title: Early effects of Aβ1-42 oligomers injection in mice: Involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways.
abstract: Neuronal and synaptic loss are the best pathological correlates for memory decline in Alzheimer's disease (AD). Soluble beta-amyloid oligomers (AβO) are considered to putatively play a crucial role in the early synapse loss and cognitive impairment observed in AD. Evidence suggests that oxidative stress and apoptosis are involved in the mechanism of Aβ-induced neurotoxicity and AD pathogenesis. This study aimed to explore the molecular mechanisms that contribute to the early memory deficits induced by intracerebroventricular injection of AβO in mice. Ten days after a single AβO injection memory impairments were observed, as measured by Morris water maze and novel object recognition tests. Cognitive decline was associated with increased oxidative stress, caspase-9 activation, and decreased hippocampal synaptophysin immunoreactivity. Furthermore, GSH levels were significantly higher in AβO-injected mice than in sham mice, showing that a protective mechanism might develop due to oxidative stress. Additionally, AβO-induced toxicity was aligned with an increment of the activation of Akt and ERK1/2, and reduced activity of GSK3. These findings suggest that AβO injection triggers a cascade of events that mimic the key neuropathological hallmarks of AD. Aβ acute injection helps to better understand how this peptide impairs specific signaling pathways leading to synaptic and memory dysfunctions. Thus, this model is a valid tool for investigating AD and may suggest a new way to develop neuroprotective therapies at such early stages of the disease.
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: fabiana.morroni@unibo.it.
authors: Fabiana
authors: F
authors: Morroni
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors: Giulia
authors: G
authors: Sita
authors: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto, 237, 47900 Rimini, Italy.
authors: Andrea
authors: A
authors: Tarozzi
authors: Department of Medical and Clinical Sciences, Alma Mater Studiorum-University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors: Roberto
authors: R
authors: Rimondini
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors: Patrizia
authors: P
authors: Hrelia
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Akt; Beta-amyloid; Cognitive impairment; ERK1/2; GSK3; Oxidative stress