Neurodegenerative Diseases

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was ident...

Alzheimer’s disease (AD) is the major cause of dementia in the elderly. The biochemical changes that precede AD may be present up to 20 years before the clinical manifestation of the disease. The translational development of AD biomarkers may be theoretically achieved via two different strategies: the first strategy can be defined as ‘knowledge-based’ (deductive method), while the second one

Background: A subset of patients with schizophrenia, defined on the basis of longitudinal deficits in self-care, may show a classic (“Kraepelinian”) degenerative course. An independent validator of the phenomenologically defined Kraepelinian subtype might be provided by a structural indicator of possible brain degeneration: ventricular size as measured by computed tomography (CT).Methods: To examine whether Kraepelinian patients would show a differential increase in ventricular size over time, two CT scans were conducted at intervals separated by >4 years, an average of 5 years. Fifty-three male patients with DSM-III-R diagnoses of chronic schizophrenia were subdivided into Kraepelinian (n = 22; mean age = 42 ± 8.6 years) and non-Kraepelinian (n = 31; mean age = 38 ± 12.2 years) subgroups. Kraepelinian patients were defined on the basis of longitudinal criteria: >5 years of complete dependence on others for life necessities and care, lack of employment, and sustained symptomatology. Thirteen normal elderly volunteers (mean age = 60 ± 17.8) were also scanned at 4-year intervals. CT measurements were made by raters without knowledge of subgroup membership. A semiautomated computer program was used to trace the anterior horn, lateral ventricles, and temporal horns for each slice level on which they were clearly seen.Results: The ventricles showed a bilateral increase in size over the 4-year interval in the Kraepelinian subgroup, more marked in the left hemisphere than the right. By contrast, neither the non-Kraepelinian subgroup nor the normal volunteers showed significant CT changes from scan 1 to scan 2.Conclusions: Thus, the longitudinal dysfunctions in self-care that characterize the Kraepelinian patients were associated with an independent indicator of brain abnormality.

Background/Aims: Neurodegenerative disorders (ND) have a major impact on quality of life (QoL) and place a substantial burden on patients, their families and carers; they are the second leading cause of disability. The objective of this study was to examine QoL in persons ...

Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as p...

Ascorbate (vitamin C) is a vital antioxidant molecule in the brain. However, it also has a number of other important functions, participating as a co-factor in several enzyme reactions including catecholamine synthesis, collagen production and regulation of HIF-1α. Ascorbate is transported into the brain and neurons via the Sodium-dependent Vitamin C Transporter-2 (SVCT2), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters of the GLUT family. Once in cells, it is rapidly reduced to ascorbate. The highest concentrations of ascorbate in the body are found in the brain and neuroendocrine tissues such as adrenal, although the brain is the most difficult organ to deplete of ascorbate. Combined with regional asymmetry in ascorbate distribution within different brain areas, these facts suggest an important role for ascorbate in the brain. Ascorbate is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic and GABAergic transmission and related behaviors. Neurodegenerative diseases typically involve high levels of oxidative stress and thus ascorbate has been posited to have potential therapeutic roles against ischemic stroke, Alzheimer's disease, Parkinson's disease and Huntingdon's disease.

A B S T R A C T Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones. The cRNA hybridization analysis from mock-and TMEV-infected cells showed an upregulation of a potassium transport channel coding sequence. We validated this mRNA increase by RT-PCR and quantitative PCR using Kir 4.1 specific primers. Western blotting experiments confirmed the upregulation of Kir 4.1, and alignment between sequences provided the demonstration that the over-expressed gene encodes for a Kir family member. Flow cytometry showed that the Kir 4.1 protein is located mainly in the cell membrane in mock and TMEV-infected astrocytes. Our results demonstrate an increase in K + inward current in TMEV-infected glial cells, this increment may reduce the neuronal depolarization, contributing to cell resilience mechanisms.

Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain...

Spinal muscular atrophy (SMA) is a severe autosomal recessive disease caused by a genetic defect in the survival motor neuron 1 (SMN1) gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. Depletion of the SMN protein causes muscle weakness and progressive loss of movement in SMA patients. The field of gene therapy has made major advances over the past decade, and gene delivery to the central nervous system (CNS) by in vivo or ex vivo techniques is a rapidly emerging field in neuroscience. Despite Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis being among the most common neurodegenerative diseases in humans and attractive targets for treatment development, their multifactorial origin and complicated genetics make them less amenable to gene therapy. Monogenic disorders resulting from modifications in a single gene, such as SMA, prove more favorable and have been at the fore of this evolution of potential gene therapies, and results to date have been promising at least. With the estimated number of monogenic diseases standing in the thousands, elucidating a therapeutic target for one could have major implications for many more. Recent progress has brought about the commercialization of the first gene therapies for diseases, such as pancreatitis in the form of Glybera, with the potential for other monogenic disease therapies to follow suit. While much research has been carried out, there are many limiting factors that can halt or impede translation of therapies from the bench to the clinic. This review will look at both recent advances and encountered impediments in terms of SMA and endeavor to highlight the promising results that may be applicable to various associated diseases and also discuss the potential to overcome present limitations.

—Mathematical and computational modellings are the necessary tools for reviewing, analysing, and predicting processes and events in the wide spectrum range of scientific fields. Therefore, in a field as rapidly developing as neuroscience, the combination of these two modellings can have a significant role in helping to guide the direction the field takes. The paper combined mathematical and computational modelling to prove a weakness in a very precious model in neuroscience. This paper is intended to analyse all-or-none principle in Hodgkin-Huxley mathematical model. By implementation the computational model of Hodgkin-Huxley model and applying the concept of all-or-none principle, an investigation on this mathematical model has been performed. The results clearly showed that the mathematical model of Hodgkin-Huxley does not observe this fundamental law in neurophysiology to generating action potentials. This study shows that further mathematical studies on the Hodgkin-Huxley model are needed in order to create a model without this weakness.

Aim

As the population ages, the problem of dementia increases and affects a growing number of people. People with mental illness are known to be stigmatised and this has been the subject of numerous studies. There have been contradictory studies assessing the stigma attached to dementia, and the majority focus on stigma at a social level and the public perception of people with dementia. There have been a number of projects that included a study group of people with dementia. However, to date, this topic has not been discussed in Poland. Hence, the aim of this paper is to carry out a literature review addressing this issue.

Perspective

The problem of stigma attached to dementia is particularly significant as it affects not only the subject, but also their family, friends and health professionals. As people with dementia develop cognitive impairment and lose their independence, stigmatisation leads to their social isolation, despite their need for care. Stigma has emotional, behavioural and social implications, including diminished self-esteem, a feeling of anxiety and the development of a sense of shame and a fear of the judgement of others. Family members also deal with the stigma, which manifests itself as embarrassment and anxiety and causes their circle of friends and acquaintances to decrease. Current studies show that professionals can also play a negative role in the process of labelling and stigmatisation of patients.

Conclusion

Stigma is a serious and common problem in dementia. It seems necessary to target this issue in research and social discourse.

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastroin-testinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecul...

Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions. We searched MEDLINE via PubMed, 'Banque de Données de Santé Publique' and the database of the 'Institut d'Epidemiologie Neurologique et de Neurologie Tropicale' from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated. In all 144 publications reporting on dementia (n = 49 publications, mainly Alzheimer disease), Parkinsonis...

Abstrak Meningkatnya usia harapan hidup penduduk di Indonesia, menyebabkan jumlah penduduk usia lanjut terus meningkat dari tahun ke tahun. Salah satu permasalahan yang sering timbul pada lansia salah satunya berupa demensia atau yang sering kita sebut dengan pikun. Demensia atau pikun adalah suatu sindroma neurodegeneratif yang timbul karena adanya kelainan yang bersifat kronis dan progesifitas disertai dengan gangguan fungsi luhur multiple seperti berhitung, kapasitas belajar, bahasa, dan mengambil keputusan sehingga mempengaruhi aktivitas sosial dan aktivitas sehari-hari. Demensia bukanlah suatu penyakit yang spesifik, melainkan suatu gejala yang bisa disebabkan oleh berbagai kelainan yang mempengaruhi otak. Angka kejadian demensia di dunia pada tahun 2019 diperkirakan terdapat 47,47 juta, diperkirakan akan meningkat menjadi 75,63 juta pada tahun 2030 dan 135,46 juta pada tahun 2050. Jumlah lansia yang mengalami demensia di dunia sebesar 30 juta jiwa dan di Indonesia sebesar 15 % dari jumlah lansianya mengalami demensia. Demensia merupakan penyebab kematian ke-4 pada lansia setelah penyakit jantung, kanker dan stroke. Kasus demensia yang terdiagnosis sering tidak mendapat penatalaksanaan yang memadai sehingga pasien tidak mencapai kualitas hidup optimal. Maka dari itu, sebaiknya kita mengenali lebih awal apa itu demensia, faktor resiko demensia, gejala-gejala demensia, dan cara pencegahannya sehingga kita dapat menunda bahkan mencegah kepikunan. Abstract The increasing life expectancy of the population in Indonesia, causes the number of elderly population continues to increase from year to year. One of the problems that often arises in the elderly one of which is dementia or what we often call senile. Dementia or senile dementia is a neurodegenerative syndrome that arises due to chronic and progressive disorders accompanied by multiple sublime functions such as arithmetic, learning capacity, language, and decision making that affect social activities and daily activities. Dementia is not a specific disease, but rather a symptom that can be caused by various disorders that affect the brain. The incidence of dementia in the world in 2019 is estimated to be 47.47 million, is expected to increase to 75.63 million in 2030 and 135.46 million in 2050. Dementia is the 4th leading cause of death in the elderly after heart disease, cancer and stroke. The number of elderly people with dementia in the world is 30 million people and in Indonesia 15% of the total population has dementia. Cases of diagnosed dementia often do not get adequate management so that patients do not achieve optimal quality of life. Therefore, we should recognize early what is dementia, risk factors of dementia, symptoms of dementia, and how to prevent it so that we can delay or even prevent senility.