Abstract
Alzheimer's disease (AD) is characterized by senile plaques (SP) of extracellular amyloid β peptides(Aβ), neurofibrillary tangles (NFT) of intracellular hyper-phosphorylated tau and widespread loss of neurons. Apoptosis is the main reason of neuronal loss. It is proved that Aβ triggers apoptotic cell death via the activation of caspase-dependent and - independent cell death effectors, respectively. Valproic acid (VPA) is a widely used mood stabilizer and antiepileptic drug. Our previous study showed that VPA treatment significantly reduced SP formation and improved memory deficits in transgenic AD model mice. The present study intended to explore the protective effect of VPA on neuronal loss in transgenic AD model mice and the possible mechanisms involved. Histological and ultra-structural analysis showed that VPA partially decreased the swollen mitochondria and neurophil and promoted neurite outgrowth in AD mice model. Meanwhile, VPA greatly rescued the neuronal loss in the brain of AD mice. TUNEL staining showed that VPA significantly reduced the number of apoptotic cells. Western blot analysis revealed that VPA notably down-regulated the expression of Caspase-3, Caspase-9 and Caspase-12, reduced the level of cytochrome C and Bax. The expression of the antiapoptotic protein Bcl-2 was increased after VPA treatment. Flow cytometry revealed that VPA significantly decreased intracellular level of Ca2+ and elevated mitochondrial membrane potential. Altogether, these results indicate that VPA protected AD mice via suppression of upstream factors of apoptosis, namely inhibition of both mitochondrial and endoplasmic reticulum pathway of apoptosis.
Keywords: Valproic acid, GSK-3β, apoptosis, Alzheimer’s disease
Current Alzheimer Research
Title:Valproic Acid Attenuates Neuronal Loss in the Brain of APP/PS1 Double Transgenic Alzheimer’s Disease Mice Model
Volume: 10 Issue: 3
Author(s): Zhimin Long, Min Zheng, Lei Zhao, Peng Xie, Cong Song, Yalan Chu, Weihong Song and Guiqiong He
Affiliation:
Keywords: Valproic acid, GSK-3β, apoptosis, Alzheimer’s disease
Abstract: Alzheimer's disease (AD) is characterized by senile plaques (SP) of extracellular amyloid β peptides(Aβ), neurofibrillary tangles (NFT) of intracellular hyper-phosphorylated tau and widespread loss of neurons. Apoptosis is the main reason of neuronal loss. It is proved that Aβ triggers apoptotic cell death via the activation of caspase-dependent and - independent cell death effectors, respectively. Valproic acid (VPA) is a widely used mood stabilizer and antiepileptic drug. Our previous study showed that VPA treatment significantly reduced SP formation and improved memory deficits in transgenic AD model mice. The present study intended to explore the protective effect of VPA on neuronal loss in transgenic AD model mice and the possible mechanisms involved. Histological and ultra-structural analysis showed that VPA partially decreased the swollen mitochondria and neurophil and promoted neurite outgrowth in AD mice model. Meanwhile, VPA greatly rescued the neuronal loss in the brain of AD mice. TUNEL staining showed that VPA significantly reduced the number of apoptotic cells. Western blot analysis revealed that VPA notably down-regulated the expression of Caspase-3, Caspase-9 and Caspase-12, reduced the level of cytochrome C and Bax. The expression of the antiapoptotic protein Bcl-2 was increased after VPA treatment. Flow cytometry revealed that VPA significantly decreased intracellular level of Ca2+ and elevated mitochondrial membrane potential. Altogether, these results indicate that VPA protected AD mice via suppression of upstream factors of apoptosis, namely inhibition of both mitochondrial and endoplasmic reticulum pathway of apoptosis.
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Cite this article as:
Long Zhimin, Zheng Min, Zhao Lei, Xie Peng, Song Cong, Chu Yalan, Song Weihong and He Guiqiong, Valproic Acid Attenuates Neuronal Loss in the Brain of APP/PS1 Double Transgenic Alzheimer’s Disease Mice Model, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030005
DOI https://dx.doi.org/10.2174/1567205011310030005 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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