title: 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.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Ditte Z
authors.initials: DZ
authors.lastname: Christensen
authors.forename: Morten S
authors.initials: MS
authors.lastname: Thomsen
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003598:Cytoskeletal Proteins / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D003345:Corticosterone