PMID- 37716988
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20231121
IS  - 2042-6410 (Electronic)
IS  - 2042-6410 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Sep 16
TI  - Systematic characterization of a non-transgenic Abeta(1-42) amyloidosis model: 
      synaptic plasticity and memory deficits in female and male mice.
PG  - 59
LID - 10.1186/s13293-023-00545-4 [doi]
LID - 59
AB  - BACKGROUND: The amyloid-beta (Abeta) cascade is one of the most studied theories linked 
      to AD. In multiple models, Abeta 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 Abeta(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: Abeta(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. Abeta(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.
CI  - (c) 2023. Society for Women's Health Research and BioMed Central Ltd.
FAU - Jimenez-Herrera, Raquel
AU  - Jimenez-Herrera R
AUID- ORCID: 0000-0002-8755-0392
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Contreras, Ana
AU  - Contreras A
AUID- ORCID: 0000-0002-2185-0851
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Djebari, Souhail
AU  - Djebari S
AUID- ORCID: 0000-0002-8044-6461
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Mulero-Franco, Jaime
AU  - Mulero-Franco J
AUID- ORCID: 0009-0004-3304-8825
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Iborra-Lazaro, Guillermo
AU  - Iborra-Lazaro G
AUID- ORCID: 0000-0002-5122-4173
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Jeremic, Danko
AU  - Jeremic D
AUID- ORCID: 0000-0001-9495-972X
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain.
FAU - Navarro-Lopez, Juan
AU  - Navarro-Lopez J
AUID- ORCID: 0000-0002-1877-7833
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain. Juan.Navarro@uclm.es.
FAU - Jimenez-Diaz, Lydia
AU  - Jimenez-Diaz L
AUID- ORCID: 0000-0001-9121-0334
AD  - Neurophysiology and Behavior Lab, Biomedical Research Center (CRIB), School of 
      Medicine of Ciudad Real, University of Castilla-La Mancha, 13071, Ciudad Real, 
      Spain. Lydia.Jimenez@uclm.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230916
PL  - England
TA  - Biol Sex Differ
JT  - Biology of sex differences
JID - 101548963
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Female
MH  - Male
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Neuronal Plasticity
MH  - *Amyloidosis
MH  - *Alzheimer Disease
MH  - Mice, Transgenic
MH  - Memory Disorders
PMC - PMC10504764
OAB - This study focuses on investigating how amyloid-beta (Abeta), a key toxic protein in 
      Alzheimer's disease (AD), impacts memory and functioning of the synapses in both 
      male and female mice.Our primary objective was to comprehensively understand the 
      impact of Abeta(1-42), a specific form of Abeta, when introduced into the brain's 
      ventricles, focusing on memory processes associated with the hippocampus, a brain 
      region vital for learning and memory.Prior research established Abeta's significance 
      in AD and memory decline. However, despite the higher prevalence of AD in 
      females, the connection between Abeta, memory, and sex differences required further 
      exploration. Furthermore, findings from experiments utilizing Abeta transgenic mice 
      have offered conflicting outcomes. Here, by administering Abeta(1-42) to male and 
      female mice, we systematically assessed memory using cognitive tasks. Results 
      were consistent: memory deficits were evident in both sexes, persisting for up to 
      17 days post-injection.Delving deeper, we explored alterations in synaptic 
      plasticity, a cornerstone of learning and memory. Our investigations unveiled 
      disruptions in long-term potentiation (LTP) and long-term depression 
      (LTD)-essential synaptic processes-in both male and female mice subjected to 
      Abeta(1-42) injection.These intriguing findings underscore Abeta(1-42)'s lasting 
      influence on memory and synaptic function, emphasizing its role in early 
      AD-related cognitive decline. Additionally, our study highlights the potential of 
      this experimental model to investigate early AD across sex differences, offering 
      a promising alternative to the existing array Abeta transgenic mouse models and 
      addressing the need for a more consistent investigative framework.
OABL- eng
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid-beta
OT  - Abeta 1-42
OT  - Hippocampus
OT  - LTP
OT  - Sex differences
OT  - Spatial memory
COIS- The authors declare that they have no competing interests.
EDAT- 2023/09/17 00:41
MHDA- 2023/09/18 12:43
PMCR- 2023/09/16
CRDT- 2023/09/16 23:17
PHST- 2023/01/13 00:00 [received]
PHST- 2023/09/05 00:00 [accepted]
PHST- 2023/09/18 12:43 [medline]
PHST- 2023/09/17 00:41 [pubmed]
PHST- 2023/09/16 23:17 [entrez]
PHST- 2023/09/16 00:00 [pmc-release]
AID - 10.1186/s13293-023-00545-4 [pii]
AID - 545 [pii]
AID - 10.1186/s13293-023-00545-4 [doi]
PST - epublish
SO  - Biol Sex Differ. 2023 Sep 16;14(1):59. doi: 10.1186/s13293-023-00545-4.