Alternative excitotoxic hypotheses

Albin, Roger L.; Greenamyre, J. Timothy

doi:10.1212/wnl.42.4.733

Cited by 574Asthma and respiratory diseasesOccupational exposure and asthmaRespiratory and Cough-Related Research

Alternative excitotoxic hypotheses

Albin, Roger L., Greenamyre, J. Timothy·1992·Neurology

DOI 10.1212/wnl.42.4.733

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Abstract

It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time. To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5–11.5 years and analysed using latent transition analysis. In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52–60%), 2) atopic, few symptoms (3–21%), 3) nonatopic, asthma and rhinitis symptoms (13–35%), and 4) atopic, asthma and rhinitis symptoms (2–14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41–46%), 2) atopic, no respiratory disease (23–33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8–12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood. This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.

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Damage to glutamatergic neurons, particularly cell bodies and neurites in layers III and IV of the neocortex, and to glutamatergically-innervated cortical and hippocampal neurons, is particularly evident in AD brain.
“Damage to glutamatergic neurons, in particular cell bodies and neurites in layers III and IV of the neocortex, together with damage to glutamatergically-innervated cortical and hippocampal neurons, are particularly evident in AD brain (Albin and Greenamyre 1992).”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Albin and Greenamyre 1992

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Implants of Encapsulated Human CNTF-Producing Fibroblasts Prevent Behavioral Deficits and Striatal Degeneration in a Rodent Model of Huntington’s Disease
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“The symptoms of HD result from this selective vulnerability of neostriatal neurons, possibly because of an endogenous disequilibrium of energy metabolism and excitotoxicity (Parker et al., 1990; Albin and Greenamyre, 1992; Beal, 1992; Wallace, 1992).”
Background
Nitric Oxide Acutely Inhibits Neuronal Energy Production
Brorson, J. R., Schumacker, P. T., & Zhang, H. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-01-00147.1999 · Cited by 200 · see citing works
“…has been postulated to occur in chronic neurological conditions whereby the combination of underlying defects in energy metabolism in neurons, combined with the stress of ongoing glutamate receptor activation, gradually produces neuronal damage or death (Albin and Greenamyre, 1992; Beal, 1995).”
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Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate
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Chemotherapy for the Brain: The Antitumor Antibiotic Mithramycin Prolongs Survival in a Mouse Model of Huntington's Disease
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“Because mitochondrial dysfunction and impaired energy me - tabolism has been implicated in HD pathogenesis ( Albin and Greenamyre , 1992 ; Beal , 1992 ) , it was also necessary to rule out the possibility that mithramycin protects by modulating MPT .”
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Mutant Huntingtin Enhances Excitotoxic Cell Death
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“Neurodegeneration in HD has been strongly linked to an excitotoxic mechanism mediated through NMDA receptors, either directly or as a secondary event associated with altered metabolism (DiFiglia, 1990; Beal et al., 1991, 1993; Albin and Greenmayre, 1992).”
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3-Nitropropionic acid animal model and Huntington' s disease
Borlongan, C. V., Koutouzis, T. K., & Sanberg, P. R. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00027-9 · Cited by 194 · see citing works
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Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate
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Subtype‐Specific Enhancement of NMDA Receptor Currents by Mutant Huntingtin
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Cystamine Inhibits Caspase Activity
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Alzheimer’s disease: Targeting the glutamatergic system
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Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity
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“…AD are believed not necessarily to depend only on increased glutamate levels per se, but also on increased receptor sensitivity and over-activation by resting levels of glutamate (Albin & Greenamyre, 1992), followed by release of endogenous glutamate (Henneberry et al., 1989; Choi & Rothman, 1990).”
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Tissue transglutaminase: a possible role in neurodegenerative diseases
Lesort, M. J., Tucholski, J., Miller, M. L., & Johnson, G. V. W. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00052-0 · Cited by 174 · see citing works
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“Further specificity of neuronal destruction is evidenced by the targeting of specific cell types within these regions (Hyman et al., 1984; Greenamyre and Young, 1989; Albin and Greenamyre, 1992).”
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Neurodegeneration in Methylmalonic Aciduria Involves Inhibition of Complex II and the Tricarboxylic Acid Cycle, and Synergistically Acting Excitotoxicity
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The relationship between excitotoxicity and oxidative stress in the central nervous system
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Selective Neuronal Degeneration in Huntington's Disease
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Calpain Is a Major Cell Death Effector in Selective Striatal Degeneration InducedIn Vivoby 3-Nitropropionate: Implications for Huntington's Disease
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Update on Parkinson Disease
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Heterogeneous Topographic and Cellular Distribution of Huntingtin Expression in the Normal Human Neostriatum
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“Another hypothesis as to the pathogenesis of HD is that an impairment of energy metabolism may play a critical role by rendering neurons vulnerable to excitotoxicity (Albin and Greenamyre, 1992; Beal, 1992, 1994, 1995).”
Background
Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS
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Mitochondrial Dysfunction in Parkinson's Disease
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“Several mechanisms for excitotoxicity in neurodegenerative conditions have been proposed [50, 51].”
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Genetics and molecular biology of Huntington's disease
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Self-citation
Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat
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Authors: Albin, R. L., & Greenamyre, J. T.
Affiliations: University of Michigan (US)
University of Rochester (US)
ORCID: Albin, Roger L.
Greenamyre, J. Timothy
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1992-04
Volume: 42
Issue: 4
Pages: 733-733
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.42.4.733
OpenAlex: W2058176457
Cited by: 574
References: 0
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 18 · 2021: 4 · 2020: 12 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 12 · 2012: 16
FWCI: 14.01
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k08ns001300-03, 5k08ns001487-03)
National Institute of Neurological Disorders and Stroke (NS01300, NS 01487)
Topics: Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
Keywords: asthma phenotypes, childhood asthma, asthma heterogeneity, phenotype transition, atopy, rhinitis, airway hyperresponsiveness, exhaled nitric oxide, wheezing, latent transition analysis, birth cohort
MeSH terms: Acute Disease, Amino Acids, Chronic Disease, Humans, Models, Neurological, Nerve Degeneration, Nervous System Diseases, Neurology, Neurotoxins, Receptors, Cell Surface, Receptors, Amino Acid

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