Abstract
Caffeoylquinic acid (CQA) is a natural polyphenol with evidence of antioxidant and neuroprotective effects and prevention of deficits in spatial learning and memory. We studied the cognitive-enhancing effect of 3,4,5-tricaffeoylquinic acid (TCQA) and explored its cellular and molecular mechanism in the senescence-accelerated mouse prone 8 (SAMP8) model of aging and Alzheimer’s disease as well as in human neural stem cells (hNSCs). Mice were fed with 5 mg/kg of TCQA for 30 days and were tested in the Morris water maze (MWM). Brain tissues were collected for immunohistochemical detection of bromodeoxyuridine (BrdU) to detect activated stem cells and newborn neurons. TCQA-treated SAMP8 exhibited significantly improved cognitive performance in MWM compared to water-treated SAMP8. TCQA-treated SAMP8 mice also had significantly higher numbers of BrdU+/glial fibrillary acidic protein (GFAP+) and BrdU+/Neuronal nuclei (NeuN+) cells in the dentate gyrus (DG) neurogenic niche compared with untreated SAMP8. In hNSCs, TCQA induced cell cycle arrest at G0/G1, actin cytoskeleton organization, chromatin remodeling, neuronal differentiation, and bone morphogenetic protein signaling. The neurogenesis promoting effect of TCQA in the DG of SAMP8 mice might explain the cognition-enhancing influence of TCQA observed in our study, and our hNSCs in aggregate suggest a therapeutic potential for TCQA in aging-associated diseases.
Highlights
Aging and associated neurodegenerative conditions are a serious social problem
We studied the cognitive‐enhancing effect of 3,4,5‐ tricaffeoylquinic acid (TCQA) and explored its cellular and molecular mechanism in the senescence‐accelerated mouse prone 8 (SAMP8) model of aging and Alzheimer’s disease as well as in human neural stem cells
The neurogenesis promoting effect of TCQA in the dentate gyrus (DG) of SAMP8 mice might explain the cognition‐enhancing influence of TCQA observed in our study, and our human neural stem cells (hNSCs) in aggregate suggest a therapeutic potential for TCQA in aging‐associated diseases
Summary
The United Nations report that the population aged > 60 years numbered 962 million in 2017 comprising 13% of the global population and is projected to be 2.1 billion in 2050. Amyloid beta (Aβ) aggregation forming senile plaques and accumulation of tau in neurofibrillary tangles characterize AD. These changes lead to neuronal and synaptic loss [2] as well as, excitotoxicity, oxidative stress and apoptosis [3]. Neuroinflammatory microglial activation is important in the development of AD pathology [4]. All these pathophysiological mechanisms of AD are crucial for choosing an appropriate animal model. A novel treatment approach of AD and other neurodegenerative diseases is to promote neuronal replacement in the affected tissue by stimulating neural stem cells (NSCs) and neural progenitor cells (NPCs) in the neurogenic niches
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