Neuroinflammation in Parkinson's Disease: From Gene to Clinic: A Systematic Review.

Parkinson's disease is a neurodegenerative disease whose progression and clinical characteristics have a close bidirectional and multilevel relationship with the process of neuroinflammation. In this context, it is necessary to understand the mechanisms involved in this neuroinflammation-PD link. This systematic search was, hereby, conducted with a focus on the four levels where alterations associated with neuroinflammation in PD have been described (genetic, cellular, histopathological and clinical-behavioral) by consulting the PubMed, Google Scholar, Scielo and Redalyc search engines, including clinical studies, review articles, book chapters and case studies. Initially, 585,772 articles were included, and, after applying the inclusion and exclusion criteria, 84 articles were obtained that contained information about the multilevel association of neuroinflammation with alterations in gene, molecular, cellular, tissue and neuroanatomical expression as well as clinical-behavioral manifestations in PD.

The Role of Astrocytes and Alpha-Synuclein in Parkinson's Disease: A Review.

The search for new therapies to reduce symptoms and find a cure for Parkinson's disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson's disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease.

Alterations of mRNAs and Non-coding RNAs Associated with Neuroinflammation in Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative pathology whose pathognomonic hallmarks are increased generation of ß-amyloid (Aß) peptide, production of hyperphosphorylated (pTau), and neuroinflammation. The last is an alteration closely related to the progression of AD and although it is present in multiple neurodegenerative diseases, the pathophysiological events that characterize neuroinflammatory processes vary depending on the disease. In this article, we focus on mRNA and non-coding RNA alterations as part of the pathophysiological events characteristic of neuroinflammation in AD and the influence of these alterations on the course of the disease through interaction with multiple RNAs related to the generation of Aß, pTau, and neuroinflammation itself.

Alzheimer's Disease: Cellular and Pharmacological Aspects.

Alzheimer's disease was described more than 100 years ago and despite the fact that several molecules are being tested for its treatment, which are in phase III trials, the disease continues to progress. The main problem is that these molecules function properly in healthy neurons, while neuronal pathology includes plasma membrane disruption, malfunction of various organelles, and hyperphosphorylation of Tau and amyloid plaques. The main objective of this article is the discussion of a neuronal restoration therapy, where molecules designed for the treatment of Alzheimer's disease would probably be more effective, and the quality of life of people would be better.

Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish.

The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

The Anatomy, Histology, and Function of the Major Pelvic Ganglion.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

Potential drugs for the treatment of Alzheimer's disease.

It is well known that amyloid precursor protein (APP), the enzyme ß-secretase 1 (BACE1), cyclooxygenase 2 (COX-2), nicastrin (NCT), and hyperphosphorylated tau protein (p-tau) are closely related to the development of Alzheimer's disease (AD). In addition, recent evidence shows that neuroinflammation also contributes to the pathogenesis of AD. Although the mechanism is not clearly known, such inflammation could alter the activity of the aforementioned molecules. Therefore, the use of anti-inflammatory agents could slow the progression of the disease. Nimesulide, resveratrol, and citalopram are three anti-inflammatory agents that could contribute to a decrease in neuroinflammation and consequently to a decrease in the overexpression of APP, BACE1, COX-2, NCT, and p-Tau, as they possess anti-inflammatory effects that could regulate the expression of APP, BACE1, COX-2, NCT, and p-Tau of potent pro-inflammatory markers indirectly involved in the expression of APP, BACE1, NCT, COX-2, and p-Tau; therefore, their use could be beneficial as preventive treatment as well as in the early stages of AD.

Olfactory Dysfunction in Parkinson's Disease, Its Functional and Neuroanatomical Correlates.

Parkinson's disease (PD) is known for its motor alterations, but the importance of non-motor symptoms (NMSs), such as olfactory dysfunction (OD), is increasingly recognized. OD may manifest during the prodromal period of the disease, even before motor symptoms appear. Therefore, it is suggested that this symptom could be considered a marker of PD. This article briefly describes PD, the evolution of the knowledge about OD in PD, the prevalence of this NMS and its role in diagnosis and as a marker of PD progression, the assessment of olfaction in patients with PD, the role of α-synuclein and its aggregates in the pathophysiology of PD, and then describes some functional, morphological, and histological alterations observed in different structures related to the olfactory system, such as the olfactory epithelium, olfactory bulb, anterior olfactory nucleus, olfactory tract, piriform cortex, hippocampus, orbitofrontal cortex, and amygdala. In addition, considering the growing evidence that suggests that the cerebellum is also involved in the olfactory system, it has also been included in this work. Comprehending the existing functional and neuroanatomical alterations in PD could be relevant for a better understanding of the mechanisms behind OD in patients with this neurodegenerative disorder.

Involvement of the PRL-PAK1 Pathway in Cancer Cell Migration.

Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.

Atlas of Nervous System Vascular Malformations: A Systematic Review.

Vascular malformations are frequent in the head and neck region, affecting the nervous system. The wide range of therapeutic approaches demand the correct anatomical, morphological, and functional characterization of these lesions supported by imaging. Using a systematic search protocol in PubMed, Google Scholar, Ebsco, Redalyc, and SciELO, the authors extracted clinical studies, review articles, book chapters, and case reports that provided information about vascular cerebral malformations, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 385,614 articles were grouped; using the inclusion and exclusion criteria, three of the authors independently selected 51 articles about five vascular cerebral malformations: venous malformation, brain capillary telangiectasia, brain cavernous angiomas, arteriovenous malformation, and leptomeningeal angiomatosis as part of Sturge-Weber syndrome. We described the next topics-"definition", "etiology", "pathophysiology", and "treatment"-with a focus on the relationship with the imaging approach. We concluded that the correct anatomical, morphological, and functional characterization of cerebral vascular malformations by means of various imaging studies is highly relevant in determining the therapeutic approach, and that new lines of therapeutic approaches continue to depend on the imaging evaluation of these lesions.

Current Opinion on the Use of c-Fos in Neuroscience.

For years, the biochemical processes that are triggered by harmful and non-harmful stimuli at the central nervous system level have been extensively studied by the scientific community through numerous techniques and animal models. For example, one of these techniques is the use of immediate expression genes, which is a useful, accessible, and reliable method for observing and quantifying cell activation. It has been shown that both the c-fos gene and its protein c-Fos have rapid activation after stimulus, with the length of time that they remain active depending on the type of stimulus and the activation time depending on the stimulus and the structure studied. Fos requires the participation of other genes (such as c-jun) for its expression (during hetero-dimer forming). c-Fos dimerizes with c-Jun protein to form factor AP-1, which promotes the transcription of various genes. The production and removal of c-Fos is part of cellular homeostasis, but its overexpression results in increased cell proliferation. Although Fos has been used as a marker of cellular activity since the 1990s, which molecular mechanism participates in the regulation of the expression of this protein is still unknown because the gene and the protein are not specific to neurons or glial cells. For these reasons, this work has the objective of gathering information about this protein and its use in neuroscience.

Amantadine in the prevention of clinical symptoms caused by SARS-CoV-2.

BACKGROUND: Amantadine is a drug that can help in the prevention of SARS-CoV-2 symptomatology, as has been demonstrated in observational clinical studies. METHODS: We searched in the PubMed database Clinical Studies of coronavirus-infected patients who have been treated with amantadine in a preventive manner as well as patients with Parkinson's disease. RESULTS: Four clinical studies were found in which relatives of patients with COVID-19 had been prescribed the use of amantadine in a preventive manner to avoid the symptoms caused by the coronavirus. CONCLUSION: Amantadine is a drug that can be prescribed as a prophylactic that prevents symptomatology caused by SARS-CoV-2 coronavirus.

Amantadine Treatment for People with COVID-19.

SARS-Cov-2, whose symptoms include difficulty swallowing, coughing, diarrhea, and breathing failure, has caused the loss of many lives around the world. In the absence of a vaccine or medication to help prevent or decrease the effects of the disease, we suggest that amantadine may reduce the effects of COVID-19.

Observational study of people infected with SARS-Cov-2, treated with amantadine.

BACKGROUND: We conducted an observational study of 15 patients from a Southeastern area of Mexico with symptoms compatible with SARS-Cov-2, which were treated with the antiviral amantadine. METHODOLOGY: In this study, data were collected from 15 individuals with clinical symptoms of COVID-19 infection, which were treated on an ambulatory basis with 100 mg of amantadine for a period of 14 days. RESULTS: This drug demonstrated its effectiveness, as patients recovered successfully with this treatment without the necessity of attending a hospital to use mechanical ventilation. All patients developed IgG antibodies to SARS-Cov-2. CONCLUSION: Amantadine can be used as a viable and cost-effective alternative for treating people with severe acute respiratory syndrome (SARS-Cov-2) on an ambulatory basis, while the vaccine is not available.

Razor scrape assay, an alternative variation to wound and healing assays.

Cell migration is the process by which cells move through tissues, and it is crucial to carry out a wide variety of physiological and pathological processes. The study methods to evaluate cell migration are very useful tools for biomedical research. Among these methods, the wound and healing assay is one of the simplest, most economical and is widely used in research. However, one of its disadvantages is that the width and shape of the wound can vary among experimental samples since the scraping is carried out manually, representing a difficult variable to control. In the present article a variant of the razor scrape assay is addressed, which eliminates this variation in the width of the wound, thus facilitating the measurement and comparison using the total area of cell migration.•A method that can be carried out under standard culture conditions.•Avoids the disadvantage of variation in width and shape of the wound.•It constitutes a simple, cheap option and multiple advantages over the traditional method.

Rehabilitating a brain with Alzheimer's: a proposal.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, originating sporadically in the population aged over 65 years, and advanced age is the principal risk factor leading to AD development. In spite of the large amount of research going on around the globe and all the information now available about AD, there is still no origin or triggering process known so far. Drugs approved for the treatment of AD include tacrine, donepezil, rivastigmine, galantamine, and memantine. These may delay or slow down the degenerative process for a while, but they can neither stop nor reverse its progression. Because that this might be due to a lack of effect of these drugs on degenerating neurons, even when they are able to potentiate the brain in nondegenerative conditions, we propose here an alternative therapy consisting of initial repair of neuronal membranes followed by conventional drug therapies. The rehabilitation of neurons in a degeneration process would enable the drugs to act more effectively on them and improve the effects of treatment in AD patients.

[Alzheimer's disease: immunity and diagnosis]. / Enfermedad de Alzheimer: inmunidad y diagnostico.

INTRODUCTION: Alzheimer's disease is a slowly progressing neurodegenerative disease that presents cognitive impairment, progressive loss of memory and conduct disorders. The main risk factor is advanced age. There is currently no cure for this disease and, consequently, important efforts have been made to describe readily accessible methods that allow it to be diagnosed earlier, as well as more effective treatments. DEVELOPMENT: A great amount of research focused on the prevention, diagnosis and treatment of Alzheimer's disease is being carried out around the world. In this study we review the main aspects involved in the pathological process of the disease, with emphasis on the changes that generate an immune response and the possible diagnostic markers that have been proposed. CONCLUSIONS: Today, a large body of information on Alzheimer's disease is available. Nevertheless, it is still important to continue with research that allows these patients to improve their quality of life by means of earlier and more accurate diagnoses, as well as more appropriate treatments.