Potential Role of Extracellular CIRP in Alcohol-Induced Alzheimer’s Disease

Sharma, Archna; Wang, Haichao

doi:10.1007/s12035-020-02075-1

Cited by 15 publications

(16 citation statements)

References 126 publications

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“…All experiments were performed according to the guideline of the National Institutes of Health (NIH) and the Institutional Ethics Committee at the Islamic Azad University (Ethical code: IR.IAU.MSHD.REC.1397.061) for the care and the use of laboratory animals. The animals were randomly divided into 5 groups ( n = 7-8) including ( 1 ) the sham group, surgical stress is induced and received an injection of saline (2 μL; intracerebroventricular injection, icv) instead of Aβ, and also saline (0.5 mL; intraperitoneally, ip) as a vehicle was injected instead of 6 times treatment during the next 21 days; ( 2 ) the AD group received an injection of Aβ 1-42 (10 μg/2 μL, icv) and saline as a vehicle (0.5 mL, ip) instead of 6 times treatment during the next 21 days; ( 3 4 5 ) the AD + BVS20, AD + BVS40, and AD + BVS80 groups received an injection of Aβ 1-42 (10 μg/2 μL, icv) and 20, 40, and 80 mg/kg of BVS (ip) 6 times during the next 21 days, respectively. The saline and BVS were injected every 4 days.…”

Section: Methodsmentioning

confidence: 99%

“…(1) Central crossing, ( 2 ) central time, ( 3 ) peripheral crossing, ( 4 ) peripheral time, and ( 5 ) total crossing ( 25 26 ).…”

Section: Methodsmentioning

confidence: 99%

“…Alzheimer's disease (AD) is a progressive neurodegenerative and inflammatory disease that causes changes in cognition, memory, and behavior and is accompanied by symptoms such as depression, anxiety, and psychosis ( 1 ). AD is the costliest disease in society, the sixth cause of mortality in the US, and the second most prevalent disease, after heart failure, among the elderly ( 2 ). In this disease, the precipitation of amyloid-beta (Aβ) peptide in certain brain regions, including the hippocampus, results in neurological disorders and disruptions in the function of synapses ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

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Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

et al. 2020

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Background and purpose: Venenum Bufonis is a Chinese traditional medicine produced from the glandular secretions of toads that contain biogenic amines, which have anti-inflammatory properties. The present study aimed to examine the effect of Bufo viridis secretions (BVS) on anxiety and depression-like behavior and hippocampal senile plaques volume in an animal model of Alzheimer's disease (AD). Experimental approach: Thirty-eight male Wistar rats were used. AD was induced by amyloid-beta (Aβ 1-42 ) (10 μg/2 μL, intracerebroventricular injection, icv) and then BVS at 20, 40, and 80 mg/kg were injected intraperitoneally (ip) in six equal intervals over 21 days. Anxiety and depression-like behavior were assessed using behavioral tests including open field test (OFT), elevated plus maze (EPM), and forced swimming test (FST) 21 days after the surgery. The volume of senile plaques was assessed based on the Cavalieri principle. Findings/Results: Results of the OFT showed that the central crossing number and the time in the AD group were significantly decreased compared to the sham group ( P < 0.01 and P < 0.001, respectively). Also, the values of these two parameters significantly increased in the AD + BVS80 group than the AD group ( P < 0.05 and P < 0.001, respectively). The time spent in the closed arm in the EPM dramatically increased in the AD group compared to the sham group ( P < 0.05) and significantly decreased in the AD + BVS80 group compared to the AD group ( P < 0.05). Results of the FST indicated that immobility time had a reduction in the AD + BVS20 ( P < 0.01), AD + BVS40, and AD + BVS80 groups compared to the AD group ( P < 0.001). The volume of senile plaques in the hippocampus showed a reduction in the treatment groups in comparison with the AD group ( P < 0.001 for all). Conclusion and implications: Results revealed that BVS injection could improve symptoms of anxiety and depression and decrease senile plaques in the hippocampus in an animal model of AD.

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Section: Methodsmentioning

confidence: 99%

“…(1) Central crossing, ( 2 ) central time, ( 3 ) peripheral crossing, ( 4 ) peripheral time, and ( 5 ) total crossing ( 25 26 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

et al. 2020

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“…This relationship was thought to be J-shaped, suitable alcohol intake (<12.0 g/day) could protect against dementia (89,90), similar with the relationship between coffee intake and AD. It is not advisable to take excessive drinking in daily life, as for the heavy alcohol drinkers, extracellular coldinducible RNA-binding protein (eCIRP) might mediate tau phosphorylation, leading to the progression of alcohol-induced AD (91). After matured hop bitter acid supplementation from beer, improvement of cognitive status was confirmed in a randomized trial (92).…”

Section: Alcohol Consumptionmentioning

confidence: 99%

The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention

et al. 2021

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Mild Alzheimer’s disease is the leading cause of dementia, accounting for 50-70% of cases. Alzheimer’s disease is an irreversible neurodegenerative disease, which affects daily life activities and social functioning. As life expectancy increases and demographic ageing occurs, the global prevalence of Alzheimer’s disease is expected to continue to rise especially in developing countries, leading to a costly burden of disease. Alzheimer’s disease is a complex and multifactorial disorder that is determined by the interaction of genetic susceptibility and environmental factors across the life course. Epidemiological studies have identified potential modifiable risk and protective factors for Alzheimer’s disease prevention. Moreover, Alzheimer’s disease is considered to start decades earlier before clinical symptoms occur, thus interventions targeting several risk factors in non-demented elderly people even middle-aged population might prevent or delay Alzheimer’s disease onset. Here, we provide an overview of current epidemiological advances related to Alzheimer’s disease modifiable risk factors, highlighting the concept of early prevention.

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“…In particular, we have shown that cerebral ischemia and alcohol exposure induce microglial expression of CIRP and release of eCIRP, which then acts as a neuroin ammatory mediator causing neuronal damage and death [7,8]. Recently, we showed that eCIRP also mediates alcohol-induced regional metabolic hypoactivity and memory impairment [9,10] and has a potential to be a mediator of Alzheimer's disease associated with alcohol consumption [11]. But, the precise mechanism of how eCIRP causes neuronal injury is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons

Sharma

Jacob

Marambaud

et al. 2021

Preprint

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Extracellular cold-inducible RNA-binding protein (eCIRP) stimulates microglial inflammation causing neuronal damage during ischemic stroke and is a critical mediator of alcohol-induced cognitive impairment. However, the precise role of eCIRP in mediating neuroinflammation remains unknown. In this study, we report that eCIRP activates neurotoxic cyclin-dependent kinase-5 (Cdk5)/p25 through the induction of IL-6Rα/STAT3 pathway in neurons. Amyloid b (Aβ)-mediated neuronal stress, which is associated with Alzheimer’s disease, increased levels of eCIRP released from BV2 microglial cells. The released eCIRP levels from BV2 cells increased 3.2-fold upon stimulation with conditioned medium from Neuro-2a (N2a) cells containing Aβ compared to control N2a supernatant in a time-dependent manner. Stimulation of N2a cells and primary neurons with eCIRP upregulated the neuronal Cdk5 activator p25 expression in a dose- and time-dependent manner. eCIRP directly induced neuronal STAT3 phosphorylation and p25 increase via its novel receptor IL-6Rα. Next, we showed using surface plasmon resonance that eCIRP-derived peptide C23 inhibited the binding of eCIRP to IL-6Rα at 25 mM, with a 40-fold increase in equilibrium dissociation constant (Kd) value (from 8.08 x 10-8 M to 3.43 x 10-6 M), and completely abrogated the binding at 50 mM. Finally, C23 reversed the eCIRP-induced increase in neuronal STAT3 phosphorylation and p25 levels. In conclusion, the current study demonstrates that upregulation of neuronal IL-6Rα/STAT3/Cdk5 pathway is a key mechanism of eCIRP’s role in neuroinflammation and that C23 as a potent inhibitor of this pathway, has translational potential in neurodegenerative pathologies controlled by eCIRP.

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Potential Role of Extracellular CIRP in Alcohol-Induced Alzheimer’s Disease

Cited by 15 publications

References 126 publications

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention

Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons

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Potential Role of Extracellular CIRP in Alcohol-Induced Alzheimer’s Disease

Cited by 15 publications

References 126 publications

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid β

The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention

Extracellular CIRP&nbsp;Activates the IL-6Rα/STAT3/Cdk5 Pathway&nbsp;in Neurons

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Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons