scholarly journals Dendritic complexity change in the triple transgenic mouse model of Alzheimer’s disease

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8178
Author(s):  
Yu Zhang ◽  
Zhenlong Xiao ◽  
Zhijun He ◽  
Junyu Chen ◽  
Xin Wang ◽  
...  

Alzheimer’s disease (AD) is an irreversible, neurodegenerative disease that is characterized by memory impairment and executive dysfunction. However, the change of fine structure of neuronal morphology remains unclear in the AD model mouse. In this study, high-resolution mouse brain sectional images were scanned by Micro-Optical Sectioning Tomography (MOST) technology and reconstructed three-dimensionally to obtain the pyramidal neurons. The method of Sholl analysis was performed to analyze the neurons in the brains of 6- and 12-month-old AD mice. The results showed that dendritic complexity was not affected in the entorhinal cortex between 6-month-old mice and 12-month-old mice. The dendritic complexity had increased in the primary motor cortex and CA1 region of hippocampus of 12- month-old mice compared with 6-month-old mice. On the contrary, dendritic complexity in the prefrontal cortex was decreased significantly between 6-month-old and 12-month-old mice. To our knowledge, this is the first study to provide high-resolution brain images of triple transgenic AD mice for statistically analyzing neuronal dendrite complexity by MOST technology to reveal the morphological changes of neurons during AD progression.

2021 ◽  
Vol 11 (11) ◽  
pp. 1423
Author(s):  
Zackary Bowers ◽  
Panchanan Maiti ◽  
Ali Bourcier ◽  
Jarod Morse ◽  
Kenneth Jenrow ◽  
...  

Combined treatments using polyphenols and omega fatty acids provide several therapeutic benefits for a variety of age-related disorders, including Alzheimer’s disease (AD). Previously, we found a commercial product, Total Body Rhythm (TBR), consisting of tart cherry extract, a potent polyphenol, and omega fatty acids, significantly reduced memory, and neuropathological deficits in the 192 IgG-saporin mouse model of AD. The present study assessed the efficacy of TBR for treating behavioral and neuropathological deficits in the 5xFAD model of AD. Both 6- and 12-month-old 5xFAD mice and age-matched wild-type controls received TBR (60 mg/kg) or the equivalent dose of vehicle (0.5% methylcellulose) via oral administration, every other day for two months. All mice were tested in the open field (OF), novel object recognition (NOR), and the Morris water maze (MWM) tasks. In addition, neuronal morphology, neurodegeneration, Aβ plaque load, and glial activation were assessed. TBR treatment reduced memory deficits in the MWM and NOR tests and lessened anxiety levels in the OF task, mostly in the 6-month-old male mice. TBR also protected against neuron loss, reduced activation of astrocytes and microglia, primarily in 6-month-old mice, and attenuated Aβ deposition. These results suggest that the combination of tart cherry extract and omega fatty acids in TBR can reduce AD-like deficits in 5xFAD mice.


2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Anna Papazoglou ◽  
Julien Soos ◽  
Andreas Lundt ◽  
Carola Wormuth ◽  
Varun Raj Ginde ◽  
...  

Alzheimer’s disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study an APPswePS1dE9 AD mouse model has been analyzed using implantable video-EEG radiotelemetry to perform long-term EEG recordings from the primary motor cortex M1 and the hippocampal CA1 region in both genders. Besides motor activity, EEG recordings were analyzed for electroencephalographic seizure activity and frequency characteristics using a Fast Fourier Transformation (FFT) based approach. Automatic seizure detection revealed severe electroencephalographic seizure activity in both M1 and CA1 deflection in APPswePS1dE9 mice with gender-specific characteristics. Frequency analysis of both surface and deep EEG recordings elicited complex age, gender, and activity dependent alterations in the theta and gamma range. Females displayed an antithetic decrease in theta (θ) and increase in gamma (γ) power at 18-19 weeks of age whereas related changes in males occurred earlier at 14 weeks of age. In females, theta (θ) and gamma (γ) power alterations predominated in the inactive state suggesting a reduction in atropine-sensitive type II theta in APPswePS1dE9 animals. Gender-specific central dysrhythmia and network alterations in APPswePS1dE9 point to a functional role in behavioral and cognitive deficits and might serve as early biomarkers for AD in the future.


2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Brikena Hoxha ◽  
Nicholas Talley ◽  
Miranda Anderson ◽  
Mustafa Alkhouli ◽  
Michaela Squire ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 944
Author(s):  
Alejandro R. Roda ◽  
Gisela Esquerda-Canals ◽  
Joaquim Martí-Clúa ◽  
Sandra Villegas

Clinical symptoms of Alzheimer’s Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2.5 months old and cognitive impairment in between 3- and 5-month-old mice. In this work, the effect of chronic Aβ-immunotherapy on behavioral and cognitive abilities was tested by monthly administering the antibody fragment scFv-h3D6 to 3xTg-AD female mice from 5 to 9 months of age. An untreated group was used as a reference, as well as to attain some information on the effect of training during the longitudinal study. Behavioral and psychological symptoms of dementia (BPSD)-like symptoms were already evident in 5-month-old mice, in the form of neophobia and anxious-like behavior. The exploratory activity decreased over the longitudinal study, not only for 3xTgAD mice but also for the corresponding non-transgenic mice (NTg). Learning abilities of 3xTg-AD mice were not seriously compromised but an impairment in long-term spatial memory was evident at 5 months of age. Interestingly, scFv-h3D6-treatment affected the cognitive impairment displayed by 5-month-old 3xTg-AD mice. It is worth noting that training also reduced cognitive impairment of 3xTg-AD mice over the longitudinal study, suggesting that to properly quantify the isolated therapeutic potential of any drug on cognition using this model it is convenient to perform a prompt, age-matched study rather than a longitudinal study. In addition, a combination of both training and Aβ-immunotherapy could constitute a possible approach to treat Alzheimer’s disease.


2011 ◽  
Vol 7 ◽  
pp. S391-S392
Author(s):  
Juliet Moncaster ◽  
Noel Casey ◽  
Timothy Connelly ◽  
Mark Wojnarowicz ◽  
Olga Minaeva ◽  
...  

2021 ◽  
Vol 17 (6) ◽  
pp. 1088-1097
Author(s):  
Yaohui Zhang ◽  
Lixiang Wang ◽  
Guichen Li ◽  
Jianyuan Gao

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).


2001 ◽  
Vol 38-40 ◽  
pp. 1477-1487 ◽  
Author(s):  
Slawomir J. Nasuto ◽  
Robert M. Knape ◽  
Jeffrey L. Krichmar ◽  
Giorgio A. Ascoli

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