In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

Stuiver, Bauke; Douma, B.R.K.; Bakker, Roel; Nyakas, Csaba; Luiten, P.G.M.

doi:10.1006/neur.1996.0022

Cited by 55 publications

(34 citation statements)

References 39 publications

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“…4A). In all experiments a 14-day survival period was used, based on previous observations (Harkany et al, 1995b;Stuiver et al, 1996;1999b International, Natick, MA, USA) was dissolved in physiological saline and administered intraperitoneally (i.p.) at a concentration of 5.0 mg/kg body weight in a total volume of 1 mL/kg body weight.…”

Section: Animals Acute Lesion Procedures and Mk-801 Administrationmentioning

confidence: 99%

“…at a concentration of 5.0 mg/kg body weight in a total volume of 1 mL/kg body weight. This dose was previously determined to effectively antagonize excitotoxic damage of cholinergic projection neurons in the MBN (Harkany et al, 1999b;Stuiver et al, 1996). MK-801 was applied acutely 1 h prior to Ab (1±42) infusion into the MBN based on previous experience (Stuiver et al, 1996;Harkany et al, 1999b).…”

Section: Animals Acute Lesion Procedures and Mk-801 Administrationmentioning

confidence: 99%

“…To monitor cellular consequences of Ab toxicity, Ab (1±42) and Ab (25±35) were applied to cholinergic projection neurons of the rat magnocellular nucleus basalis (MBN) as a neuronal model structure that allows correlative behavioural and neuroanatomical evaluation of neuronal injury. It is to be emphasized that Ab-induced lesions of the rat MBN mimic acute neuronal injury (Harkany et al, 1999a;Stuiver et al, 1996) and thereby model initial steps of neurotoxic signalling that may turn to pathological dimensions in AD. Moreover, the age-dependent involvement of NMDA receptors in Ab toxicity and the potential therapeutic role of their neuropharmacological modulation are discussed.…”

Section: Introductionmentioning

confidence: 99%

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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

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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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Section: Animals Acute Lesion Procedures and Mk-801 Administrationmentioning

confidence: 99%

Section: Animals Acute Lesion Procedures and Mk-801 Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

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261

151

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“…Most studies on the role of excessive Ca 2ϩ influx in cell death have focused on Ca 2ϩ entry via ligand-gated channels (Rothman and Olney, 1987;Choi, 1988); however, it is becoming increasingly recognized that VGCCs, particularly of the L-type, can be a route for toxic levels of Ca 2ϩ influx after a number of insults (Scriabine et al, 1989;Uematsu et al, 1989;Lobner and Lipton, 1993;Lipton, 1994;Stuiver et al, 1996). Furthermore, VGCCs represent a major Ca 2ϩ entry pathway even during the physiological activation of ligand-gated Ca 2ϩ channels (Miyakawa et al, 1992;Jaffe et al, 1994;Regehr and Tank, 1994;Stuart and Sakmann, 1994;Magee and Johnston, 1995;Yuste and Denk, 1995).…”

Section: Abstract: Hippocampal Neurons; Calcium Currents; Cell Deathmentioning

confidence: 99%

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

et al. 1997

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The expression of voltage-gated calcium (Ca 2ϩ ) channel activity in brain cells is known to be important for several aspects of neuronal development. In addition, excessive Ca 2ϩ influx has been linked clearly to neurotoxicity both in vivo and in vitro; however, the temporal relationship between the development of Ca 2ϩ channel activity and neuronal survival is not understood. Over a period spanning 28 d in vitro, progressive increases in high voltage-activated whole-cell Ca 2ϩ current and L-type Ca 2ϩ channel activity were observed in cultured hippocampal neurons. On the basis of single-channel analyses, these increases seem to arise in part from a greater density of functionally available L-type Ca 2ϩ channels. An increase in mRNA for the ␣ 1 subunit of L-type Ca 2ϩ channels occurred over a similar time course, which suggests that a change in gene expression may underlie the increased channel density. Parallel studies showed that hippocampal neuronal survival over 28 d was inversely related to increasing Ca 2ϩ current density. Chronic treatment of hippocampal neurons with the L-type Ca 2ϩ channel antagonist nimodipine significantly enhanced survival. Together, these results suggest that age-dependent increases in the density of Ca 2ϩ channels might contribute significantly to declining viability of hippocampal neurons. The results also are analogous to patterns seen in neurons of aged animals and therefore raise the possibility that long-term primary neuronal culture could serve as a model for some aspects of aging changes in hippocampal Ca 2ϩ channel function.

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“…automatic image analysis system (IBAS ) as described in detail in a Surgeries previous report (62 ). Briefly, in each experimental animal four sections of the parietal cortex with intervals of 200 mm were measured and the All surgeries were carried out under deep anaesthesia with sodium values averaged.…”

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confidence: 99%

Effect of Corticosterone and Adrenalectomy on NMDA‐Induced Cholinergic Cell Death in Rat Magnocellular Nucleus Basalis

Ábrahám

Veenema

Nyakas

et al. 1997

J Neuroendocrinology

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Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Abraham, N. V., Veenema, AH., Nyakas, C., Harkany, T., Bohus, BGJ., Luiten, PGM., & Ábrahám, I. (1997). Effect of corticosterone and adrenalectomy on NMDA-induced cholinergic cell death in rat magnocellular nucleus basalis. Journal of Neuroendocrinology, 9(9), 713-720. 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. Download date: 22-03-2019Journal of Neuroendocrinology, 1997, Vol. 9, 713-720 Effect of Key words: corticosterone, adrenalectomy, magnocellular nucleus basalis, cortex, astrocytes, neuroprotection. AbstractThe present study demonstrates the effects of adrenalectomy and subcutaneously administered corticosterone on N-methyl-d-aspartateinduced neurodegeneration in the cholinergic magnocellular basal nucleus of the rat. NMDA was unilaterally injected into the nucleus basalis at different plasma cor ticosterone concentrations in adrenalectomized rats, in adrenalectomized animals with subcutaneously implanted cholesterol-corticosterone pellets containing 25% or 100% corticosterone, and in sham-adrenalectomized controls. The neurotoxic impact of the NMDA injection in the various experimental groups was assessed by the loss of cholinergic fibers stained with acetylcholinesterase histochemistry in the parietal neocortex. Reactive cortical astrocytes as a result of the treatments were detected by glial fibrillary acidic protein immunohistochemistr y. Measurements of the densities of astrocytes and cholinergic fibers at the injected side of the brain were carried out by image analysis. Adrenalectomy significantly potentiated the NMDA-induced neurodegeneration by 50%, while chronic administration of corticosterone significantly attenuated the NMDA-neurotoxicity in a dose-dependent manner. Compared to the ADX group, 25% cor ticosterone application reduced the NMDA damage by 37%, whereas the 100% corticosterone pellet dimished NMDA neurotoxicity by 75%. Both ADX and ADX+corticosterone implantation enhanced the NMDA-induced GFAP immunoreactivity. The increase of GFAP immunoreactivity was most pronounced in the adrenalectomized rats supplied with the 100% corticosterone pellets.The results demonstrate that corticosterone exerts a potent neuroprotective effect on NMDA-induced neurotoxicity in the magnocellular nucleus basalis. The activated astroglia suggest that astrocytes may contribute to the benefical effec...

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In Vivo Protection against NMDA-induced Neurodegeneration by MK-801 and Nimodipine: Combined Therapy and Temporal Course of Protection

Cited by 55 publications

References 39 publications

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

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

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

Effect of Corticosterone and Adrenalectomy on NMDA‐Induced Cholinergic Cell Death in Rat Magnocellular Nucleus Basalis

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