scholarly journals Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

2020 ◽  
Vol 10 ◽  
pp. 204512532091665 ◽  
Author(s):  
Dmitriy Matveychuk ◽  
Rejish K. Thomas ◽  
Jennifer Swainson ◽  
Atul Khullar ◽  
Mary-Anne MacKay ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Therapeutic Potential ◽  
Predictive Biomarkers ◽  
Major Depressive ◽  
Delayed Effects ◽  
Current State ◽  
Resistant Depression ◽  
The 1960S ◽  
The Brain ◽  
Unique Mechanism

Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.

Epilogue

2021 ◽  
pp. 203-208
Author(s):  
Walter Glannon
Keyword(s):  
Cognitive Functions ◽  
Therapeutic Potential ◽  
Functional Independence ◽  
Shared Control ◽  
Loss Of Control ◽  
Neural Prosthetics ◽  
Current State ◽  
The People ◽  
Sensory Motor ◽  
The Brain

This section summarizes the main neuroscientific and philosophical issues regarding neural prosthetics. It comments on the therapeutic potential of more and less invasive systems to restore sensory, motor, and cognitive functions. It also speculates on future neural prosthetics and how they might change our view of the brain–mind relation and our concept of ourselves as humans. The current state of neural prosthetics does not indicate that machines and implants control the thought and behaviour of people to whom they are connected or in whom they are implanted. There is no loss of control but shared control between these artificial systems and the people who use them. The rehabilitative and restorative capacity of neural prosthetics enable those with neurological or physical disabilities to acquire or regain functional independence.

scholarly journals Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model

2021 ◽  
Vol 14 (8) ◽  
pp. 737
Author(s):  
Vasily A. Aleshin ◽  
Anastasia V. Graf ◽  
Artem V. Artiukhov ◽  
Alexandra I. Boyko ◽  
Alexander L. Ksenofontov ◽  
...  
Keyword(s):  
Sex Differences ◽  
Therapeutic Potential ◽  
Dose Dependence ◽  
Female Rats ◽  
Male Rats ◽  
Long Term Effects ◽  
Pyridoxal Kinase ◽  
Delayed Effects ◽  
The Brain ◽  
Physiological And Biochemical

The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

scholarly journals Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

2010 ◽  
Vol 2 (4) ◽  
pp. 139-153 ◽  
Author(s):  
Danuta Jantas
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Cellular Mechanisms ◽  
Current State ◽  
Wide Range ◽  
Locomotive Activity ◽  
Trh Analogues ◽  
Cortical System ◽  
The Brain

SummaryThe physiological role of thyreoliberin (TRH) is the preservation of homeostasis within four systems (i) the hypothalamic-hypophsysiotropic neuroendocrine system, (ii) the brain stem/midbrain/spinal cord system, (iii) the limbic/cortical system, and (iv) the chronobiological system. Thus TRH, via various cellular mechanisms, regulates a wide range of biological processes (arousal, sleep, learning, locomotive activity, mood) and possesses the potential for unique and widespread applications for treatment of human illnesses. Since the therapeutic potential of TRH is limited by its pharmacological profile (enzymatic instability, short half-life, undesirable effects), several synthetic analogues of TRH were constructed and studied in mono- or adjunct therapy of central nervous system (CNS) disturbances. The present article summarizes the current state of understanding of the physiological role of TRH and describes its putative role in clinical indications in CNS maladies with a focus on the action of TRH analogues.

From many to one: Meditation and the plasticity of the predictive mind

2020 ◽  
Author(s):  
Ruben Laukkonen ◽  
Heleen A Slagter
Keyword(s):  
Cognitive Enhancement ◽  
The Self ◽  
Predictive Processing ◽  
Focused Attention ◽  
Conceptual Processing ◽  
Current State ◽  
Contemplative Science ◽  
Open Monitoring ◽  
Living Organisms ◽  
The Brain

How profoundly can humans change their own minds? In this paper we offer a unifying account of meditation under the predictive processing view of living organisms. We start from relatively simple axioms. First, the brain is an organ that serves to predict based on past experience, both phylogenetic and ontogenetic. Second, meditation serves to bring one closer to the here and now by disengaging from anticipatory processes. We propose that practicing meditation therefore gradually reduces predictive processing, in particular counterfactual cognition—the tendency to construct abstract and temporally deep representations—until all conceptual processing falls away. Our Many- to-One account also places three main styles of meditation (focused attention, open monitoring, and non-dual meditation) on a single continuum, where each technique progressively relinquishes increasingly engrained habits of prediction, including the self. This deconstruction can also make the above processes available to introspection, permitting certain insights into one’s mind. Our review suggests that our framework is consistent with the current state of empirical and (neuro)phenomenological evidence in contemplative science, and is ultimately illuminating about the plasticity of the predictive mind. It also serves to highlight that contemplative science can fruitfully go beyond cognitive enhancement, attention, and emotion regulation, to its more traditional goal of removing past conditioning and creating conditions for potentially profound insights. Experimental rigor, neurophenomenology, and no-report paradigms combined with neuroimaging are needed to further our understanding of how different styles of meditation affect predictive processing and the self, and the plasticity of the predictive mind more generally.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

MDM2-p53 Interaction Inhibitors: The Current State-of-Art and Updated Patent Review (2010-Present)

2020 ◽  
Vol 14 (4) ◽  
pp. 324-369 ◽  
Author(s):  
Rafał Rusiecki ◽  
Jakub Witkowski ◽  
Joanna Jaszczewska-Adamczak
Keyword(s):  
Therapeutic Potential ◽  
Research Work ◽  
Academic Research ◽  
Tumor Suppressor P53 ◽  
Research Groups ◽  
Current State ◽  
Mouse Double Minute ◽  
Patent Review ◽  
Main Emphasis ◽  
Double Minute

Background: Mouse Double Minute 2 protein (MDM2) is a cellular regulator of p53 tumor suppressor (p53). Inhibition of the interaction between MDM2 and p53 proteins is a promising anticancer therapy. Objective: This updated patent review is an attempt to compile the research and achievements of the various researchers working on small molecule MDM2 inhibitors from 2010 to date. We provide an outlook into the future for therapy based on MDM2 inhibition by presenting an overview of the most relevant patents which have recently appeared in the literature. Methods: Literature and recent patents focusing on the anticancer potential of MDM2-p53 interaction inhibitors and its applications have been analyzed. We put the main emphasis on the most perspective compounds which are or were examined in clinical trials. Results: Literature data indicated that MDM2 inhibitors are therapeutically effective in specific types of cancer or non-cancer diseases. A great number of patents and research work around new MDM2- p53 interaction inhibitors, possible combinations, new indications, clinical regimens in previous years prove that this targeted therapy is in the scope of interest for many business and academic research groups. Conclusion: Novel MDM2 inhibitors thanks to higher potency and better ADME properties have shown effectiveness in preclinical and clinical development however the final improvement of therapeutic potential for MDM2 inhibitors might depend on the useful combination therapy and exploring new cancer and non-cancer indications.

scholarly journals Sex‐related effects in major depressive disorder: Results of the European Group for the Study of Resistant Depression

2021 ◽  
Author(s):  
Lucie Bartova ◽  
Markus Dold ◽  
Gernot Fugger ◽  
Alexander Kautzky ◽  
Marleen M. M. Mitschek ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Major Depressive ◽  
Resistant Depression ◽  
European Group

scholarly journals Biological Properties and Prospects for the Application of Eugenol—A Review

2021 ◽  
Vol 22 (7) ◽  
pp. 3671
Author(s):  
Magdalena Ulanowska ◽  
Beata Olas
Keyword(s):  
Body Weight ◽  
Aromatic Compound ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Biological Properties ◽  
Clove Oil ◽  
Current State ◽  
Potential Component ◽  
Anti Inflammatory ◽  
High Concentrations

Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases.

scholarly journals Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicolas Salvetat ◽  
Fabrice Chimienti ◽  
Christopher Cayzac ◽  
Benjamin Dubuc ◽  
Francisco Checa-Robles ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rna Editing ◽  
Whole Blood ◽  
Healthy Controls ◽  
Major Depressive ◽  
Suicide Attempters ◽  
Blood Samples ◽  
Depressed Patients ◽  
The Brain

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.

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