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Cancers Mar 2023While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the... (Review)
Review
BACKGROUND AND AIM
While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM's role in shaping tumoral development.
METHODS
An online literature search was launched on PubMed/Medline and Scopus using the research string "((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))", and a systematic review was conducted in accordance with the PRISMA-P guidelines.
RESULTS
The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns.
CONCLUSIONS
Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.
PubMed: 36980765
DOI: 10.3390/cancers15061879 -
Molecular Neurobiology Oct 2022Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between... (Review)
Review
Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.
Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the "quantal" elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.
Topics: Antipsychotic Agents; Dopamine; Glutamic Acid; Humans; Inflammation; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 35963926
DOI: 10.1007/s12035-022-02976-3 -
CNS Spectrums Jun 2022The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes... (Review)
Review
The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes in mood disorder. We carried out a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed, PsycINFO, and Embase electronic databases for literature related to mood disorders, sleep disturbances, and neurodegenerative/neuroprogressive processes in relation to (1) neuroinflammation, (2) activation of the stress system, (3) oxidative stress, (4) accumulation of neurotoxic proteins, and (5) neuroprotection deficit. Seventy articles were collectively selected and analyzed. Experimental and clinical studies revealed that insomnia, conditions of sleep loss, and altered circadian sleep may favor neurodegeneration and neuroprogression in mood disorders. These sleep disturbances may induce a state of chronic inflammation by enhancing neuroinflammation, both directly and indirectly, via microglia and astrocytes activation. They may act as neurobiological stressors that by over-activating the stress system may negatively influence neural plasticity causing neuronal damage. In addition, sleep disturbances may favor the accumulation of neurotoxic proteins, favor oxidative stress, and a deficit in neuroprotection hence contributing to neurodegeneration and neuroprogression. Targeting sleep disturbances in the clinical practice may hold a neuroprotective value for mood disorders.
Topics: Humans; Mood Disorders; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 33427150
DOI: 10.1017/S1092852921000018 -
Neuroscience and Biobehavioral Reviews Aug 2019Bipolar disorder (BD) is a complex neurobiological disease. It is likely that both neurons and glial cells are affected in BD, yet how these cell types are changed at... (Review)
Review
Bipolar disorder (BD) is a complex neurobiological disease. It is likely that both neurons and glial cells are affected in BD, yet how these cell types are changed at the structural and functional level is still largely unknown. In this review we provide an overview of postmortem studies analyzing structural cellular changes in BD, including the density, number and size of neurons and glia. We categorize the results per cell-type and validate outcome measures per brain region. Despite variations by brain region, outcome measure and methodology, several patterns could be identified. Total neuron, total glia, and cell subtypes astrocyte, microglia and oligodendrocyte presence appears unchanged in the BD brain. Interneuron density may be decreased across various cortical areas, yet findings of interneuron subpopulations show discrepancies. This structural review brings to light issues in validation and replication. Future research should therefore prioritize the validation of existing studies in order to increasingly refine the conceptual models of BD.
Topics: Bipolar Disorder; Brain; Humans; Neuroglia; Neurons
PubMed: 31163205
DOI: 10.1016/j.neubiorev.2019.05.027 -
Biomolecules Feb 2023The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer's disease (AD). It can take place 20-30 years... (Review)
Review
The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer's disease (AD). It can take place 20-30 years before the onset of clinical symptoms. The imbalance between the production and the clearance of Aβ is one of the major causes of AD. Enhancing Aβ clearance at an early stage is an attractive preventive and therapeutic strategy of AD. Direct inhibition of Aβ production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Novel approaches are required to understand and combat Aβ deposition. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. The role of non-neurons in AD has not been fully elucidated. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of Aβ formation and the identification of effective drug targets. AD patient-derived pluripotent stem cells (PSCs) contain complete disease background information and have the potential to differentiate into various types of neurons and non-neurons in vitro, which may bring new insight into the treatment of AD. Here, we systematically review the latest studies on Aβ clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to Aβ plaques, which will be beneficial to explore methods for reconstructing AD disease models using inducible PSCs (iPSCs) through cell differentiation techniques and validating the applications of models in understanding the formation of Aβ plaques. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Neurons; Brain; Astrocytes
PubMed: 36830682
DOI: 10.3390/biom13020313 -
Frontiers in Cellular Neuroscience 2024Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including...
Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including delusions, hallucinations, disorganized speech and behavior, and cognitive impairment. Recent research has suggested that the immune system dysregulation may play a significant role in the pathogenesis of schizophrenia, and glial cells, such as astroglia and microglia known to be involved in neuroinflammation and immune regulation, have emerged as potential players in this process. The aim of this systematic review is to summarize the glial hallmarks of schizophrenia, choosing as cellular candidate the astroglia and microglia, and focusing also on disease-associated psychological (cognitive and emotional) changes. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Scopus, and Web of Science for articles that investigated the differences in astroglia and microglia in patients with schizophrenia, published in the last 5 years. The present systematic review indicates that changes in the density, morphology, and functioning of astroglia and microglia may be involved in the development of schizophrenia. The glial alterations may contribute to the pathogenesis of schizophrenia by dysregulating neurotransmission and immune responses, worsening cognitive capabilities. The complex interplay of astroglial and microglial activation, genetic/epigenetic variations, and cognitive assessments underscores the intricate relationship between biological mechanisms, symptomatology, and cognitive functioning in schizophrenia.
PubMed: 38419655
DOI: 10.3389/fncel.2024.1358450 -
Diagnostics (Basel, Switzerland) Mar 2023Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD is clinical, neuroimaging plays a key role in the evaluation of patients who present symptoms related to neurodegenerative disorders. MRI, DAT-SPECT, and PET with [F]-FDG are routinely used in the diagnosis and focus on the investigation of morphological changes, nigrostriatal degeneration or shifts in glucose metabolism in patients with parkinsonian syndromes. The aim of this study is to review the current PET radiotracers targeting TSPO, a transmembrane protein that is overexpressed by microglia in another pathophysiological process associated with neurodegenerative disorders known as neuroinflammation. To the best of our knowledge, neuroinflammation is present not only in PD but in many other neurodegenerative disorders, including AD, DLB, and MSA, as well as atypical parkinsonian syndromes. Therefore, in this study, specific patterns of microglial activation in PD and the differences in distribution volumes of these radiotracers in patients with PD as compared to other neurodegenerative disorders are reviewed.
PubMed: 36980337
DOI: 10.3390/diagnostics13061029 -
International Journal of Molecular... Apr 2022Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular... (Review)
Review
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 35456984
DOI: 10.3390/ijms23084166 -
Cellular and Molecular Neurobiology Apr 2023Pre-clinical studies place tumor necrosis factor (TNF) as a central player in the inflammatory response after spinal cord injury (SCI), and blocking its production... (Review)
Review
Pre-clinical studies place tumor necrosis factor (TNF) as a central player in the inflammatory response after spinal cord injury (SCI), and blocking its production and/or activity has been proposed as a possible treatment option after SCI. This systematic review provides an overview of the literature on the temporal and cellular expression of TNF after SCI and clarifies the potential for its therapeutic manipulation in SCI. A systematic search was performed in EMBASE (Ovid), MEDLINE (Ovid), and Web of Science (Core Collection). The search terms were the MeSH forms of tumor necrosis factor and spinal cord injury in the different databases, and the last search was performed on February 3, 2021. We found twenty-four articles examining the expression of TNF, with most using a thoracic contusive SCI model in rodents. Two articles described the expression of TNF receptors in the acute phase after SCI. Twenty-one articles described the manipulation of TNF signaling using genetic knock-out, pharmaceutical inhibition, or gain-of-function approaches. Overall, TNF expression increased rapidly after SCI, within the first hours, in resident cells (neurons, astrocytes, oligodendrocytes, and microglia) and again in macrophages in the chronic phase after injury. The review underscores the complexity of TNF's role after SCI and indicates that TNF inhibition is a promising therapeutic option. This review concludes that TNF plays a significant role in the inflammatory response after SCI and suggests that targeting TNF signaling is a feasible therapeutic approach.
Topics: Humans; Tumor Necrosis Factor-alpha; Spinal Cord Injuries; Neurons; Microglia; Macrophages; Spinal Cord
PubMed: 35604578
DOI: 10.1007/s10571-022-01229-0 -
European Psychiatry : the Journal of... Nov 2021Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression,...
BACKGROUND
Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share.
METHODS
We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms.
RESULTS
Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms.
CONCLUSIONS
Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.
Topics: Animals; Anxiety; Catechol O-Methyltransferase; Comorbidity; Depression; Dermatitis, Atopic; Hidradenitis Suppurativa; Humans; Psoriasis; Quality of Life
PubMed: 34819201
DOI: 10.1192/j.eurpsy.2021.2249