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Impairment in recall after contextual fear conditioning and activity dependent protein translation in ovariectomized Alzheimer’s disease mouse model
Author(s) -
Kommaddi Reddy Peera,
Diwakar Latha,
Gowaikar Ruturaj,
Karunakaran Smitha,
Ravindranath Vijayalakshmi
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041328
Subject(s) - ovariectomized rat , recall , estrogen , hippocampus , disease , endocrinology , medicine , neuroprotection , psychology , physiology , cognitive psychology
Background Female sex is one of the major risk factor for developing late‐onset Alzheimer’s disease (AD). Human studies have demonstrated that the prevalence of AD is higher in women compared with men. Although neuroprotective effect of estrogen is well recognized, the underlying pathogenic mechanisms explaining the higher burden of AD in women are unclear, taking into account the longer lifespan in women. Thus, we attempted to investigate the gender‐specific differences during the progression of the disease in an AD mouse model. We examined behavioural and activity dependent protein translation in female AD mice after ovariectomy and compared it with sham‐operated female mice of similar age in order to study the effect of female sex hormones in female AD mouse. Methods Wild type and APP/PS1 female mice underwent an ovariectomy and sham surgery. The cognitive task we used in AD mouse model is the recall following contextual fear‐conditioning (cFC). After ovariectomy and behavioural assessment we prepared synaptoneurosomes from hippocampus and performed 35 S methionine incorporation assay without or with KCl stimulation. Results Female APP/PS1 mice did not show deficient recall upon cFC at 2, 4 and 6 months of age. However, female APP/PS1 mice showed deficient recall following cFC only after 8 months of age and this was sustained as mice aged further. Activity dependent synaptic protein translation was affected only at 8 months of age and no deficits were observed in 4 months old APP/PS1 female mice. In contrast, ovariectomized APP/PS1 mice displayed deficient recall upon cFC at 4 months of age and this recall deficits were sustained until 8 months of age as examined. Further, activity dependent protein translation was also impaired in 4 months old ovariectomized APP/PS1 mice compared with sham female APP/PS1 mice and this impairment was persistent until 8 months of age in these ovariectomized APP/PS1 mice. Conclusions Our results indicate that deficits in recall following cFC and loss of activity dependent protein translation occurred in female APP/PS1 mice only as they aged or if they were ovariectomized at younger age. Thus, estrogen plays a protective role even in the presence of relatively higher levels of β‐amyloid.