Role of Kalirin and mouse strain in retention of spatial memory training in an Alzheimer’s disease model mouse line

Russo-Savage, Lillian; Rao, Vishwanatha K.S.; Eipper, Betty A.; Mains, Richard E.

doi:10.1016/j.neurobiolaging.2020.07.006

Cited by 11 publications

(7 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, no study has reported a significantly greater amount in Aβ levels in male 3xTg-AD mice compared to females. Recently, Russo-Savage et al measured greater levels of human APP in the somatosensory cortex of females at 3 months old using western blot [ 74 ]. However, this was only evaluated between a single mouse from each sex and no analysis was performed on AβPP processing enzymes or Aβ production.…”

Section: Sexual Dimorphism In the Clinical Presentation Of Alzheimer’s Disease Patientsmentioning

confidence: 99%

Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research

Dennison

Ricciardi

Lohse

et al. 2021

JAD

View full text Add to dashboard Cite

Female sex is a leading risk factor for developing Alzheimer’s disease (AD). Sexual dimorphism in AD is gaining attention as clinical data show that women are not only more likely to develop AD but also to experience worse pathology and faster cognitive decline. Pre-clinical AD research in animal models often neglects to address sexual dimorphism in evaluation of behavioral or molecular characteristics and outcomes. This can compromise its translation to a clinical setting. The triple-transgenic AD mouse model (3xTg-AD) is a commonly used but unique AD model because it exhibits both amyloid and tau pathology, essential features of the human AD phenotype. Mounting evidence has revealed important sexually dimorphic characteristics of this animal model that have yet to be reviewed and thus, are often overlooked in studies using the 3xTg-AD model. In this review we conduct a thorough analysis of reports of sexual dimorphism in the 3xTg-AD model including findings of molecular, behavioral, and longevity-related sex differences in original research articles through August 2020. Importantly, we find results to be inconsistent, and that strain source and differing methodologies are major contributors to lack of consensus regarding traits of each sex. We first touch on the nature of sexual dimorphism in clinical AD, followed by a brief summary of sexual dimorphism in other major AD murine models before discussing the 3xTg-AD model in depth. We conclude by offering four suggestions to help unify pre-clinical mouse model AD research inspired by the NIH expectations for considering sex as a biological variable.

show abstract

Section: Sexual Dimorphism In the Clinical Presentation Of Alzheimer’s Disease Patientsmentioning

confidence: 99%

Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research

Dennison

Ricciardi

Lohse

et al. 2021

JAD

View full text Add to dashboard Cite

show abstract

“…Although the MWM test has been widely used to evaluate CUMS-induced deficits in spatial learning and memory [ 35 , 36 , 37 , 38 ], swimming in the MWM may be a stressor to animals and affect the CUMS-mediated results. The Barnes maze test (BMT) is generally thought to be less stressful than the Morris water maze test according to plasma corticosterone levels and more sensitive to early cognitive deficits [ 39 , 40 ]. To determine whether the swimming in the MWM affects the results of the MWM test, another cohort of rats of both sexes received the same CUMS exposure and the BMT was performed to verify the results of the MWM test.…”

Section: Resultsmentioning

confidence: 99%

“…The BMT was used to evaluate spatial learning and memory. This test is generally thought to be less stressful than the Morris water maze test according to plasma corticosterone levels and more sensitive to early cognitive deficits [ 39 , 40 ]. The BMT consisted of three phases: (1) habituation, (2) training, and (3) testing.…”

Section: Methodsmentioning

confidence: 99%

Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience in Rats

Tan

Guan

et al. 2023

IJMS

View full text Add to dashboard Cite

Klotho (KL) is a glycosyl hydrolase and aging-suppressor gene. Stress is a risk factor for depression and anxiety, which are highly comorbid with each other. The aim of this study is to determine whether KL is regulated by estrogen and plays an important role in sex differences in stress resilience. Our results showed that KL is regulated by estrogen in rat hippocampal neurons in vivo and in vitro and is essential for the estrogen-mediated increase in the number of presynaptic vesicular glutamate transporter 1 (Vglut1)-positive clusters on the dendrites of hippocampal neurons. The role of KL in sex differences in stress response was examined in rats using 3-week chronic unpredictable mild stress (CUMS). CUMS produced a deficit in spatial learning and memory, anhedonic-like behaviors, and anxiety-like behaviors in male but not female rats, which was accompanied by a reduction in KL protein levels in the hippocampus of male but not female rats. This demonstrated the resilience of female rats to CUMS. Interestingly, the knockdown of KL protein levels in the rat hippocampus of both sexes caused a decrease in stress resilience in both sexes, especially in female rats. These results suggest that the regulation of KL by estrogen plays an important role in estrogen-mediated synapse formation and that KL plays a critical role in the sex differences in cognitive deficit, anhedonic-like behaviors, and anxiety-like behaviors induced by chronic stress in rats, highlighting an important role of KL in sex differences in stress resilience.

show abstract

“…Although the MWM has been widely used to evaluate CUMS-induced deficit in spatial learning and memory [35][36][37][38], swimming in the MWM which may be a stressor to animals and affect the CUMS-mediated results. The Barnes maze test (BMT) is generally thought to be less stressful than the Morris water maze according to plasma corticosterone levels, and more sensitive to early cognitive deficits [39,40]. To determine whether the swimming in the MWM test affects the results of the MWM, another cohort of rats of both sexes receiving the same CUMS exposure, the BMT was used to verify the results of the MWM test.…”

Section: Cums-induced Deficit In Spatial Learning and Memory Anhedoni...mentioning

confidence: 99%

Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience

Tan¹,

Li²,

Guan³

et al. 2022

Preprint

View full text Add to dashboard Cite

Klotho (KL) is a glycosyl hydrolase and aging-suppressor gene. Stress is a risk factor for depression and anxiety that are highly comorbid with each other. The aim of this study was to determine KL is regulated by estrogen and plays an important role in sex differences in stress resilience. Our results showed that KL was regulated by estrogen in rat hippocampal neurons in vivo and in vitro and was essential for estrogen-mediated increase in the number of presynaptic vesicular glutamate transporter 1 (Vglut1) positive clusters on the dendrites of hippocampal neurons. The role of KL in sex differences in stress responses was examined in rats using three-week chronic unpredictable mild stress (CUMS). CUMS produced a deficit in spatial learning and memory, anhedonic-like and anxiety-like behaviors in male but not female rats, which was accompanied by a reduction in KL protein levels in the hippocampus of male, but not female rats. This demonstrated the resilience of female rats to CUMS. Interestingly, knockdown of KL protein levels in the rat hippocampus of both sexes caused a decrease in stress resilience in both sexes, especially in female rats. These results suggest that regulation of KL by estrogen plays an important role in estrogen-mediated synapse formation, and KL plays a critical role in the sex differences in cognitive deficit, anhedonic-like and anxiety-like behaviors induced by chronic stress in rats, highlighting an important role of KL in sex differences in stress resilience.

show abstract

Role of Kalirin and mouse strain in retention of spatial memory training in an Alzheimer’s disease model mouse line

Cited by 11 publications

References 84 publications

Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research

Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research

Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience in Rats

Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience

Contact Info

Product

Resources

About