scholarly journals A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 34
Author(s):  
Kohei Segawa ◽  
Yukari Blumenthal ◽  
Yuki Yamawaki ◽  
Gen Ohtsuki
Keyword(s):  
Neurodegenerative Diseases ◽  
Lymphatic System ◽  
Psychiatric Symptoms ◽  
Neurological Diseases ◽  
Immune Surveillance ◽  
Brain Network ◽  
Cellular Mechanisms ◽  
Postmortem Brains ◽  
New Interpretation ◽  
The Brain

The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

scholarly journals Cerebral sterile inflammation in neurodegenerative diseases

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Kento Otani ◽  
Takashi Shichita
Keyword(s):  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Sterile Inflammation ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Abnormal Accumulation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractTherapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

scholarly journals The Use of Proteomics in Biomarker Discovery in Neurodegenerative Diseases

2005 ◽  
Vol 21 (2) ◽  
pp. 81-92 ◽  
Author(s):  
Pia Davidsson ◽  
Magnus Sjögren
Keyword(s):  
Neurodegenerative Diseases ◽  
Biomarker Discovery ◽  
Neurological Diseases ◽  
Synaptic Proteins ◽  
Clinical Proteomics ◽  
Protein Patterns ◽  
Differential Protein ◽  
Csf Proteins ◽  
New Biomarkers ◽  
The Brain

Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein,β-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of bothβ-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-β-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.

scholarly journals Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Musbau Adewumi Akanji ◽  
Damilare Emmanuel Rotimi ◽  
Tobiloba Christiana Elebiyo ◽  
Oluwakemi Josephine Awakan ◽  
Oluyomi Stephen Adeyemi
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Redox Homeostasis ◽  
Reactive Species ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Cellular Redox ◽  
Redox Imbalance ◽  
Cellular Processes ◽  
The Brain

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

scholarly journals Brain lymphatic drainage system – visualization opportunities and current state of the art

2020 ◽  
Vol 9 (3) ◽  
pp. 81-89
Author(s):  
G. S. Yankova ◽  
O. B. Bogomyakova
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Lymphatic Drainage ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.

scholarly journals Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7710
Author(s):  
Ying-Chieh Wu ◽  
Tuuli-Maria Sonninen ◽  
Sanni Peltonen ◽  
Jari Koistinaho ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Induced Pluripotent Stem Cell ◽  
Brain Barrier ◽  
Blood Brain ◽  
Induced Pluripotent ◽  
The Brain

The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.

Aging of Brain Related with Mitochondrial Dysfunctions

2020 ◽  
Vol 21 ◽  
Author(s):  
Vipin Dhote ◽  
Prem Samundre ◽  
Aditya Ganeshpurkar ◽  
Aman Upaganlawar
Keyword(s):  
Neurodegenerative Diseases ◽  
Psychiatric Symptoms ◽  
Neuronal Damage ◽  
The Elderly ◽  
Environmental Chemicals ◽  
Aging Brain ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Key Issues ◽  
The Brain

Abstract:: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

scholarly journals Amygdala: Neuroanatomical and Morphophysiological Features in Terms of Neurological and Neurodegenerative Diseases

2020 ◽  
Vol 10 (8) ◽  
pp. 502
Author(s):  
Vladimir N. Nikolenko ◽  
Marine V. Oganesyan ◽  
Negoriya A. Rizaeva ◽  
Valentina A. Kudryashova ◽  
Arina T. Nikitina ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Chronic Traumatic Encephalopathy ◽  
Neurological Diseases ◽  
Hippocampal Sclerosis ◽  
Degenerative Diseases ◽  
Behavioral Synthesis ◽  
Level Of Activity ◽  
Input Signals ◽  
The Subject ◽  
The Brain

The amygdala is one of the most discussed structures of the brain. Correlations between its level of activity, size, biochemical organization, and various pathologies are the subject of many studies, and can serve as a marker of existing or future disease. It is hypothesized that the amygdala is not just a structural unit, but includes many other regions in the brain. In this review, we present the updated neuroanatomical and physiological aspects of the amygdala, discussing its involvement in neurodegenerative and neurological diseases. The amygdala plays an important role in the processing of input signals and behavioral synthesis. Lesions in the amygdala have been shown to cause neurological disfunction of ranging severity. Abnormality in the amygdala leads to conditions such as depression, anxiety, autism, and also promotes biochemical and physiological imbalance. The amygdala collects pathological proteins, and this fact can be considered to play a big role in the progression and diagnosis of many degenerative diseases, such as Alzheimer’s disease, chronic traumatic encephalopathy, Lewy body diseases, and hippocampal sclerosis. The amygdala has shown to play a crucial role as a central communication system in the brain, therefore understanding its neuroanatomical and physiological features can open a channel for targeted therapy of neurodegenerative diseases.

The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Galina Yankova ◽  
Olga Bogomyakova ◽  
Andrey Tulupov
Keyword(s):  
Neurodegenerative Diseases ◽  
Brain Injuries ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Waste Products ◽  
Glymphatic System ◽  
System A ◽  
Age Related ◽  
The Brain

Abstract The glymphatic system and meningeal lymphatics have recently been characterized. Glymphatic system is a glia-dependent system of perivascular channels, and it plays an important role in the removal of interstitial metabolic waste products. The meningeal lymphatics may be a key drainage route for cerebrospinal fluid into the peripheral blood, may contribute to inflammatory reaction and central nervous system (CNS) immune surveillance. Breakdowns and dysfunction of the glymphatic system and meningeal lymphatics play a crucial role in age-related brain changes, the pathogenesis of neurovascular and neurodegenerative diseases, as well as in brain injuries and tumors. This review discusses the relationship recently characterized meningeal lymphatic vessels with the glymphatic system, which provides perfusion of the CNS with cerebrospinal and interstitial fluids. The review also presents the results of human studies concerning both the presence of meningeal lymphatics and the glymphatic system. A new understanding of how aging, medications, sleep and wake cycles, genetic predisposition, and even body posture affect the brain drainage system has not only changed the idea of brain fluid circulation but has also contributed to an understanding of the pathology and mechanisms of neurodegenerative diseases.

scholarly journals Curcumin Ameliorates the Cd-Induced Anxiety-like Behavior in Mice by Regulating Oxidative Stress and Neuro-Inflammatory Proteins in the Prefrontal Cortex Region of the Brain

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1710
Author(s):  
Dhondup Namgyal ◽  
Sher Ali ◽  
Muhammad Delwar Hussain ◽  
Mohsin Kazi ◽  
Ajaz Ahmad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Working Memory ◽  
Prefrontal Cortex ◽  
Neurodegenerative Diseases ◽  
Spatial Working Memory ◽  
Cellular Mechanisms ◽  
Behavioral Impairment ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

Age-related neurodegenerative diseases and vascular dementia are major challenges to the modern health care system. Most neurodegenerative diseases are associated with impaired spatial working memory and anxiety-like behavior. Thus, it is important to understand the underlying cellular mechanisms of neurodegenerative diseases in different regions of the brain to develop an effective therapeutic approach. In our previous research paper, we have reported the ameliorative effect of curcumin in Cd-induced hippocampal neurodegeneration. However, recently many researchers had reported the important role of the prefrontal cortex in higher cognitive functions. Therefore, to look into the cellular mechanism of curcumin protection against Cd-induced prefrontal cortex neurotoxicity, we investigated spatial working memory, anxiety-like behavior and analyzed prefrontal cortex inflammatory markers (IL-6, IL-10, and TNFα), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant MDA level. Further, we conducted histological studies of the prefrontal cortex in Swiss albino mice exposed to cadmium (2.5 mg/kg). We observed that curcumin treatment improved the spatial working memory and anxiety-like behavior of mice through reduction of prefrontal cortex neuroinflammation and oxidative stress as well as increasing the number of viable prefrontal cortex neuronal cells. Our result suggests that environmental heavy metal cadmium can induce behavioral impairment in mice through prefrontal cortex cellular inflammation and oxidative stress. We found that curcumin has a potential therapeutic property to mitigate these behavioral and biochemical impairments induced by cadmium.

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