Social Interaction Rescues Memory Deficit in an Animal Model of Alzheimer's Disease by Increasing BDNF-Dependent Hippocampal Neurogenesis

Hsiao, Ya Hsin; Hung, Hui Chi; Chen, Shun Hua; Gean, Po Wu

doi:10.1523/jneurosci.0747-14.2014

Cited by 120 publications

(92 citation statements)

References 48 publications

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“…2, the hippocampal and cortical BDNF expression in APP/PS1 mice were significantly less than that in WT control mice (n=5, p<0.01 vs. WT+Vehicle), consistent with previous findings. 28,39,40) In line with the behavioral data, chronic donepezil administration significantly enhanced the expression of hippocampal and cortical BDNF in APP/PS1 mice (n=5, p<0.01 vs. APP/PS1+Vehicle). Donepezil treatment did not affect the BDNF expression in WT control mice (n=5).…”

Section: Chronic Donepezil Administration Restores the Memory Impairmsupporting

confidence: 73%

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Wang

et al. 2017

Biological & Pharmaceutical Bulletin

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Alzheimer's disease (AD) is a most serious age-related neurodegenerative disorder accompanied with significant memory impairments in this world. Recently, microRNAs (miRNAs) have been reported to be invlolved in the pathophysiology of AD. Previous studies have shown that miRNA-206 (miR-206) is implicated in the pathogenesis of AD via suppressing the expression of brain-derived neurotrophic factor (BDNF) in the brain. Here, we examined the miR-206-3p and miR-206-5p expression in the hippocampus and cortex of Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice treated with donepezil, a drug approved for treating AD in clinic. We found that the expression of miR-206-3p was significantly up-regulated in the hippocampus and cortex of APP/PS1 mice, while donepezil administration significantly reversed this dysfunction. In addition, enhancing the miR-206-3p level by the usage of AgomiR-206-3p significantly attenuated the anti-dementia effects of donepezil in APP/PS1 mice. Together, these results suggested that miR-206-3p is involved in the anti-dementia effects of donepezil, and could be a novel pharmacological target for treating AD.Key words Alzheimer's disease; brain-derived neurotrophic factor; donepezil; microRNA (miRNA)-206-3pAlzheimer's disease (AD) is a serious neurodegenerative disorder in old people, and always accompanied with significant memory impairments, affecting mainly the hippocampus and frontal cortex. 1,2) AD patients display relatively slow, chronic but progressive neurodegeneration and memory impairments, ultimately leading to full dementia.3,4) Recent survey found that AD is responsible for about 50-60% of all cases of dementia in people over age 65. 3,4) The etiology of AD remains unclear, though many pathophysiologic hallmarks of this disease have been disclosed and are currently well established. They involve a complex network of interconnected factors such as cholinergic dysfunction, aggregation and accumulation of β-amyloid (Aβ), intracellular formation of neurofibrillary tangles composed by tau, oxidative stress, neuronal loss, and so on.5-8) A lot of reports have shown that brain-derived neurotrophic factor (BDNF) is critical for the establishment and maintenance of memory, while the dysfunction of BDNF system leads to memory impairments.9,10) It is known that BDNF combines to tyrosine kinase receptor B (TrkB) in the cell membrane, and then inducing the activation of several intracellular signaling pathways.11-13) Accumulating evidences have indicated that BDNF is implicated in the pathophysiology of AD. Previous studies have already found the reduced expression of BDNF in several brain regions (especially the hippocampus) of postmortem AD samples.14,15) By using the immunohistochemical method, Connor et al. found a significant reduction in not only intensity, but also the number of BDNF-immunoreactive cell in the hippocampus and cortex of AD samples.16) In addition, it was also thought that the Aβ-induced neurotoxicity and dendrite atrophy may due to a consequence of BDNF def...

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Section: Chronic Donepezil Administration Restores the Memory Impairmsupporting

confidence: 73%

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Wang

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Previous studies reported that 6-monthold APP/PS1 mice experience mild decline in social interaction function, exhibiting no preference to stay in the empty chamber versus the one having unfamiliar mouse Hsiao et al 2014). The present study revealed that 24-month-old APP/PS1 mice spent more time in the empty chamber than with the unfamiliar partner, indicating the occurrence of social interaction impairment.…”

Section: Discussionmentioning

confidence: 97%

“…Evidence has suggested that dysfunction of BDNF is a possible contributor to the pathology and symptoms of AD (Tapia-Arancibia et al 2008). BDNF is found to be decreased in APP/PS1 mice even in the early stages of AD-like pathology (Peng et al 2009;Hsiao et al 2014). Apart from BDNF, other neurotrophic factors, such as nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF), are also involved in normal aging and AD (Allen et al 2013;Budni et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/ PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

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“…Conversely, factors that protect the heart can also protect the brain and reduce the risk of developing AD and; physical activity is considered as the central of these factors [42][43][44]. In addition, it is well known that consuming a healthy heart diet is associated with reduction of AD and dementia [45][46][47][48].…”

Section: Resultsmentioning

confidence: 99%

Risk Factors in Induction and Progression of Alzheimer’s Disease: Impacton Protection and Disease-Modifying Factors

Ali¹

2017

Brain Disord Ther

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to memory loss and nerve cell death throughout the brain. It is the most common cause of dementia and represents the most important problem in elderly. Dementia characterized mainly by decline in memory, cognitive skills and ability to perform everyday activities as well as behavioral dysfunction. The decline occurs because neurons involved in cognitive function have been destroyed and affected other parts of the brain involved in different basic bodily functions.

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Social Interaction Rescues Memory Deficit in an Animal Model of Alzheimer's Disease by Increasing BDNF-Dependent Hippocampal Neurogenesis

Cited by 120 publications

References 48 publications

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Risk Factors in Induction and Progression of Alzheimer’s Disease: Impacton Protection and Disease-Modifying Factors

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