Increased Amyloid Protein Precursor and Apolipoprotein E Immunoreactivity in the Selectively Vulnerable Hippocampus Following Transient Forebrain Ischemia in Gerbils

Hall, Edward D.; Oostveen, Jo A.; Dunn, Edwige; Carter, Donald B.

doi:10.1006/exnr.1995.1062

Cited by 110 publications

(72 citation statements)

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“…33 ApoE also has the ability to protect neurons from oxidative injury. 34 Finally, in the gerbil, apoE is selectively expressed in vulnerable areas of the hippocampus after global ischemia, 35 and apoE accumulates in postischemic neurons in the rat. 36,37 This suggests a potential active role of apoE in response to events initiated during the ischemic insult.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse

Sheng

Laskowitz

Mackensen

et al. 1999

Stroke

108

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Background and Purpose-Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. Methods-ApoE deficient (nϭ16) and wild type (nϭ17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by 14 C-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. Results-The percentage of dead hippocampal CA1 neurons (meanϮSD) was greater in the apoE-deficient group (apoE deficientϭ67Ϯ30%; wild typeϭ37Ϯ33%; Pϭ0.011). A similar pattern was observed in the caudoputamen (Pϭ0.002) and neocortex (Pϭ0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. Conclusions-ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia. (Stroke. 1999;30;1118 -1124.)

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Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse

Sheng

Laskowitz

Mackensen

et al. 1999

Stroke

108

View full text Add to dashboard Cite

show abstract

“…Ischemia, hypoglycemia, and traumatic brain injury, a condition that has been shown to put neurons under metabolic stress (Xiong et al, 1997), all up-regulate A␤PP and its mRNA in animal models and culture systems (Hall et al, 1995;Jendroska et al, 1995;Yokota et al, 1996;Shi et al, 1997;Murakami et al, 1998). Not only does energy deficiency and Ca(II) dysregulation promote A␤PP expression, they also route the metabolism of A␤PP from the nonamyloidogenic to the amyloidogenic pathway.…”

Section: Amyloid-␤ and Alzheimer Disease: The Alternate Hypothesismentioning

confidence: 99%

Amyloid-β in Alzheimer Disease: The Null versus the Alternate Hypotheses

Lee¹,

Zhu²,

Castellani³

et al. 2007

The Journal of Pharmacology and Experimental Therapeutics

134

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“…Ab is the g-secretase cleavage product of the amyloid precursor protein (APP; Checler, 1995;Selkoe, 1991;Haass et al, 1992) and in its mature form consists of 42 amino acid residues (Ab (1±42) ; Glenner & Wong, 1984). Noxious conditions, such as in¯ammation (Yan et al, 1996), metabolic disturbances (Hall et al, 1995) and excitotoxic stimulation , selectively alter processing of APP, modify intracellular Ab catabolism (Iwata et al 2000) and result in the enhanced generation of full-length Ab. Ample experimental evidence indicates that Ab affects neural functions in a bi-modal manner (Yankner et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

β‐Amyloid neurotoxicity is mediated by a glutamate‐triggered excitotoxic cascade in rat nucleus basalis

Harkany

Ábrahám

Timmerman

et al. 2000

Eur J of Neuroscience

261

151

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β-Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis Harkany, T.; Ábrahám, I.; Timmerman, W.; Laskay, G.; Tóth, B.; Sasvári, M.; Kónya, C.; Sebens, J.B.; Korf, Jakob; Nyakas, C. Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Harkany, T., Ábrahám, I., Timmerman, W., Laskay, G., Tóth, B., Sasvári, M., ... Luiten, P. G. M. (2000). β-Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis. European Journal of Neuroscience, 12, 2735-2745. CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. SummaryWhereas a cardinal role for b-amyloid protein (Ab) has been postulated as a major trigger of neuronal injury in Alzheimer's disease, the pathogenic mechanism by which Ab deranges nerve cells remains largely elusive. Here we report correlative in vitro and in vivo evidence that an excitotoxic cascade mediates Ab neurotoxicity in the rat magnocellular nucleus basalis (MBN). In vitro application of Ab to astrocytes elicits rapid depolarization of astroglial membranes with a concomitant inhibition of glutamate uptake. In vivo Ab infusion by way of microdialysis in the MBN revealed peak extracellular concentrations of excitatory amino acid neurotransmitters within 20±30 min. Ab-triggered extracellular elevation of excitatory amino acids coincided with a signi®cantly enhanced intracellular accumulation of Ca 2+ in the Ab injection area, as was demonstrated by 45 Ca 2+ autoradiography. In consequence of these acute processes delayed cell death in the MBN and persistent loss of cholinergic ®bre projections to the neocortex appear as early as 3 days following the Ab-induced toxic insult. Such a sequence of Ab toxicity was effectively antagonized by the N-methyl-D-aspartate (NMDA) receptor ligand dizocilpine maleate (MK-801). Moreover, Ab toxicity in the MBN decreases with advancing age that may be associated with the age-related loss of NMDA receptor expression in rats. In summary, the present results indicate that Ab compromises neurons of the rat MBN via an excitotoxic pathway including astroglial depolarization, extracellular glutamate accumulation, NMDA receptor activation and an intracellular Ca 2+ overload leading to cell death.

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Increased Amyloid Protein Precursor and Apolipoprotein E Immunoreactivity in the Selectively Vulnerable Hippocampus Following Transient Forebrain Ischemia in Gerbils

Cited by 110 publications

References 0 publications

Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse

Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse

Amyloid-β in Alzheimer Disease: The Null versus the Alternate Hypotheses

β‐Amyloid neurotoxicity is mediated by a glutamate‐triggered excitotoxic cascade in rat nucleus basalis

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