, Jose Gonzalez, Sara J Makaretz, Michael Siao Tick Chong, Prianca Ramanan, Ana C Amaral, Marc D Normandin, Charles R Vanderburg, Stephen N Gomperts, Keith A Johnson, Matthew P Frosch, Teresa Gómez-Isla
[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas...
October 19, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29044415/morphologic-and-elemental-analysis-of-primary-melanosis-of-the-dentate-nucleus-review-and-correlation-with-neuromelanin
#12
REVIEW
Richard T Hopley, Edward Haller, Mumtaz V Rojiani, Amyn M Rojiani
Primary melanosis of the dentate nucleus is a rarely described entity with neither known cause nor definitive clinicopathologic correlation. We revisit this previously reported phenomenon by presenting one such case with a review of the pathology as well as additional investigations including elemental analysis by energy-dispersive X-ray, immunohistochemistry and electron microscopy. The lesion presented macroscopically as a sharply defined, black pigmentation that was restricted to the dentate nucleus of the cerebellum...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28958075/magnetic-resonance-imaging-biomarkers-to-assess-substantia-nigra-damage-in-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#13
Nadya Pyatigorskaya, Rahul Gaurav, Dario Arnaldi, Smaranda Leu-Semenescu, Lydia Yahia-Cherif, Romain Valabregue, Marie Vidailhet, Isabelle Arnulf, Stephane Lehéricy
Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Methods: Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping...
November 1, 2017: Sleep
https://www.readbyqxmd.com/read/28945963/the-analgesic-acetaminophen-and-the-antipsychotic-clozapine-can-each-redox-cycle-with-melanin
#14
Zülfikar Temoçin, Eunkyoung Kim, Jinyang Li, Lucia Panzella, Maria Laura Alfieri, Alessandra Napolitano, Deanna L Kelly, William E Bentley, Gregory F Payne
Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context...
December 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28943414/in-vivo-mri-assessment-of-the-human-locus-coeruleus-along-its-rostrocaudal-extent-in-young-and-older-adults
#15
Matthew J Betts, Arturo Cardenas-Blanco, Martin Kanowski, Frank Jessen, Emrah Düzel
The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from low spatial resolution along the rostrocaudal axis of the LC rendering it difficult to differentiate its integrity in caudal and rostral portions...
December 2017: NeuroImage
https://www.readbyqxmd.com/read/28912300/-18-f-av-1451-binding-in-vivo-mirrors-the-expected-distribution-of-tdp-43-pathology-in-the-semantic-variant-of-primary-progressive-aphasia
#16
W R Bevan-Jones, Thomas E Cope, P Simon Jones, Luca Passamonti, Young T Hong, Tim D Fryer, Robert Arnold, Kieren S J Allinson, Jonathan P Coles, Franklin I Aigbirhio, Karalyn Patterson, John T O'Brien, James B Rowe
INTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [(18)F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [(18)F]AV-1451...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28884232/-18-f-av-1451-binding-to-neuromelanin-in-the-substantia-nigra-in-pd-and-psp
#17
Sarah Coakeley, Sang Soo Cho, Yuko Koshimori, Pablo Rusjan, Christine Ghadery, Jinhee Kim, Anthony E Lang, Sylvain Houle, Antonio P Strafella
This study investigated binding of [(18)F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). [(18)F]AV-1451 is a positron emission tomography radiotracer designed to bind pathological tau. A post-mortem study using [(18)F]AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra. A subsequent clinical study reported a 30% decrease in [(18)F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited...
September 7, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28879408/neuromelanin-in-parkinson-s-disease-from-fenton-reaction-to-calcium-signaling
#18
REVIEW
Rainer Knörle
Neuromelanin is supposed to play a key role in the pathogenesis of Parkinson's disease. A common theory is the formation of reactive oxygen species through the Fenton reaction catalyzed by neuromelanin-bound iron ions and subsequent death of the dopaminergic cells in the substantia nigra. From a physicochemical point of view, this pathway is rather implausible: a highly reactive radical built within a powerful radical scavenger would more promptly be inactivated before it might diffuse within the cell to reach a target to exert its deleterious potential...
February 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/28763613/the-importance-of-mitophagy-in-maintaining-mitochondrial-function-in-u373mg-cells-bafilomycin-a1-restores-aminochrome-induced-mitochondrial-damage
#19
Sandro Huenchuguala, Patricia Muñoz, Juan Segura-Aguilar
Aminochrome, an orthoquinone formed during the dopamine oxidation of neuromelanin, is neurotoxic because it induces mitochondria dysfunction, protein degradation dysfunction (both autophagy and proteasomal systems), α-synuclein aggregation to neurotoxic oligomers, neuroinflammation, and oxidative and endoplasmic reticulum stress. In this study, we investigated the relationship between aminochrome-induced autophagy/lysosome dysfunction and mitochondrial dysfunction in U373MGsiGST6 cells. Aminochrome (75 μM) induces mitochondrial dysfunction as determined by (i) a significant decrease in ATP levels (70%; P < 0...
August 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28761417/on-the-role-of-endogenous-neurotoxins-and-neuroprotection-in-parkinson-s-disease
#20
REVIEW
Juan Segura-Aguilar
For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease...
June 2017: Neural Regeneration Research
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