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.

Abstract

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.

• Authors: Ditte Z Christensen, Morten S Thomsen, Jens D Mikkelsen
• Journal: Neurochemistry international (Neurochem Int) Vol. 63 Issue 1 Pg. 54-60 (Jul 2013) ISSN: 1872-9754 [Electronic] England
• PMID: 23598246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Protein Precursor
• Biomarkers
• Cytoskeletal Proteins
• Nerve Tissue Proteins
• Presenilin-1
• Proto-Oncogene Proteins c-fos
• RNA, Messenger
• activity regulated cytoskeletal-associated protein
• Corticosterone

Topics

• Amyloid beta-Protein Precursor (genetics)
• Animals
• Biomarkers (metabolism)
• Cerebral Cortex (metabolism)
• Corticosterone (blood)
• Cytoskeletal Proteins (genetics)
• Hippocampus (metabolism)
• Mice
• Mice, Transgenic
• Nerve Tissue Proteins (genetics)
• Presenilin-1 (genetics)
• Proto-Oncogene Proteins c-fos (genetics)
• RNA, Messenger (metabolism)
• Synapses (metabolism)