Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

Abstract Alzheimerʼs disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunction. Glutamate (Glu) metabolism pathway mediated neurotoxicity is one of main factors causing memory impairment in AD. TWIK-related potassium channel-1 (TREK-1) exerts protective effect in brain ischemia, but the role of it in AD is unknown. In this study, the SAMP8 mice were used as an AD model, the age-matched SAMR1 mice as a control, we investigated the change trend of TREK-1 channel as well as AD related molecules in brains of SAMP8 mice and showed the expression levels of TREK-1 compensatory arose before 3 months of age, then began to decline. Meanwhile the levels of Tau and Glu increased with age while Ach level decreased over age. Next, using α-Linolenic acid (ALA) as an activator of TREK-1 channel, we showed that activation of TREK-1 channel improved the learning and memory deficits of SAMP8 mice aged in 6 months. Furthermore, we explored the possible mechanisms and found that the levels of molecules were closely related to the glutamate metabolism pathway. After the activation of TREK-1 channel, the damaged neurons and astrocyte were rescued, the levels of Glu and NMDAR were down-regulated, while the level of GLT-1 was up-regulated. These findings suggested that TREK-1 played the crucial role in the pathological progression of AD and activation of TREK-1 channel improved the cognitive deficits in SAMP8 mice which is mediated by Glu metabolism pathway. The TREK-1 potassium channel may be expected to be a new potential therapeutic target for AD.

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Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

10.1101/2020.05.20.106153 ◽

2020 ◽

Author(s):

Pengbo Shi ◽

Zhaosu Li ◽

Xing Xu ◽

Jiaxun Nie ◽

Dekang Liu ◽

...

Keyword(s):

Spatial Memory ◽

Cognitive Deficits ◽

Glutamate Uptake ◽

Cognitive Disorders ◽

Memory Deficits ◽

Therapeutic Interventions ◽

Therapeutic Effects ◽

Non Invasive ◽

The Brain

ABSTRACTMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.

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Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases

Frontiers in Physiology ◽

10.3389/fphys.2021.640700 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tingting Li ◽

Chao Yu ◽

Shougang Zhuang

Keyword(s):

Animal Models ◽

Therapeutic Target ◽

Renal Fibrosis ◽

Kidney Diseases ◽

Disease Model ◽

Kidney Injury ◽

Potential Therapeutic Target ◽

Over Expression ◽

Ezh2 Expression

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that catalyzes the addition of methyl groups to histone H3 at lysine 27, leading to gene silencing. Mutation or over-expression of EZH2 has been linked to many cancers including renal carcinoma. Recent studies have shown that EZH2 expression and activity are also increased in several animal models of kidney injury, such as acute kidney injury (AKI), renal fibrosis, diabetic nephropathy, lupus nephritis (LN), and renal transplantation rejection. The pharmacological and/or genetic inhibition of EZH2 can alleviate AKI, renal fibrosis, and LN, but potentiate podocyte injury in animal models, suggesting that the functional role of EZH2 varies with renal cell type and disease model. In this article, we summarize the role of EZH2 in the pathology of renal injury and relevant mechanisms and highlight EZH2 as a potential therapeutic target for kidney diseases.

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Jealousy delirium associated with memory deficits

Clinical Management Issues ◽

10.7175/cmi.v1i3.604 ◽

2007 ◽

Vol 1 (3) ◽

pp. 111-122

Author(s):

Orazio Zanetti ◽

Angela Tommasoni ◽

Giulia Lussignoli

Keyword(s):

Early Diagnosis ◽

Cognitive Deficits ◽

Daily Living ◽

Neurodegenerative Disorder ◽

Neuropsychiatric Symptoms ◽

Memory Deficits ◽

Prompt Treatment ◽

Memory Deterioration ◽

With Memory

Alzheimer’s disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioural disturbances. A correct and early diagnosis not only allows prompt treatment but can also give the person with Alzheimer’s and his family more time to arm themselves with knowledge about this type of dementia and the best way to live with the disease. The role of Family Physician is very important in early diagnosis: dementia may be suspected if memory deficits are exhibited during the medical history and physical examination. Information from the patient’s family members, friends and caregivers may also point to signs of dementia. We report a case of a 75-years-old man who was suffering from cognitive deficits and behavioural problems: the first disease symptom was a strong feeling of jealousy towards his wife.

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Role of IT in HRM: Opportunities and Challenges

PARIPEX-INDIAN JOURNAL OF RESEARCH ◽

10.15373/22501991/apr2014/51 ◽

2012 ◽

Vol 3 (4) ◽

pp. 159-160

Author(s):

Megha Vashishth ◽

Keyword(s):

Role Of It

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POLIVARIABILITY OF THE BASTARD MOTIF IN THE SHORT STORIES BY GUY DE MAUPASSANT: CHARACTER IN SEARCH OF SELF-IDENTIFICATION

LITERARY PROCESS methodology names trends ◽

10.28925/2412-2475.2018.11.2027 ◽

2018 ◽

pp. 20-27

Author(s):

Oksana Galchuk

Keyword(s):

Short Stories ◽

Short Story ◽

Social Institutions ◽

Point Of View ◽

Guy De Maupassant ◽

Traditional Values ◽

The Social ◽

Role Of It ◽

Structural Methods

The theme of illegitimacy Guy de Maupassant evolved in his works this article perceives as one of the factors of the author’s concept of a person and the plane of intersection of the most typical motifs of his short stories. The study of the author’s concept of a person through the prism of polivariability of the motif of a bastard is relevant in today’s revision of traditional values, transformation of the usual social institutions and search for identities, etc. The purpose of the study is to give a definition to the existence specifics of the bastard motif in the Maupassant’s short stories by using historical and literary, comparative, structural methods of analysis as dominant. To do this, I analyze the content, variability and the role of this motive in the formation of the Maupassant’s concept of a person, the author’s innovations in its interpretation from the point of view of literary diachrony. Maupassant interprets the bastard motif in the social, psychological and metaphorical-symbolic sense. For the short stories with the presentation of this motif, I suggest the typology based on the role of it in the structure of the work and the ideological and thematic content: the short stories with a motif-fragment, the ones with the bastard’s leitmotif and the group where the bastard motif becomes a central theme. The Maupassant’s interpretation of the bastard motif combines the general tendencies of its existence in the world’s literary tradition and individual reading. The latter is the result of the author’s understanding of the relevant for the era issues: the transformation of the family model, the interest in the theory of heredity, the strengthening of atheistic sentiments, the growth of frustration in the system of traditional social and moral values etc. This study sets the ground for a prospective analysis of the evolution the bastard motif in the short-story collections of different years or a comparative study of the motif in short stories and novels by Maupassant.

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