scholarly journals Ginsenoside Rg1 Prevents Cognitive Impairment and Hippocampal Neuronal Apoptosis in Experimental Vascular Dementia Mice by Promoting GPR30 Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fengming Shen ◽  
Juan Wang ◽  
Feng Gao ◽  
Jingji Wang ◽  
Guoqi Zhu
Keyword(s):  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Neuronal Apoptosis ◽  
Mrna Level ◽  
Neuronal Loss ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ginsenoside Rg1 ◽  
Behavioral Tests ◽  
Bilateral Common Carotid Artery ◽  
G Protein Coupled

This study is aimed at investigating the potential roles of G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) in the preventive effect of ginsenoside Rg1 against cognitive impairment and hippocampal cell apoptosis in experimental vascular dementia (VD) in mice. The effects of bilateral common carotid artery stenosis (BCAS) on GPR30 expression at mRNA level were evaluated. Thereafter, the BCAS mouse model was utilized to evaluate the protection of Rg1 (0.1, 1, 10 mg/kg, 14 days, ip). Spatial memory was evaluated by water Morris Maze 7 days post BCAS. After behavioral tests, neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and potential mechanisms were determined using western blotting and quantitative real-time PCR. Our results showed that GPR30 expression in the hippocampal region at mRNA level was promoted 30 min, 3 h, 6 h, and 24 h following BCAS. Ginsenoside Rg1 (1 or 10 mg/kg, 14 days, ip) promoted GPR30 expression in the hippocampus of model mice (after behavioral tests) but did not alter GPR30 expression in the hippocampus of control mice. Moreover, treatment of ginsenoside Rg1 (10 mg/kg) or G1 (5 μg/kg), a GPR30 agonist, prevented BCAS-induced memory impairment and hippocampal neuronal loss and apoptosis and promoted the ratio of Bcl-2 to Bax expression in the hippocampus (after behavioral tests). On the contrary, G15 (185 μg/kg), an antagonist of GPR30, aggravated BCAS-induced hippocampal neuronal loss and apoptosis. Finally, drug-target molecular docking pointed that Rg1 had a lower binding energy with GPR30 compared with Bax and Bcl-2. Together, our data implicate that ginsenoside Rg1 prevents cognitive impairment and hippocampal neuronal apoptosis in VD mice, likely through promoting GPR30 expression. These results would provide important implications for the application of Rg1 in the treatment of VD.

Motor neuronal and glial apoptosis in the adult facial nucleus after intracranial nerve transection

2006 ◽  
Vol 104 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Per Mattsson ◽  
Kioumars Delfani ◽  
Ann Marie Janson ◽  
Mikael Svensson
Keyword(s):  
Facial Nerve ◽  
Motor Neurons ◽  
Neuronal Apoptosis ◽  
Neuronal Loss ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cresyl Violet ◽  
Nerve Transection ◽  
Facial Nucleus ◽  
Double Labeling ◽  
Intracranial Lesions

Object Intracranial lesions affecting the facial nerve are usually associated with significant morbidity and poor functional restitution, despite the fact that a peripheral nerve injury normally recovers well. Mechanistic explanations are needed to direct future therapies. Although neonatal motor neurons are known to die as a result of apoptosis after axotomy, this cell death mechanism has not been explicitly demonstrated after peripheral cranial nerve transection in adult mammals. Methods The authors induced substantial retrograde neuronal death in the adult rodent by transecting the facial nerve during its intracranial course. Neuronal apoptosis was demonstrated as shrunken facial motor neurons, retrogradely labeled with fluorogold and with nuclei positively labeled by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick–end labeling (TUNEL). Glial apoptosis was demonstrated by double labeling with respect to cell type. On postinjury Days 7 and 14, the intracranial axotomy led to neuronal apoptosis, corresponding to a neuronal loss that was observed quantitatively in cresyl violet–stained tissue sections obtained using a stereological method. In contrast, no neuronal apoptosis was observed after creating a distal lesion of the facial nerve, which causes less neuronal loss. In addition, glial apoptosis was seen in the facial nucleus after both distal and proximal axotomy. Whereas the proximal intracranial axotomy led to TUNEL-positive nuclei in cells showing markers for oligodendrocytes and microglia, only the latter glial cell population was double labeled with TUNEL-positive nuclei after distal lesioning. Conclusions These findings may ultimately lead to new therapeutic strategies in patients suffering from facial nerve palsy due to an intracranial lesion.

scholarly journals AIM2 Inflammasome Mediates Hallmark Neuropathological Alterations and Cognitive Impairment in a Mouse Model of Vascular Dementia

2020 ◽  
Author(s):  
Luting Poh ◽  
David Y. Fann ◽  
Peiyan Wong ◽  
Hong Meng Lim ◽  
Sok Lin Foo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Vascular Dementia ◽  
Cell Activation ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Glial Cell Activation

AbstractChronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the innate immune response – particularly the inflammasome signaling pathway. Comprehensive analyses revealed that chronic cerebral hypoperfusion induces a complex temporal expression and activation of inflammasome components and their downstream products (IL-1β and IL-18) in different brain regions, and promotes activation of apoptotic and pyroptotic cell death pathways. Polarized glial cell activation, white matter lesion formation and hippocampal neuronal loss also occurred in a spatiotemporal manner. Moreover, in AIM2 knockout mice we observed attenuated inflammasome-mediated production of proinflammatory cytokines, apoptosis and pyroptosis, as well as resistance to chronic microglial activation, myelin breakdown, hippocampal neuronal loss, and behavioural and cognitive deficits following BCAS. Hence, we have demonstrated that activation of the AIM2 inflammasome substantially contributes to the pathophysiology of chronic cerebral hypoperfusion-induced brain injury and may therefore represent a promising therapeutic target for attenuating cognitive impairment in VaD.

scholarly journals Electroacupuncture inhibits hippocampal neuronal apoptosis and improves cognitive dysfunction in mice with vascular dementia via modulating JNK signaling pathway

2021 ◽  
Author(s):  
Yaru Liu ◽  
Chunyan Li ◽  
Zhenyang Yan ◽  
Yafei Ren ◽  
Woyu Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effects ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Dependent Pathway

Abstract Background: Nerve cell apoptosis is an important pathological mechanism of vascular dementia (VaD). There are evidences that Electroacupuncture (EA) can reduce cognitive impairment in VaD patients and protect nerve cells. However, the mechanism remains unknown. JNK signaling pathway play an important role in apoptosis. And JNK induces cell apoptosis in two main ways, namely JNK transcription-dependent pathway and JNK transcription-independent route. We focus on whether EA can inhibit apoptosis and alleviate cognitive impairment by regulating JNK signaling pathway.Method: In this study, Bilateral common carotid artery clipping (BCCAo) was used as a method to establish VaD mouse model. Longa scoring method and Morris water maze were used to evaluate whether EA could improve the behavioral score of VaD mice. The neuroprotective effects of EA were evaluated by the Hematoxylin and Eosin (HE) staining, TUNEL and Flow Cytometry (FCM). Western blot and real-time PCR were used to detect the expression of JNK-3, AP-1, P53, Bcl -2, Bax, and Caspase-3.Results: Our findings indicated that EA could improve the behavioral scores of VaD mice. VaD mice treated with EA reduced hippocampal neuronal apoptosis. In addition, EA could reduce the expression of JNK-3, AP-1, P53, Bax and Caspase-3 proteins and mRNA in the hippocampus of VaD mice, and increase the expression of Bcl-2.Conclusion: Our findings suggested that the mechanism of action of EA to treat VaD may be related to its regulation of JNK transcription-dependent pathway and JNK transcription-independent route.

Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

2020 ◽  
Author(s):  
Amteshwar Singh Jaggi
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Vascular Dementia ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Cerebral Ischemic ◽  
The Brain

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

Pharmacological Inhibition of Transient Receptor Potential Melastatin 2 (TRPM2) Channels Attenuates Diabetes-induced Cognitive Deficits in Rats: A Mechanistic Study

2020 ◽  
Vol 17 (3) ◽  
pp. 249-258 ◽  
Author(s):  
Pavan Thapak ◽  
Mahendra Bishnoi ◽  
Shyam S. Sharma
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Ache Activity ◽  
Transient Receptor Potential ◽  
Mrna Level ◽  
Receptor Potential ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channels ◽  
Transient Receptor ◽  
Gsk 3Β

Background: Diabetes is a chronic metabolic disorder affecting the central nervous system. A growing body of evidence has depicted that high glucose level leads to the activation of the transient receptor potential melastatin 2 (TRPM2) channels. However, there are no studies targeting TRPM2 channels in diabetes-induced cognitive decline using a pharmacological approach. Objective: The present study intended to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB), a TRPM2 inhibitor, in diabetes-induced cognitive impairment. Methods: Streptozotocin (STZ, 50 mg/kg, i.p.) was used to induce diabetes in rats. Animals were randomly divided into the treatment group, model group and age-matched control and pre se group. 2-APB treatment was given for three weeks to the animals. After 10 days of behavioural treatment, parameters were performed. Animals were sacrificed at 10th week of diabetic induction and the hippocampus and cortex were isolated. After that, protein and mRNA expression study was performed in the hippocampus. Acetylcholinesterase (AchE) activity was done in the cortex. Results: : Our study showed the 10th week diabetic animals developed cognitive impairment, which was evident from the behavioural parameters. Diabetic animals depicted an increase in the TRPM2 mRNA and protein expression in the hippocampus as well as increased AchE activity in the cortex. However, memory associated proteins were down-regulated, namely Ca2+/calmodulin-dependent protein kinase II (CaMKII-Thr286), glycogen synthase kinase 3 beta (GSK-3β-Ser9), cAMP response element-binding protein (CREB-Ser133), and postsynaptic density protein 95 (PSD-95). Gene expression of parvalbumin, calsequestrin and brain-derived neurotrophic factor (BDNF) were down-regulated while mRNA level of calcineurin A/ protein phosphatase 3 catalytic subunit alpha (PPP3CA) was upregulated in the hippocampus of diabetic animals. A three-week treatment with 2-APB significantly ameliorated the alteration in behavioural cognitive parameters in diabetic rats. Moreover, 2-APB also down-regulated the expression of TRPM2 mRNA and protein in the hippocampus as well as AchE activity in the cortex of diabetic animals as compared to diabetic animals. Moreover, the 2-APB treatment also upregulated the CaMKII (Thr-286), GSK-3β (Ser9), CREB (Ser133), and PSD-95 expression and mRNA levels of parvalbumin, calsequestrin, and BDNF while mRNA level of calcineurin A was down-regulated in the hippocampus of diabetic animals. Conclusion: : This study confirms the ameliorative effect of TRPM2 channel inhibitor in the diabetes- induced cognitive deficits. Inhibition of TRPM2 channels reduced the calcium associated downstream signaling and showed a neuroprotective effect of TRPM2 channels in diabetesinduced cognitive impairment.

The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

2019 ◽  
pp. 574-599
Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Structure And Function ◽  
Vascular Risk Factors ◽  
Vascular Health ◽  
Vascular Risk ◽  
And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

scholarly journals 421 - Mood disorders and its relationship with cognitive impairment and dementia

2020 ◽  
Vol 32 (S1) ◽  
pp. 137-137
Author(s):  
Sandra Torres ◽  
Andreia Lopes
Keyword(s):  
Cognitive Impairment ◽  
Mood Disorders ◽  
Neuronal Loss ◽  
Neurocognitive Impairment ◽  
Attention And Memory ◽  
Psychiatric Illnesses ◽  
Neurocognitive Functions ◽  
The Many ◽  
The One ◽  
Published Research

ABSTRACT:Mood disorders are common psychiatric illnesses that represent a major cause of disability worldwide. With life expectancy and the percentage of elderly people rising in many developed and undeveloped countries around the globe, cognitive impairment and dementia are gaining a societal importance. The relation between mood disorders and cognitive function is a twofold. On the one hand, cognitive deficits within mood disorders have been studied extensively, in which there seems to be a persistent neurocognitive impairment, both in acute phases and in interepisodic euthymic phases. Although results have not always been consistent, an overall pattern of specific impairments – in executive function, attention and memory - has become evident. On the other hand, recent research suggests that mood disorders, in general, may be risk factors for the development of mild cognitive impairment and dementia. In this sense, of the many models for the association of mood disorders and dementia, two are favored by several authors. One suggests that mood disorders are a risk factor for earlier clinical manifestation of dementia. The second sees mood disorders as the cause of dementing states, for instance through neuronal loss via dysregulation of the glucocorticoid cascade. In fact, there is suggestion that impairment of neuroplasticity may underlie the pathophysiology of mood disorders as such, and not only of neurocognitive impairment. In some patients, specific neurocognitive functions may be present before the onset of mood disorder and may constitute a trait factor or even an endophenotype. The aim of the present work is to, through a basic narrative review of published research on the main databases, summarize the main evidences of the association of mood disorders and dementia.

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