Preventive Effects of Continuous Betaine Intake on Cognitive Impairment and Aberrant Gene Expression in Hippocampus of 3xTg Mouse Model of Alzheimer’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Daisuke Ibi ◽  
Kazuki Hirashima ◽  
Yuya Kojima ◽  
Kahori Sumiya ◽  
Sari Kondo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Cognitive Impairment ◽  
Amyloid Β ◽  
Aberrant Expression ◽  
Synaptic Structure ◽  
Expression Of Genes ◽  
Model Of Alzheimer’S Disease

Background: The deposition of amyloid-β (Aβ) and hyperphosphorylation of tau are well-known as the pathophysiological features of Alzheimer’s disease (AD), leading to oxidative stress and synaptic deficits followed by cognitive symptoms. We already demonstrated that betaine (glycine betaine) prevented cognitive impairment and hippocampal oxidative stress in mice intracerebroventricularly injected with an active fragment of Aβ, whereas the effect of betaine in chronic models of AD remains unknown. Objective: Our objective was to investigate the effects of chronic betaine intake on cognitive impairment and aberrant expression of genes involved in synapse and antioxidant activity in the hippocampus of a genetic AD model. Methods: We performed cognitive tests and RT-PCR in the hippocampus in 3xTg mice, a genetic AD model. Results: Cognitive impairment in the Y-maze and novel object recognition tests became evident in 3xTg mice at 9 months old, and not earlier, indicating that cognitive impairment in 3xTg mice developed age-dependently. To examine the preventive effect of betaine on such cognitive impairment, 3xTg mice were fed betaine-containing water for 3 months from 6 to 9 months old, and subsequently subjected to behavioral tests, in which betaine intake prevented the development of cognitive impairment in 3xTg mice. Additionally, the expression levels of genes involved in synapse and antioxidant activity were downregulated in hippocampus of 3xTg mice at 9 months old compared with age-matched wild-type mice, which were suppressed by betaine intake. Conclusion: Betaine may be applicable as an agent preventing the progression of AD by improving the synaptic structure/function and/or antioxidant activity.

Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer’s Disease

2021 ◽  
pp. 1-20
Author(s):  
Daniel Cuervo-Zanatta ◽  
Jaime Garcia-Mena ◽  
Claudia Perez-Cruz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Cognitive Skills ◽  
Amyloid Β ◽  
Short Chain Fatty Acids ◽  
Mice Model ◽  
Model Of Alzheimer’S Disease ◽  
Cognitive Deficiencies

Background: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer’s disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-β pathology in male (M), but not in female (F) mice. Objective: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. Methods: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. Results: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. Conclusion: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD.

scholarly journals Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Pei-zhe Liang ◽  
Li Li ◽  
Ya-nan Zhang ◽  
Yan Shen ◽  
Li-li Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Control Group ◽  
Nissl Staining ◽  
Glymphatic System ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Background. Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer’s disease (AD). Amyloid-β (Aβ) is the key factor that triggers the course of AD, and reducing the deposition of Aβ in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aβ clearance. Objective. The purpose of this study was to explore whether EA modifies the accumulation of Aβ through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods. Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aβ accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results. This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aβ accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion. EA treatment might reduce Aβ accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

Berberine-Albumin Nanoparticles: Preparation, Thermodynamic Study and Evaluation Their Protective Effects Against Oxidative Stress in Primary Neuronal Cells as a Model of Alzheimer’s Disease

2021 ◽  
Vol 17 (6) ◽  
pp. 1088-1097
Author(s):  
Yaohui Zhang ◽  
Lixiang Wang ◽  
Guichen Li ◽  
Jianyuan Gao
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Molecular Docking ◽  
Morphological Changes ◽  
Neuronal Cultures ◽  
Protective Effects ◽  
Cellular Assays ◽  
Model Of Alzheimer’S Disease

Berberine has shown an outstanding antioxidant activity, however the low bioavailability limits its applications in pharmaceutical platforms. Therefore, in this paper, after fabrication of the berberine-HSA nanoparticles by desolvation method, they were well characterized by TEM, SEM, DLS, and FTIR techniques. Afterwards the interaction of HSA and the berberine was evaluated by molecular docking analysis. Finally, the antioxidant activity of the berberine-HSA nanoparticles against H2O2-induced oxidative stress in cultured neurons as a model of AD was evaluated by cellular assays. The results showed that the prepared berberine-HSA nanoparticles have a spherical-shaped morphology with a size of around 100 nm and zeta potential value of −31.84 mV. The solubility value of nanoparticles was calculated to be 40.27%, with a berberine loading of 19.37%, berberine entrapment efficiency of 70.34%, and nanoparticles yield of 88.91%. Also, it was shown that the berberine is not significantly released from HSA nanoparticles within 24 hours. Afterwards, molecular docking investigation revealed that berberine spontaneously interacts with HSA through electrostatic interaction. Finally, cellular assays disclosed that the pretreatment of neuronal cultures with berberine-HSA nanoparticles decreased the H2O2-stimulated cytotoxicity and relevant morphological changes and enhanced the CAT activity. In conclusion, it can be indicated that the nanoformulation of the berberine can be used as a promising platform for inhibition of oxidative damage-induced Alzheimer’s disease (AD).

scholarly journals Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

2020 ◽  
Vol 10 (12) ◽  
pp. 923
Author(s):  
Vandna Verma ◽  
Devendra Singh ◽  
Reeta KH
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Sinapic Acid ◽  
Neuronal Loss ◽  
Protective Effects ◽  
Cholinergic Dysfunction ◽  
Model Of Alzheimer’S Disease ◽  
Neuro Inflammation

The role of oxidative stress, neuro-inflammation and cholinergic dysfunction is already established in the development of Alzheimer’s disease (AD). Sinapic acid (SA), a hydroxylcinnamic acid derivative, has shown neuro-protective effects. The current study evaluates the neuro-protective potential of SA in intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in rats. Male Wistar rats were bilaterally injected with ICV-STZ. SA was administered intragastrically once daily for three weeks. Rats were divided into sham, ICV-STZ, STZ + SA (10 mg/kg), STZ + SA (20 mg/kg) and SA per se (20 mg/kg). Behavioral tests were assessed on day 0 and 21 days after STZ. Later, rats were sacrificed for biochemical parameters, pro-inflammatory cytokines, choline acetyltransferase (ChAT) expression and neuronal loss in the CA1 region of the hippocampus. The results showed that SA 20 mg/kg significantly (p < 0.05) improved cognitive impairment as assessed by Morris water maze and passive avoidance tests. SA 20 mg/kg reinstated the altered levels of GSH, MDA, TNF-α and IL-1β in the cortex and hippocampus. STZ-induced decreased expression of ChAT and neuronal loss were also significantly (p < 0.05) improved with SA. Our results showed that SA exhibits neuro-protection against ICV-STZ induced oxidative stress, neuro-inflammation, cholinergic dysfunction and neuronal loss, suggesting its potential in improving learning and memory in patients of AD.

Sophocarpine Attenuates Cognitive Impairment and Promotes Neurogenesis in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Jian-Ya Ye ◽  
Qingmao Hao ◽  
Yijun Zong ◽  
Yongqing Shen ◽  
Zhiqin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Microglial Activation ◽  
Therapeutic Agent ◽  
Amyloid Β ◽  
Neuroprotective Effects ◽  
Model Of Alzheimer’S Disease ◽  
Inflammatory Processes ◽  
Inflammatory Changes

<b><i>Introduction:</i></b> Alzheimer’s disease (AD), which is characterized by abnormal deposition of amyloid-β (Aβ) plaques and impaired neurogenesis and cognition, still lacks an optimally effective therapeutic agent for its management, and mounting evidence has shown that inflammatory processes are implicated in AD. Sophocarpine has been reported to exert inflammation-regulating effects in various diseases. However, whether sophocarpine can exert anti-neuroinflammatory and neuroprotective effects in AD remains unclear. This study investigated whether sophocarpine could ameliorate the pathological features and potential mechanisms in a mouse AD model. <b><i>Methods:</i></b> APP/PS1 mice were treated with sophocarpine for 8 weeks. We quantified the effects of sophocarpine treatment on cognitive performance using a behavioral test. Brain Aβ deposits and neurogenesis were evaluated using immunofluorescence staining. We also assessed the morphology and inflammatory changes induced by sophocarpine administration and its expression in the hippocampus. <b><i>Results:</i></b> Administration of sophocarpine significantly alleviated cognitive impairment and reduced neural loss. APP/PS1 mice treated with sophocarpine showed reduced Aβ plaque deposits and enhanced neurogenesis. Sophocarpine markedly decreased the expression of inflammation markers and inhibited microglial activation. <b><i>Conclusions:</i></b> Sophocarpine could potentially alleviate cognitive impairment and brain damage in APP/PS1 mice with its neuroprotective effects via modulation of the inflammatory pathway.

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