Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice
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Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice. / Christensen, Ditte Z; Thomsen, Morten Skøtt; Mikkelsen, Jens D.
In: Neurochemistry International, Vol. 63, No. 1, 07.2013, p. 54-60.Research output: Contribution to journal › Journal article › Research
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TY - JOUR
T1 - Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice
AU - Christensen, Ditte Z
AU - Thomsen, Morten Skøtt
AU - Mikkelsen, Jens D
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2013/7
Y1 - 2013/7
N2 - Activity-regulated cytoskeletal-associated protein (Arc) and c-Fos are immediate early gene (IEG) products induced by novelty in the hippocampus and involved in the consolidation of synaptic plasticity and long-term memory. We investigated whether induction of arc and c-fos after exposure to a novel open field environment was compromised in different neocortical areas and the hippocampal formation in APP/PS1ΔE9 transgenic mice characterized by pronounced accumulation and deposition of beta amyloid (Aβ). Notably, the basal level of Arc and c-fos mRNA in the neocortex was significantly lower in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels in APP/PS1ΔE9 as in the wild-type mice. In contrast, synaptophysin levels did not differ between mutant and wild type mice, suggesting that the observed effect was not due to a general decrease in the number of presynapses. These data suggest a reduction in basal and novelty-induced neuronal activity in a transgenic mouse model of Alzheimer's disease, which is most pronounced in cortical regions, indicating that a decreased functional response in IEG expression could be partly responsible for the cognitive deficits observed in patients with Alzheimer's disease.
AB - Activity-regulated cytoskeletal-associated protein (Arc) and c-Fos are immediate early gene (IEG) products induced by novelty in the hippocampus and involved in the consolidation of synaptic plasticity and long-term memory. We investigated whether induction of arc and c-fos after exposure to a novel open field environment was compromised in different neocortical areas and the hippocampal formation in APP/PS1ΔE9 transgenic mice characterized by pronounced accumulation and deposition of beta amyloid (Aβ). Notably, the basal level of Arc and c-fos mRNA in the neocortex was significantly lower in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels in APP/PS1ΔE9 as in the wild-type mice. In contrast, synaptophysin levels did not differ between mutant and wild type mice, suggesting that the observed effect was not due to a general decrease in the number of presynapses. These data suggest a reduction in basal and novelty-induced neuronal activity in a transgenic mouse model of Alzheimer's disease, which is most pronounced in cortical regions, indicating that a decreased functional response in IEG expression could be partly responsible for the cognitive deficits observed in patients with Alzheimer's disease.
KW - Amyloid beta-Protein Precursor
KW - Animals
KW - Biological Markers
KW - Cerebral Cortex
KW - Corticosterone
KW - Cytoskeletal Proteins
KW - Hippocampus
KW - Mice
KW - Mice, Transgenic
KW - Nerve Tissue Proteins
KW - Presenilin-1
KW - Proto-Oncogene Proteins c-fos
KW - RNA, Messenger
KW - Synapses
U2 - 10.1016/j.neuint.2013.04.002
DO - 10.1016/j.neuint.2013.04.002
M3 - Journal article
C2 - 23598246
VL - 63
SP - 54
EP - 60
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 1
ER -
ID: 111179343