scholarly journals Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nanhui Yu ◽  
Yongpan Huang ◽  
Yu Jiang ◽  
Lianhong Zou ◽  
Xiehong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Tunel Staining ◽  
Ganoderma Lucidum Triterpenoids

Alzheimer’s disease (AD) is the most common cause of dementia among senior citizen. Ganoderma lucidum triterpenoids (GLTs) have nutritional health benefits and has been shown to promote health and longevity, but a protective effect of GLTs on AD damage has not yet been reported. The objective of this research was to elucidate the phylactic effect of GLTs on AD model mice and cells and to explore its underlying mechanisms. Morris water maze (MWM) test was conducted to detect changes in the cognitive function of mice. Hematoxylin-eosin (HE) staining was applied to observe pathological changes in the hippocampus. Silver nitrate staining was applied to observe the hippocampal neuronal tangles (NFTs). Apoptosis of the hippocampal neurons in mouse brain tissue was determined by TUNEL staining. The expression levels of apoptosis-related protein Bcl2, Bax, and caspase 3/cleaved caspase 3; antioxidative protein Nrf2, NQO1, and HO1; and ROCK signaling pathway-associated proteins ROCK2 and ROCK1 were measured by western blot. In vivo experiments show that 5-month-old APP/PS1 mice appeared to have impaired acquisition of spatial learning and GLTs could reduce cognitive impairment in AD mice. Compared to normal mice, the hippocampus of APP/PS1 mouse’s brains was severely damaged, while GLTs could alleviate this symptom by inhibiting apoptosis, relieving oxidative damage, and inactivating the ROCK signaling pathway. In in vitro cell experiments, Aβ25-35 was applied to induce hippocampal neurons into AD model cells. GLTs promoted cell proliferation, facilitated superoxide dismutase (SOD) expression, and inhibited malondialdehyde (MDA) and lactic dehydrogenase (LDH) expression of neurons. Our study highlights that GLTs improve cognitive impairment, alleviate neuronal damage, and inhibit apoptosis in the hippocampus tissues and cells in AD through inhibiting the ROCK signaling pathway.

scholarly journals Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats withAβ1–40-Induced Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hai-yan Hu ◽  
Zhi-hui Cui ◽  
Hui-qin Li ◽  
Yi-ru Wang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Ming Dynasty ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Apoptotic Signaling ◽  
Chinese Herbal

Alzheimer’s disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in theComplete Works of Jingyueduring the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects inAβ1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection ofAβ1–40into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with theAβ1–40-injected group (P<0.05orP<0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P<0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect againstAβ1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

scholarly journals Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1–42 synaptotoxicity

2017 ◽  
Vol 216 (10) ◽  
pp. 3161-3178 ◽  
Author(s):  
Xiaoyi Qu ◽  
Feng Ning Yuan ◽  
Carlo Corona ◽  
Silvia Pasini ◽  
Maria Elena Pero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Dendritic Spines ◽  
Posttranslational Modifications ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Driving Factors ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation

Oligomeric Amyloid β1–42 (Aβ) plays a crucial synaptotoxic role in Alzheimer’s disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ. We explored the mechanism of rescue and found that stabilization of dynamic MTs promotes tau-dependent loss of dendritic spines and tau hyperphosphorylation. Collectively, these results uncover a novel role for mDia1 in Aβ-mediated synaptotoxicity and demonstrate that inhibition of MT dynamics and accumulation of PTMs are driving factors for the induction of tau-mediated neuronal damage.

scholarly journals Platycodon grandiflorum Root Protects against Aβ-Induced Cognitive Dysfunction and Pathology in Female Models of Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 207
Author(s):  
Yunkwon Nam ◽  
Soo Jung Shin ◽  
Yong Ho Park ◽  
Min-Jeong Kim ◽  
Seong Gak Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Hippocampal Formation ◽  
Histopathological Analysis ◽  
Root Extract ◽  
Platycodon Grandiflorum ◽  
5Xfad Mice

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by irreversible cognitive dysfunction. Amyloid beta (Aβ) peptide is an important pathological factor that triggers the progression of AD through accumulation and aggregation, which leads to AD-related pathologies that consequently affect cognitive functions. Interestingly, several studies have reported that Platycodon grandiflorum root extract (PGE), besides exhibiting other bioactive effects, displays neuroprotective, anti-neuroinflammatory, and cognitive-enhancing effects. However, to date, it is not clear whether PGE can affect AD-related cognitive dysfunction and pathogenesis. Therefore, to investigate whether PGE influences cognitive impairment in an animal model of AD, we conducted a Y-maze test using a 5XFAD mouse model. Oral administration of PGE for 3 weeks at a daily dose of 100 mg/kg significantly ameliorated cognitive impairment in 5XFAD mice. Moreover, to elucidate the neurohistological mechanisms underlying the PGE-mediated alleviative effect on cognitive dysfunction, we performed histological analysis of hippocampal formation in these mice. Histopathological analysis showed that PGE significantly alleviated AD-related pathologies such as Aβ accumulation, neurodegeneration, oxidative stress, and neuroinflammation. In addition, we observed a neuroprotective and antioxidant effect of PGE in mouse hippocampal neurons. Our findings suggest that administration of PGE might act as one of the therapeutic agents for AD by decreasing Aβ related pathology and ameliorating Aβ induced cognitive impairment.

Rosuvastatin Calcium Affects Alzheimer's Disease Through Regulating Defensive Transduction Pathways of Oxidative and Chemical Stress Signaling Pathway

2019 ◽  
Vol 9 (10) ◽  
pp. 1414-1419
Author(s):  
Zhongjin Liu ◽  
Ruiqing Li ◽  
Chunmei Zhang ◽  
Jia Liu ◽  
Haiyan Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Ability ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Sham Operation ◽  
Sod Activity ◽  
Sham Operation Group ◽  
Operation Group ◽  
Rosuvastatin Calcium

Alzheimer's disease (AD) treatment is not effective. Statins are lipid-lowering drugs. However, the role and mechanism of statins for treating AD remains unclear. SD rats were separated into sham operation group; AD group and rosuvastatin calcium group followed by analysis of cognitive function and neuronal morphology. ELISA was to measure the level of TNF-α and IL-1; SOD activity and ROS levels were measured,. Real-time quantitative PCR was to analyze Bcl-2 and Bax level. The expression of Nuclear Erythroid 2-Related Factor 2/Antioxidant Responsive Element (NRF2/ARE) signaling pathway was analyzed by Western blot. Compared with sham operation group, the cognitive ability of the AD group was significantly decreased; with elevated secretion of TNF-α and IL-1, decreased SOD activity, increased ROS generation, decreased Bcl-2 expression as well as increased Bax expression (P < 0.05). In addition, AD group rats showed neuronal damage in the hippocampus and decreased expression of NRF2 and ARE. However, rosuvastatin calcium treatment improved cognitive ability, decreased TNF-α and IL-1 secretion, increased SOD activity, decreased ROS content, increased Bcl-2 expression and decreased Bax expression as well as ameliorated neuronal damage, increased number of nerve cells, and increased expression of NRF2 and ARE. Rosuvastatin calcium can inhibit the oxidative stress and inflammation, inhibit the apoptosis of hippocampus cells and improve the cognitive ability of AD rats by regulating NRF2/ARE signaling pathway.

scholarly journals miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Zheng ◽  
Fan Hu ◽  
Yang Zhou ◽  
Juan Zhang ◽  
Jie Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Hippocampal Neurons ◽  
Therapeutic Strategy ◽  
Memory Deficits ◽  
Synaptic Activity ◽  
Memory Impairments ◽  
Model Of Alzheimer’S Disease

AbstractAberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer’s disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD.

scholarly journals Clinical and Biophysical Principles of Vascular Dementia and Alzheimer’s Disease Treatment

2019 ◽  
Vol 5 (5) ◽  
pp. 57-72 ◽  
Author(s):  
S. Bulgakova ◽  
P. Romanchuk ◽  
A. Volobuev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Hippocampal Neurons ◽  
Structural Changes ◽  
Neuronal Damage ◽  
Oxidant Stress ◽  
Cerebral Hypoperfusion ◽  
Term Care ◽  
Β Amyloid

Biophysics of blood circulation in Alzheimer’s disease is characterized by disorders of laminar blood flow and cerebral hypoperfusion. As a result, failure intracellular metabolism, there is a cascade of changes in neurons associated with the processes of excitotoxicity and oxidant stress, which in turn stimulates amyloidogenesis. Experimental and 25-year observations have shown that the long-existing state of hypoperfusion leads to hippocampal disorders. This process is accompanied by memory impairment, structural changes in the capillaries in the hippocampus, impaired glucose and protein metabolism, β–amyloid deposition, activation of glial tissue, death of hippocampal neurons. Neuroreflex disruption in the ‘cerebral heart’ and a violation of cerebrovascular homeostasis contributes to the development of vascular dementia through the following mechanisms, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neuronal damage, the increase in β–amyloid neurotoxicity, apoptosis, etc. The duration of therapy with antiglutamatergic and multimodal drugs in Alzheimer’s disease requires constant multidisciplinary monitoring of targets and medical and social control in the system of long-term care. Lifelong acquisition of knowledge, information positive Nano communication enable the preservation of mental health and active longevity. Innovative methods of P4-medicine of neuroplasticity management allow to carry out timely prevention of the factors reducing neuroplasticity, to keep factors of positive influence on visceral and cognitive brain, and the main thing — in due time to apply in practical health care the combined methods of preservation and development of the human cognitive brain.

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