scholarly journals Soluble epoxide hydrolase inhibition improves cognitive function and parenchymal artery dilation in a hypertensive model of chronic cerebral hypoperfusion

2020 ◽  
Author(s):  
Nusrat Matin ◽  
Courtney Fisher ◽  
Theresa A. Lansdell ◽  
Bruce D. Hammock ◽  
Jun Yang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

Neurorestorative effects of epigallocatechin-3-Gallate on cognitive function in a chronic cerebral hypoperfusion rat model

2016 ◽  
Vol 34 (3) ◽  
pp. 367-377 ◽  
Author(s):  
Jae-Young Han ◽  
Jung-Kook Kim ◽  
Jae-Hong Kim ◽  
Bong-Seok Oh ◽  
Wan-Ju Cho ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Rat Model ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

scholarly journals The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both In Vivo and In Vitro Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of Aβ and Autophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Yan Liu ◽  
Xiaobo Huang ◽  
Wenqiang Chen ◽  
Yujing Chen ◽  
Ningqun Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Hippocampal Neurons ◽  
The Elderly ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Dependent Manner ◽  
Active Ingredients ◽  
Related Proteins

Chronic cerebral hypoperfusion (CCH) is closely related to the occurrence of Alzheimer’s disease (AD) in the elderly. CCH can induce overactivation of autophagy, which increases the deposition of amyloid-β (Aβ) plaques in the brain, eventually impairing the cognitive function. Yuan-Zhi decoction (YZD) is a traditional Chinese medicine (TCM) formulation that is used to treat cognitive dysfunction in the elderly, but the specific mechanism is still unclear. In this study, we simulated CCH in a rat model through bilateral common carotid artery occlusion (BCCAO) and treated the animals with YZD. Standard neurological tests indicated that YZD significantly restored the impaired cognitive function after BCCAO in a dose-dependent manner. Furthermore, YZD also decreased the levels of Aβ aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An in vitro model of CCH was also established by exposing primary rat hippocampal neurons to hypoxia and hypoglycemia (H-H). YZD and its active ingredients increased the survival of these neurons and decreased the levels of Aβ1-40 and Aβ1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both Aβ aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets Aβ, autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.

scholarly journals Ameliorating Effects of Ethanol Extract ofFructus mumeon Scopolamine-Induced Memory Impairment in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Min-Soo Kim ◽  
Won Kyung Jeon ◽  
Kye Wan Lee ◽  
Yu Hwa Park ◽  
Jung-Soo Han
Keyword(s):  
Cognitive Function ◽  
Morris Water Maze ◽  
Water Maze ◽  
Memory Impairment ◽  
Cholinergic Neurons ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Memory Impairments ◽  
Morris Water Maze Task ◽  
Increased Activity

We previously reported thatFructus mume(F. mume) extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whetherF. mumeextracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments.F. mume(50, 100, or 200 mg/kg) was administered to C57BL/6 mice for 14 days (days 1–14) and memory impairment was induced by scopolamine (1 mg/kg), a muscarinic receptor antagonist for 7 days (days 8–14). Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that receivedF. mumeand scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments ofF. mumeincreased ChAT expression in the hippocampus. These results indicated thatF. mumemight enhance cognitive function via action of cholinergic neurons.

scholarly journals Epoxy fatty acid dysregulation and neuroinflammation in Alzheimer’s disease is resolved by a soluble epoxide hydrolase inhibitor

2020 ◽  
Author(s):  
Anamitra Ghosh ◽  
Michele E. Comerota ◽  
Debin Wan ◽  
Fading Chen ◽  
Nicholas E. Propson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Fatty Acids ◽  
Cognitive Function ◽  
Mouse Models ◽  
Small Molecule ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Epoxy Fatty Acids ◽  
5Xfad Mouse ◽  
Β Amyloid

AbstractNeuroinflammation has been increasingly recognized to play critical roles in Alzheimer’s disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by the soluble epoxide hydrolase (sEH). We found that sEH is predominantly expressed in astrocytes where its levels are significantly elevated in postmortem human AD brains and in β-amyloid mouse models, and the latter is correlated with drastic reductions of brain EpFA levels. Using a highly potent and specific small molecule sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), we report here that TPPU treatment potently protected against LPS-induced inflammation in vitro and in vivo. Long-term administration of TPPU to the 5xFAD mouse model via drinking water reversed microglia and astrocyte reactivity and immune pathway dysregulation, and this is associated with reduced β–amyloid pathology and improved synaptic integrity and cognitive function. Importantly, TPPU treatment reinstated and positively correlated EpFA levels in the 5xFAD mouse brain, demonstrating its brain penetration and target engagement. These findings support TPPU as a novel therapeutic target for the treatment of AD and related disorders.One Sentence SummaryWe show that soluble epoxide hydrolase is upregulated in AD patients and mouse models, and that inhibition of this lipid metabolic pathway using an orally bioavailable small molecule inhibitor is effective in restoring brain epoxy fatty acids, ameliorating AD neuropathology and improving synaptic and cognitive function.

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