Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice
Abstract Background The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-023-00545-4 |
| _version_ | 1797578557006807040 |
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| author | Raquel Jiménez-Herrera Ana Contreras Souhail Djebari Jaime Mulero-Franco Guillermo Iborra-Lázaro Danko Jeremic Juan Navarro-López Lydia Jiménez-Díaz |
| author_facet | Raquel Jiménez-Herrera Ana Contreras Souhail Djebari Jaime Mulero-Franco Guillermo Iborra-Lázaro Danko Jeremic Juan Navarro-López Lydia Jiménez-Díaz |
| author_sort | Raquel Jiménez-Herrera |
| collection | DOAJ |
| description | Abstract Background The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ 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 Aβ 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 Aβ 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. Aβ 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. |
| first_indexed | 2024-03-10T22:23:32Z |
| format | Article |
| id | doaj.art-be5622c41db4463aadbe40677ff28fb6 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-03-10T22:23:32Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-be5622c41db4463aadbe40677ff28fb62023-11-19T12:11:20ZengBMCBiology of Sex Differences2042-64102023-09-0114111910.1186/s13293-023-00545-4Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male miceRaquel Jiménez-Herrera0Ana Contreras1Souhail Djebari2Jaime Mulero-Franco3Guillermo Iborra-Lázaro4Danko Jeremic5Juan Navarro-López6Lydia Jiménez-Díaz7Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaNeurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of Medicine of Ciudad Real, University of Castilla-La ManchaAbstract Background The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ 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 Aβ 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 Aβ 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. Aβ 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.https://doi.org/10.1186/s13293-023-00545-4Alzheimer’s diseaseAmyloid-βAβ 1–42Spatial memoryLTPHippocampus |
| spellingShingle | Raquel Jiménez-Herrera Ana Contreras Souhail Djebari Jaime Mulero-Franco Guillermo Iborra-Lázaro Danko Jeremic Juan Navarro-López Lydia Jiménez-Díaz Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice Biology of Sex Differences Alzheimer’s disease Amyloid-β Aβ 1–42 Spatial memory LTP Hippocampus |
| title | Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice |
| title_full | Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice |
| title_fullStr | Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice |
| title_full_unstemmed | Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice |
| title_short | Systematic characterization of a non-transgenic Aβ 1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice |
| title_sort | systematic characterization of a non transgenic aβ 1 42 amyloidosis model synaptic plasticity and memory deficits in female and male mice |
| topic | Alzheimer’s disease Amyloid-β Aβ 1–42 Spatial memory LTP Hippocampus |
| url | https://doi.org/10.1186/s13293-023-00545-4 |
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