Dataset Information

Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.

ABSTRACT: Estrogen has been known to reduce the development of Alzheimer's disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Aβ) degradation and affects Aβ-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERα) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Aβ (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of ERα knockout mice. In our present study, Aβ was accumulated more in the ERα knockout mice brain and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. These results suggest that estrogen may protect memory impairment by stimulating the degradation of Aβ and down-regulate neurogenic inflammation as well as amyloidogenesis.

SUBMITTER: Hwang CJ

PROVIDER: S-EPMC4510915 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.

Hwang Chul Ju CJ Yun Hyung-Mun HM Park Kyung-Ran KR Song Ju Kyung JK Seo Hyun Ok HO Hyun Byung Kook BK Choi Dong Young DY Yoo Hwan-Soo HS Oh Ki-Wan KW Hwang Dae Yeun DY Han Sang-Bae SB Hong Jin Tae JT

Molecular neurobiology 20140817 1

Estrogen has been known to reduce the development of Alzheimer's disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Aβ) degradation and affects Aβ-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERα) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Aβ (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance tes ...[more]

PMID: 25128029

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Project description:BackgroundAlzheimer's disease (AD) is characterized by memory decline and mood alterations. A growing body of evidence implicates stress and other social determinants of health as potential contributors to the progressive cerebral alterations that culminate in AD. In the current study, we investigated the impact of neonatal maternal separation (MS) on the susceptibility of male and female mice to AD-associated memory impairments and depressive-like behavior in adulthood, and on brain levels of pro-inflammatory cytokines and neurotransmitters.MethodologyMale and female Swiss mice were exposed to MS for 180 min daily from post-natal day 1 to 10. Seventy days post-MS, mice received an intracerebroventricular infusion of amyloid-β oligomers (AβOs), and memory and mood were evaluated. Levels of TNF-α, IL-1β, serotonin, dopamine, and related metabolites were determined in the cortex and hippocampus.ResultsPrevious exposure to MS alone did not cause memory impairments in adult mice. Interestingly, however, MS increased the susceptibility of adult male mice to memory impairment and depressive-like behavior induced by AβOs, and potentiated the inhibitory impact of AβOs on memory in adult females. Females were more susceptible to depressive-like behavior caused by a low dose of AβOs, regardless of MS. No changes in IL-1β were found. A decrease in TNF-α was selectively found in females exposed to MS that received an infusion of 1 pmol AβOs. MS led to an increase in serotonin (5-HT) in the hippocampus of male mice, without influencing the levels of the serotonin metabolite, 5-HIAA. Changes in serotonin turnover were predominantly observed in the cortex of female mice. No changes in dopamine or its metabolites were induced by MS or AβOs in male or female mice.ConclusionsNeonatal MS enhances the susceptibility of adult mice to AD-associated cognitive deficits and depressive-like behavior in a sex-specific manner. This suggests that early life stress may play a role in the development of AD.

Dataset Information

Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.

Publications

Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides.

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