Dynamic Control of Dendritic mRNA Expression by CNOT7 Regulates Synaptic Efficacy and Higher Cognitive Function

Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the β-amyloid (Aβ) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5 % cholesterol; the high cholesterol+low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5 % cholesterol and 2 % Oriental plum powder; and the high cholesterol+high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5 % cholesterol and 5 % Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aβ and β-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aβ and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.

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Exercise Training Ameliorates Cognitive Dysfunction in Amyloid Beta-injected Rat Model: Possible Mechanisms of Angiostatin/VEGF Signaling

10.21203/rs.3.rs-214291/v1 ◽

2021 ◽

Author(s):

ALIASGHAR Zarezadehmehrizi ◽

Junyoung Hong ◽

Jong-hae Lee ◽

Hamid Rajabi ◽

Reza Gharakhanlou ◽

...

Keyword(s):

Cognitive Function ◽

Exercise Training ◽

Mrna Expression ◽

Expression Level ◽

Male Rats ◽

Mrna Levels ◽

Mrna Expression Level ◽

Vegf Signaling ◽

Intrahippocampal Injection ◽

Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer’s disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD are incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aβ (AD), and AD-exercise (AD-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of HIF-1, VEGF, VEGFR2, and angiostatin were determined by RT-PCR. We found that cognitive function was impaired in AD rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from AD rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from AD rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in AD, possibly through enhancing VEGF signaling and reducing angiostatin.

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Effects of Resistance Exercise on mRNA Expression of Brain Neuroplasticity Related Factors in Hippocampus and Cognitive Function in Ovariectomized Rats

Institute of Brain-based Education Korea National University of Education ◽

10.31216/bdl.20210037 ◽

2021 ◽

Vol 11 (4) ◽

Keyword(s):

Cognitive Function ◽

Resistance Exercise ◽

Mrna Expression ◽

Ovariectomized Rats ◽

Related Factors

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A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction

Current Pharmaceutical Design ◽

10.2174/1381612826666200415171622 ◽

2020 ◽

Vol 26 (34) ◽

pp. 4330-4337

Author(s):

Jennifer Gile ◽

Yoshimasa Oyama ◽

Sydney Shuff ◽

Tobias Eckle

Keyword(s):

Cognitive Function ◽

Mrna Expression ◽

Cognitive Dysfunction ◽

Critical Role ◽

Underlying Mechanism ◽

Mrna Levels ◽

Expression Levels ◽

Inflammatory Phenotype ◽

Dependent Learning ◽

Mrna Expression Levels

Background: We recently reported a role for the circadian rhythm protein Period 2 (PER2) in midazolam induced cognitive dysfunction. Based on previous studies showing a critical role for the adenosine A2B receptor (ADORA2B) in PER2 regulation, we hypothesized that hippocampal ADORA2B is crucial for cognitive function. Methods: Midazolam treated C57BL/6J mice were analyzed for Adora2b hippocampal mRNA expression levels, and spontaneous T-maze alternation was determined in Adora2b-/- mice. Using the specific ADORA2B agonist BAY-60-6583 in midazolam treated C57BL/6J mice, we analyzed hippocampal Per2 mRNA expression levels and spontaneous T-maze alternation. Finally, Adora2b-/- mice were assessed for mRNA expression of markers for inflammation or cognitive function in the hippocampus. Results: Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in Adora2b-/- mice. ADORA2B agonist BAY-60-6583 restored midazolam mediated reduction in spontaneous alternation in C57BL/6J mice. Analysis of hippocampal Tnf-α or Il-6 mRNA levels in Adora2b-/- mice did not reveal an inflammatory phenotype. However, C-fos, a critical component of hippocampus-dependent learning and memory, was significantly downregulated in the hippocampus of Adora2b-/- mice. Conclusion: These results suggest a role of ADORA2B in midazolam induced cognitive dysfunction. Further, our data demonstrate that BAY-60-6583 treatment restores midazolam induced cognitive dysfunction, possibly via increases of Per2. Additional mechanistic studies hint towards C-FOS as another potential underlying mechanism of memory impairment in Adora2b-/- mice. These findings suggest the ADORA2B agonist as a potential therapy in patients with midazolam induced cognitive dysfunction.

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