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https://www.readbyqxmd.com/read/28241427/potential-modes-of-intercellular-%C3%AE-synuclein-transmission
#1
REVIEW
Dario Valdinocci, Rowan A W Radford, Sue Maye Siow, Roger S Chung, Dean L Pountney
Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28197821/evaluation-of-glymphatic-system-activity-with-the-diffusion-mr-technique-diffusion-tensor-image-analysis-along-the-perivascular-space-dti-alps-in-alzheimer-s-disease-cases
#2
Toshiaki Taoka, Yoshitaka Masutani, Hisashi Kawai, Toshiki Nakane, Kiwamu Matsuoka, Fumihiko Yasuno, Toshifumi Kishimoto, Shinji Naganawa
PURPOSE: The activity of the glymphatic system is impaired in animal models of Alzheimer's disease (AD). We evaluated the activity of the human glymphatic system in cases of AD with a diffusion-based technique called diffusion tensor image analysis along the perivascular space (DTI-ALPS). MATERIALS AND METHODS: Diffusion tensor images were acquired to calculate diffusivities in the x, y, and z axes of the plane of the lateral ventricle body in 31 patients. We evaluated the diffusivity along the perivascular spaces as well as projection fibers and association fibers separately, to acquire an index for diffusivity along the perivascular space (ALPS-index) and correlated them with the mini mental state examinations (MMSE) score...
February 14, 2017: Japanese Journal of Radiology
https://www.readbyqxmd.com/read/28197669/clearance-of-cerebral-a%C3%AE-in-alzheimer-s-disease-reassessing-the-role-of-microglia-and-monocytes
#3
REVIEW
Leah Zuroff, David Daley, Keith L Black, Maya Koronyo-Hamaoui
Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28196227/the-ocular-glymphatic-system-and-idiopathic-intracranial-hypertension-author-response-to-hypodense-holes-and-the-ocular-glymphatic-system
#4
Alastair K Denniston, Pearse A Keane, Anuriti Aojula, Alex J Sinclair, Susan P Mollan
No abstract text is available yet for this article.
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28196226/-hypodense-holes-and-the-ocular-glymphatic-system-author-response-black-holes-and-the-ocular-glymphatic-system
#5
Peter Wostyn, Veva De Groot, Debby Van Dam, Kurt Audenaert, Peter Paul De Deyn, Hanspeter Esriel Killer
No abstract text is available yet for this article.
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28193695/cortical-spreading-depression-closes-the-paravascular-space-and-impairs-glymphatic-flow-implications-for-migraine-headache
#6
Aaron J Schain, Agustin Melo, Andrew M Strassman, Rami Burstein
Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novel in vivo method we developed to visualize the PVS in naïve uninjected mice using 2-photon microscopy, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the paravascular space (PVS) around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28188218/focal-solute-trapping-and-global-glymphatic-pathway-impairment-in-a-murine-model-of-multiple-microinfarcts
#7
Minghuan Wang, Fengfei Ding, SaiYue Deng, Xuequn Guo, Wei Wang, Jeffrey J Iliff, Maiken Nedergaard
Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. Yet the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid beta and tau...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28129671/glymphatic-stasis-at-the-site-of-the-lamina-cribrosa-as-a-potential-mechanism-underlying-open-angle-glaucoma
#8
REVIEW
Peter Wostyn, Hanspeter Esriel Killer, Peter Paul De Deyn
The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered 'glymphatic system' in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β-amyloid, from the brain along paravascular channels...
January 27, 2017: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/28123166/lack-of-contrast-enhancement-in-a-giant-perivascular-space-of-the-basal-ganglion-on-delayed-flair-images-implications-for-the-glymphatic-system
#9
Shinji Naganawa, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka
No abstract text is available yet for this article.
January 25, 2017: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/28096295/does-selection-for-short-sleep-duration-explain-human-vulnerability-to-alzheimer-s-disease
#10
Randolph M Nesse, Caleb E Finch, Charles L Nunn
Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD...
January 16, 2017: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/28054371/review-tau-in-biofluids-relation-to-pathology-imaging-and-clinical-features
#11
Henrik Zetterberg
Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Further, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm...
January 5, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28045032/mechanical-stress-activates-nmda-receptors-in-the-absence-of-agonists
#12
Mohammad Mehdi Maneshi, Bruce Maki, Radhakrishnan Gnanasambandam, Sophie Belin, Gabriela K Popescu, Frederick Sachs, Susan Z Hua
While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca(2+) entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca(2+) influx...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27931262/glymphatic-distribution-of-csf-derived-apoe-into-brain-is-isoform-specific-and-suppressed-during-sleep-deprivation
#13
Thiyagaragan M Achariyar, Baoman Li, Weiguo Peng, Philip B Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takana, David M Holtzman, Maiken Nedergaard, Rashid Deane
BACKGROUND: Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel...
December 8, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27893874/association-of-perivascular-localization-of-aquaporin-4-with-cognition-and-alzheimer-disease-in-aging-brains
#14
Douglas M Zeppenfeld, Matthew Simon, J Douglas Haswell, Daryl D'Abreo, Charles Murchison, Joseph F Quinn, Marjorie R Grafe, Randall L Woltjer, Jeffrey Kaye, Jeffrey J Iliff
Importance: Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet the factors that render the aging brain vulnerable to these processes are unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including amyloid-β, through the brainwide network of perivascular pathways termed the glymphatic system, which may be compromised in the aging brain. Objectives: To determine whether alterations in AQP4 expression or loss of perivascular AQP4 localization are features of the aging human brain and to define their association with AD pathology...
January 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/27837334/mechanism-of-depression-as-a-risk-factor-in-the-development-of-alzheimer-s-disease-the-function-of-aqp4-and-the-glymphatic-system
#15
Maosheng Xia, Li Yang, Guangfeng Sun, Shuang Qi, Baoman Li
BACKGROUND: Many studies have indicated that a history of depression increases the risk of developing Alzheimer's disease (AD); however, the potential pathogenestic mechanism by which depression functions as a high risk factor for AD remains unknown. Recently, a "cerebral lymphatic system" referred to as "glymphatic system" has been demonstrated to be responsible for neuronal extracellular waste protein clearance via a paravascular pathway. However, the function of glymphatic pathway has not been determined in depressive disorders...
February 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27836940/spatial-model-of-convective-solute-transport-in-brain-extracellular-space-does-not-support-a-glymphatic-mechanism
#16
Byung-Ju Jin, Alex J Smith, Alan S Verkman
A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces...
December 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27789520/omega-3-polyunsaturated-fatty-acids-promote-amyloid-%C3%AE-clearance-from-the-brain-through-mediating-the-function-of-the-glymphatic-system
#17
Huixia Ren, Chuanming Luo, Yanqing Feng, Xiaoli Yao, Zhe Shi, Fengyin Liang, Jing X Kang, Jian-Bo Wan, Zhong Pei, Huanxing Su
Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27768787/-black-holes-and-the-ocular-glymphatic-system-author-response-to-the-glymphatic-system-a-new-player-in-ocular-diseases
#18
Alastair K Denniston, Pearse A Keane
No abstract text is available yet for this article.
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27768786/the-glymphatic-system-a-new-player-in-ocular-diseases
#19
Peter Wostyn, Veva De Groot, Debby Van Dam, Kurt Audenaert, Peter Paul De Deyn, Hanspeter Esriel Killer
No abstract text is available yet for this article.
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27739621/african-trypanosomes-and-brain-infection%C3%A2-%C3%A2-the-unsolved-question
#20
Stefan Mogk, Christian M Boßelmann, Celestin N Mudogo, Jasmin Stein, Hartwig Wolburg, Michael Duszenko
African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier...
October 14, 2016: Biological Reviews of the Cambridge Philosophical Society
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