β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease

• DOI: 10.1523/jneurosci.21-12-04125.2001
• Publication Date: 2018-04-05T02:15:54Z
• Authors: Kelly T. Dineley; Marcus Westerman; Duy Bui; Karen Bell; Karen Hsiao Ashe; J. David Sweatt
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

Alzheimer's Disease (AD) is the most common of senile dementias, prevalence which increasing rapidly, with a projected 14 million affected worldwide by 2025. The signal transduction mechanisms that underlie learning and memory derangements in AD are poorly understood. β-Amyloid (Aβ) peptides elevated brain tissue patients principal component amyloid plaques, major criterion for postmortem diagnosis disease. Using acute organotypic hippocampal slice preparations, we demonstrate Aβ peptide 1-42 (Aβ42) couples to mitogen-activated protein kinase (MAPK) cascade via α7 nicotinic acetylcholine receptors (nAChRs). In vivo elevation Aβ, such as exhibited an animal model AD, leads upregulation nAChR protein. occurs concomitantly downregulation 42 kDa isoform extracellular signal-regulated (ERK2) MAPK hippocampi aged animals. phosphorylation state transcriptional mediator long-term potentiation downstream target ERK cascade, cAMP-regulatory element binding (CREB) protein, were also. These findings support derangement hippocampus cascades arises consequence increased burden chronic activation nAChR-dependent manner eventually ERK2 decreased CREB