Effects of Donepezil on Oxidative Stress and Cognitive Impairments in a Mouse Model of Familial Hypercholesterolemia

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

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Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽

10.3390/biology10070622 ◽

2021 ◽

Vol 10 (7) ◽

pp. 622

Author(s):

Iswariyaraja Sridevi Gurubaran ◽

Hanna Heloterä ◽

Stephen Marry ◽

Ali Koskela ◽

Juha M. T. Hyttinen ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Macular Degeneration ◽

Complement Component ◽

Factor H ◽

Age Related Macular Degeneration ◽

Related Factor ◽

Complement Factor ◽

Age Related ◽

Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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Aberrant adenosine A2A receptor signaling contributes to neurodegeneration and cognitive impairments in a mouse model of synucleinopathy

Experimental Neurology ◽

10.1016/j.expneurol.2016.05.040 ◽

2016 ◽

Vol 283 ◽

pp. 213-223 ◽

Cited By ~ 22

Author(s):

Qidi Hu ◽

Xiangpeng Ren ◽

Ya Liu ◽

Zhihui Li ◽

Liping Zhang ◽

...

Keyword(s):

Mouse Model ◽

Cognitive Impairments ◽

Adenosine A2a Receptor ◽

Receptor Signaling ◽

A2a Receptor ◽

Adenosine A2a

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Cancer cachexia in a mouse model of oxidative stress

Journal of Cachexia Sarcopenia and Muscle ◽

10.1002/jcsm.12615 ◽

2020 ◽

Vol 11 (6) ◽

pp. 1688-1704 ◽

Cited By ~ 2

Author(s):

Jacob L. Brown ◽

Marcus M. Lawrence ◽

Bumsoo Ahn ◽

Parker Kneis ◽

Katarzyna M. Piekarz ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Cancer Cachexia

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Basic neuroscience O-BN001. Calotropis procera (ROOT) ameliorates functions regain and attenuates oxidative stress in a mouse model of sciatic nerve compression injury

Clinical Neurophysiology ◽

10.1016/j.clinph.2021.02.159 ◽

2021 ◽

Vol 132 (8) ◽

pp. e77

Author(s):

Ghulam Hussain ◽

Azhar Rasul ◽

Haseeb Anwar ◽

Shoaib Ahmad Malik ◽

Shamaila Zafar ◽

...

Keyword(s):

Oxidative Stress ◽

Sciatic Nerve ◽

Mouse Model ◽

Nerve Compression ◽

Calotropis Procera ◽

Compression Injury ◽

Nerve Compression Injury

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Protective effect of citicoline against aluminum-induced cognitive impairments in rats

Toxicology and Industrial Health ◽

10.1177/0748233716641869 ◽

2016 ◽

Vol 33 (4) ◽

pp. 308-317 ◽

Cited By ~ 9

Author(s):

Ahmed O Abdel-Zaher ◽

Mostafa M Hamdy ◽

Mahran S Abdel-Rahman ◽

Doaa H Abd El-hamid

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Passive Avoidance ◽

Morris Water Maze ◽

Cognitive Deficits ◽

Aluminum Chloride ◽

Water Maze ◽

Cognitive Impairments ◽

Radial Arm Maze ◽

Time Required

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

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