No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study

E. von Linstow Roloff, Bettina Platt, Gernot Riedel

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Abstract

Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (betaA(1-40)) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semirandomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, betaA(1-40) was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. betaA(1-40) administered alone via intracerebroventricular (icv) minipumps (20 mug in 250 mul) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of betaA(1-40) in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracctam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intrahippocampal minipumps containing betaA(1-40) or reverse sequence betaA(40-1). This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (ip) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the betaA(1-40) group were amnesic. These data suggest that intrahippocampal betaA(1-40) administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals. (C) 2002 Elsevier Science Inc. All rights reserved.

Original languageEnglish
Pages (from-to)955-970
Number of pages15
JournalProgress in Neuro -Psychopharmacology & Biological Psychiatry
Volume26
Issue number5
DOIs
Publication statusPublished - 2002

Keywords

  • aluminium
  • Alzheimer's disease
  • beta-amyloid
  • memory
  • rats
  • water maze
  • LONG-TERM POTENTIATION
  • INDUCED NEUROFIBRILLARY DEGENERATION
  • FAMILIAL ALZHEIMERS-DISEASE
  • COGNITION-ENHANCING AGENT
  • SYNAPTIC PLASTICITY
  • PRECURSOR PROTEIN
  • LEARNING DEFICIT
  • TRANSGENIC MICE
  • ANIMAL-MODELS
  • INFUSED RATS

Cite this

@article{d23ed23ad29c4215ad79ca273d2199e7,
title = "No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study",
abstract = "Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (betaA(1-40)) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semirandomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, betaA(1-40) was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1{\%} sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. betaA(1-40) administered alone via intracerebroventricular (icv) minipumps (20 mug in 250 mul) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of betaA(1-40) in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracctam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intrahippocampal minipumps containing betaA(1-40) or reverse sequence betaA(40-1). This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (ip) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the betaA(1-40) group were amnesic. These data suggest that intrahippocampal betaA(1-40) administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals. (C) 2002 Elsevier Science Inc. All rights reserved.",
keywords = "aluminium, Alzheimer's disease, beta-amyloid, memory, rats, water maze, LONG-TERM POTENTIATION, INDUCED NEUROFIBRILLARY DEGENERATION, FAMILIAL ALZHEIMERS-DISEASE, COGNITION-ENHANCING AGENT, SYNAPTIC PLASTICITY, PRECURSOR PROTEIN, LEARNING DEFICIT, TRANSGENIC MICE, ANIMAL-MODELS, INFUSED RATS",
author = "{von Linstow Roloff}, E. and Bettina Platt and Gernot Riedel",
year = "2002",
doi = "10.1016/S0278-5846(02)00211-7",
language = "English",
volume = "26",
pages = "955--970",
journal = "Progress in Neuro -Psychopharmacology & Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",
number = "5",

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TY - JOUR

T1 - No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study

AU - von Linstow Roloff, E.

AU - Platt, Bettina

AU - Riedel, Gernot

PY - 2002

Y1 - 2002

N2 - Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (betaA(1-40)) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semirandomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, betaA(1-40) was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. betaA(1-40) administered alone via intracerebroventricular (icv) minipumps (20 mug in 250 mul) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of betaA(1-40) in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracctam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intrahippocampal minipumps containing betaA(1-40) or reverse sequence betaA(40-1). This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (ip) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the betaA(1-40) group were amnesic. These data suggest that intrahippocampal betaA(1-40) administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals. (C) 2002 Elsevier Science Inc. All rights reserved.

AB - Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (betaA(1-40)) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semirandomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, betaA(1-40) was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. betaA(1-40) administered alone via intracerebroventricular (icv) minipumps (20 mug in 250 mul) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of betaA(1-40) in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracctam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intrahippocampal minipumps containing betaA(1-40) or reverse sequence betaA(40-1). This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (ip) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the betaA(1-40) group were amnesic. These data suggest that intrahippocampal betaA(1-40) administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals. (C) 2002 Elsevier Science Inc. All rights reserved.

KW - aluminium

KW - Alzheimer's disease

KW - beta-amyloid

KW - memory

KW - rats

KW - water maze

KW - LONG-TERM POTENTIATION

KW - INDUCED NEUROFIBRILLARY DEGENERATION

KW - FAMILIAL ALZHEIMERS-DISEASE

KW - COGNITION-ENHANCING AGENT

KW - SYNAPTIC PLASTICITY

KW - PRECURSOR PROTEIN

KW - LEARNING DEFICIT

KW - TRANSGENIC MICE

KW - ANIMAL-MODELS

KW - INFUSED RATS

U2 - 10.1016/S0278-5846(02)00211-7

DO - 10.1016/S0278-5846(02)00211-7

M3 - Article

VL - 26

SP - 955

EP - 970

JO - Progress in Neuro -Psychopharmacology & Biological Psychiatry

JF - Progress in Neuro -Psychopharmacology & Biological Psychiatry

SN - 0278-5846

IS - 5

ER -