scholarly journals Neurotrophins and Neurotrophic Therapy (Based on the Cerebrolysin Model) in the Treatment of Elderly Patients with Cognitive Disorders and Depression. Part 2

Psychiatry ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 80-89
Author(s):  
S. I. Gavrilova ◽  
T. P. Safarova
Keyword(s):  
Molecular Mechanisms ◽  
Common Mental Disorders ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Therapeutic Approaches ◽  
Neurodegenerative Process ◽  
Target Drug ◽  
Higher Doses ◽  
The Brain ◽  
Neurotrophic Therapy

Background: сognitive impairment and late depression, along with dementia, are the most common mental disorders in elderly and senile patients. Currently, more and more attention is being paid to preventive therapeutic approaches in the treatment of these conditions and to the study of drugs with multimodal neuroprotective and neurotrophic properties that contribute to the strengthening of the so-called endogenous system of protection and recovery of the brain, which is a kind of barrier to the incipient neurodegeneration. Objective: to present a review of domestic and foreign modern studies devoted to the study of the multimodal effects of the drug cerebrolysin, which has neurotrophin-like properties, and the results of its use in the treatment of cognitive disorders that do not reach the degree of dementia, as well as late depression. Material and methods: using the keywords “late age, mild cognitive disorders, depression, MCI syndrome, therapy, cerebrolysin”, we searched for scientifi c articles in the MEDLINE and PubMed databases for the period 2000–2020. Conclusion: the data presented in the review showed that cerebrolysin, acting as a multi-target drug, affects multiple molecular mechanisms of the pathogenesis of pre-dementia cognitive disorders and late-age depression. The drug detects a neurotrophin-like effect, improves the processes of neuroplasticity and can help enhance the protection and restoration of the brain under various pathological infl uences. Neurobiological studies and the results of a pilot prospective study indicate the preventive potential of cerebrolysin in preventing the development or slowing the progression of the neurodegenerative process of Alzheimer’s type. In the studies presented in the review, the ability of cerebrolysin to increase the effectiveness of modern antidepressant therapy (with second-generation drugs) in the elderly has been shown, presumably by potentiating the therapeutic effect of antidepressants or by improving their tolerability, which makes it possible to safely use higher doses of antidepressants in the elderly and senile patients.

scholarly journals Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morteza Heidarzadeh ◽  
Yasemin Gürsoy-Özdemir ◽  
Mehmet Kaya ◽  
Aysan Eslami Abriz ◽  
Amir Zarebkohan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Large Population ◽  
Drug Carriers ◽  
The Elderly ◽  
Brain Parenchyma ◽  
Main Question ◽  
Inflammatory Conditions ◽  
Degenerative Disorders ◽  
Delivery Strategies ◽  
The Brain

AbstractNowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50–100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.

Gut Microbiota and Alzheimer’s Disease: Experimental Evidence and Clinical Reality

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarama Saha ◽  
Sukhpal Singh ◽  
Suvarna Prasad ◽  
Amit Mittal ◽  
Anil Kumar Sharma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
The Elderly ◽  
The Impact ◽  
The Brain

: Alzheimer’s disease (AD) is characterized by progressive death of neuronal cells in the regions of the brain concerned with memory and cognition, and is the major cause of dementia in the elderly population. Various molecular mechanisms, metabolic risk factors and environmental triggers contributing to the genesis and progression of AD are under intense investigations. The present review has dealt with the impact of a highly discussed topic of gut microbiota affecting the neurodegeneration in the AD brain. A detailed description of the composition of gut bacterial flora and its interaction with the host has been presented, followed by an analysis of key concepts of bi- directional communication between gut microbiota and the brain. The substantial experimental evidence of gut microbiota affecting the neurodegenerative process in experimental AD models has been described next in this review, and finally, the limitations of such experimental studies vis-a- vis the actual disease and the paucity of clinical data on this topic have also been mentioned.

scholarly journals Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Almudena Fuster-Matanzo ◽  
María Llorens-Martín ◽  
Félix Hernández ◽  
Jesús Avila
Keyword(s):  
Immune Response ◽  
Alzheimer Disease ◽  
Adult Neurogenesis ◽  
The Elderly ◽  
Therapeutic Approaches ◽  
Common Cause ◽  
The Central Nervous System ◽  
Chronic Activation ◽  
The Brain

Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field.

Biocontrol laser therapy of kognitive violations in genesis in the elderly

2014 ◽  
Vol 20 (29) ◽  
pp. 8-13
Author(s):  
Бакузова ◽  
Diana Bakuzova ◽  
Загускин ◽  
Sergey Zaguskin
Keyword(s):  
Circadian Rhythms ◽  
Laser Therapy ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Memory Assessment ◽  
Steady Improvement ◽  
The Brain ◽  
Vegetative Status

When cognitive disorders in Genesis in the elderly found violation of the hierarchy of rhythms R-R intervals ECG, with an increase in the amplitude and period of the surplus fluctuations, index Baevsky, reduced performance fractal and dispersion. Sustainable sympaticotonia confirmed the dominance of the lower individual minutes, Kerdo and scaterogrammen. Application of biocontrol laser therapy with irradiation of the frontal, temporal and subnormality zones of the brain leading to reduced sympaticotonia, normalize the rhythms of vegetative status, recovery circadian rhythms pulse and R-R intervals ECG. Test memory assessment in all patients shows steady improvement.

scholarly journals Glycosphingolipids and neuroinflammation in Parkinson’s disease

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Karim Belarbi ◽  
Elodie Cuvelier ◽  
Marie-Amandine Bonte ◽  
Mazarine Desplanque ◽  
Bernard Gressier ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Inflammasome Activation ◽  
Nigrostriatal Pathway ◽  
Neurodegenerative Process ◽  
And Function ◽  
The Brain

Abstract Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of neuronal inclusions known as Lewy bodies. Chronic neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. Glycosphingolipids are a well-defined subclass of lipids that regulate crucial aspects of the brain function and recently emerged as potent regulators of the inflammatory process. Deregulation in glycosphingolipid metabolism has been reported in Parkinson’s disease. However, the interrelationship between glycosphingolipids and neuroinflammation in Parkinson’s disease is not well known. This review provides a thorough overview of the links between glycosphingolipid metabolism and immune-mediated mechanisms involved in neuroinflammation in Parkinson’s disease. After a brief presentation of the metabolism and function of glycosphingolipids in the brain, it summarizes the evidences supporting that glycosphingolipids (i.e. glucosylceramides or specific gangliosides) are deregulated in Parkinson’s disease. Then, the implications of these deregulations for neuroinflammation, based on data from human inherited lysosomal glycosphingolipid storage disorders and gene-engineered animal studies are outlined. Finally, the key molecular mechanisms by which glycosphingolipids could control neuroinflammation in Parkinson’s disease are highlighted. These include inflammasome activation and secretion of pro-inflammatory cytokines, altered calcium homeostasis, changes in the blood-brain barrier permeability, recruitment of peripheral immune cells or production of autoantibodies.

scholarly journals Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain

2020 ◽  
Vol 60 (1) ◽  
pp. 437-456
Author(s):  
Anne Joutel
Keyword(s):  
Critical Appraisal ◽  
Autosomal Dominant ◽  
Vascular Risk Factor ◽  
The Elderly ◽  
Small Vessel ◽  
Therapeutic Approaches ◽  
Intracerebral Hemorrhages ◽  
Heavy Burden ◽  
The Impact ◽  
The Brain

Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor–related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.

scholarly journals The Role of Monocytes Cellular and Molecular Mechanisms in the Development of Systemic Immune Inflammation. Part 1

Psychiatry ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 76-85
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Cognitive Disorders ◽  
Research Data ◽  
Vascular Endothelial ◽  
Platelet Aggregates ◽  
Immune Inflammation ◽  
The Brain

Introduction: the important role of monocytes /macrophages, as well as cytokines produced by them was determined in the pathogenesis of mental disorders, as a macrophage-T-lymphocyte theory of bipolar disorder, schizophrenia and depression. According to this theory, there is an increase in the number of active circulating monocytes, macrophages and T-cells in patients with mental disorders. These cells migrate to the CNS as a result of the blood-brain barrier breach, destabilize the brain and lead to worsening of mental disorders.The aim of work: to review research data on the role of proinflammator monocytes in the development of immune inflammation in the pathogenesis of a number of systemic diseases and to examine the molecular mechanisms mediating the interaction of proinflammatory monocytes with other cells involved in immune inflammation.Material and methods: keywords “proinflammatory monocyte CD16+”, “cytokines”, “molecules of cell adhesion”, “monocyte-platelet aggregates”, “microglia”, “psychiatriс disorders”, are used to search for data published over the past 20 years in domestic and foreign studies in PubMed and e-Library.Conclusion: in the first part of the review, the research data concerning the studies of the functional characteristics of a monocytes subpopulation that express on their surface an increased level of CD16 receptors when activated were analyzed. Most of researchers associate the proinflammatory functions of monocytes with this subpopulation. Molecular mechanisms of monocytes activation, which include increased secretion of CD16 receptors, cytokines, chemokines and receptors for them involved in their interaction with vascular endothelial cells, with neurons in the CNS and also with platelets in the development of systemic inflammation, are considered. Analysis of these mechanisms allows us to better understand the immune aspects of inflammation in the brain mediated by the interaction of CD16+ monocytes with neuronal cells, which results in cognitive disorders in patients with mental disorders, as well as to identify related new approaches to the treatment of cognitive decline in these patients. Studies of the monocyte unit of immunity in patients with mental disorders will be covered in the second part of the review.

scholarly journals Age-linked suppression of lipoxin A4 mediates cognitive deficits in mice and humans

2021 ◽  
Author(s):  
Fabrício A. Pamplona ◽  
Gabriela Vitória ◽  
Felipe C. Ribeiro ◽  
Carolina A. Moraes ◽  
Pitia F. Ledur ◽  
...  
Keyword(s):  
Memory Performance ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Lipid Mediator ◽  
Lipoxin A4 ◽  
Age Related ◽  
Learning Impairment ◽  
The Brain

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associates with memory performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-β. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.

scholarly journals Molecular Mechanisms of Cancer-Induced Sleep Disruption

2019 ◽  
Author(s):  
William H. Walker II ◽  
Jeremy C. Borniger
Keyword(s):  
Molecular Mechanisms ◽  
Systemic Disease ◽  
Sleep Disruption ◽  
Poor Sleep ◽  
Therapeutic Approaches ◽  
Treatment Regimens ◽  
Patients With Cancer ◽  
And Behavior ◽  
The Brain

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Lessons From the Neural Bases of Speech and Voice

2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow
Keyword(s):  
Brain Networks ◽  
Neural Substrates ◽  
Voice Behavior ◽  
Therapeutic Approaches ◽  
Neural Bases ◽  
Sound Foundation ◽  
The Brain ◽  
Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

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