Systematic characterization of a non-transgenic A[beta]1-42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice

• Published in: Biology of sex differences Vol. 14; no. 1
• Main Authors: Jiménez-Herrera, Raquel, Contreras, Ana, Djebari, Souhail, Mulero-Franco, Jaime, Iborra-Lázaro, Guillermo, Jeremic, Danko, Navarro-López, Juan, Jiménez-Díaz, Lydia
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 16.09.2023
• Subjects: Advertising executives; Alzheimer's disease; Amyloidosis; Comparative analysis; Genetic engineering; Spain
• ISSN: 2042-6410; 2042-6410
• DOI: 10.1186/s13293-023-00545-4

Background The amyloid-[beta] (A[beta]) cascade is one of the most studied theories linked to AD. In multiple models, A[beta] accumulation and dyshomeostasis have shown a key role in AD onset, leading to excitatory/inhibitory imbalance, the impairments of synaptic plasticity and oscillatory activity, and memory deficits. Despite the higher prevalence of Alzheimer's disease (AD) in women compared to men, the possible sex difference is scarcely explored and the information from amyloidosis transgenic mice models is contradictory. Thus, given the lack of data regarding the early stages of amyloidosis in female mice, the aim of this study was to systematically characterize the effect of an intracerebroventricular (icv.) injection of A[beta].sub.1-42 on hippocampal-dependent memory, and on associated activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse, in both male and female mice. Methods To do so, we evaluated long term potentiation (LTP) with ex vivo electrophysiological recordings as well as encoding and retrieval of spatial (working, short- and long-term) and exploratory habituation memories using Barnes maze and object location, or open field habituation tasks, respectively. Results A[beta].sub.1-42 administration impaired all forms of memory evaluated in this work, regardless of sex. This effect was displayed in a long-lasting manner (up to 17 days post-injection). LTP was inhibited at a postsynaptic level, both in males and females, and a long-term depression (LTD) was induced for the same prolonged period, which could underlie memory deficits. Conclusions In conclusion, our results provide further evidence on the shifting of LTP/LTD threshold due to a single icv. A[beta].sub.1-42 injection, which underly cognitive deficits in the early stages of AD. These long-lasting cognitive and functional alterations in males and females validate this model for the study of early amyloidosis in both sexes, thus offering a solid alternative to the inconsistence of amyloidosis transgenic mice models. Keywords: Alzheimer's disease, Amyloid-[beta], A[beta].sub.1-42, Spatial memory, LTP, Hippocampus, Sex differences