Neurodegenerative Disease and the NLRP3 Inflammasome.

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the brain or peripheral nervous system, and generally involve protein aggregation, as well as metabolic abnormalities and immune dysregulation. Although the vast majority of neurodegeneration is idiopathic, there are many known genetic and environmental triggers. In the past decade, research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease or is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, a crucial component of the innate immune system, is usually activated in response to infection or tissue damage. Dysregulation of the NLRP3 inflammasome has been implicated in the progression of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion diseases. This review aims to summarise current literature on the role of the NLRP3 inflammasome in the pathogenesis of neurodegenerative diseases, and recent work investigating NLRP3 inflammasome inhibition as a potential future therapy

Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1

Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability. Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H2S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H2S) in the C73A mutant form of the channel. Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability. These studies highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system

LASTEN SUUSTA -LEHTI NAHKURIN PÄIVÄKODISSA

Projektiopinnäytetyön tilaajana toimi Kokkolan kaupungin varhaiskasvatuksen palvelut. Työelämälähtöinen projektiopinnäytetyö sijoittui Nahkurin päiväkotiin. Opinnäytetyön keskeisiä elementtejä olivat lasten osallisuuden vahvistaminen, mediakasvatus ja tutkiva työote. Projekti pohjautuu Bronfenbrennerin ekologiseen malliin sekä valtakunnalliseen sekä paikalliseen varhaiskasvatussuunnitelmaan. Projektin tavoitteena oli lasten osallisuuden vahvistaminen mediakasvatuksen keinoin, sekä mediakasvatuksen lisääminen ja luovien työmenetelmien hyödyntäminen päiväkodin arjessa. Projektiopinnäytetyön päämääränä oli toteuttaa lehti yhdessä päiväkodin lasten kanssa. Projektiosuus koostui lapsiin tutustumisesta, toiminnallisista interventioista, lehden taittamisesta sekä lehden saattamisesta päiväkodin käyttöön. Projektissa käytettiin työmenetelminä sadutusta, piirtämistä, valokuvausta ja haastattelua. Arvioinnin perusteella voidaan todeta, että päiväkoti on saanut projektin kautta arkeensa uusia näkökulmia lasten osallisuuteen sekä pitkäkestoisen toiminnan järjestämiseen. Palautteiden perusteella voidaan todeta projektin olleen antoisa sekä lapsille että päiväkodin henkilökunnalle.The project was ordered by Day Care and Pre-School Education of Kokkola. The project was initiated from working life. The main elements in the thesis were reinforcing children`s inclusion, media education and researching approach to work. The thesis is based on Bronfenbrenner`s ecological model and also on the nation - wide and local day care education plan and its various orientations. The objective in the project was to reinforce children`s inclusion by using media education and increase the use of media education and creative work methods in the day care center`s daily life. The main goal in the project was to make a news-paper with the children of the day care center. The project part of the thesis consisted of getting to know the children, functional interventions, newspaper layout and getting the finished newspaper to the day care center. Work methods used in the project were storytelling, drawing, photo-graphing and interviewing. The evaluation indicates that the day care center has gotten new perspective into children`s inclusion and organizing long-term functions. According to feedback the project has been rewarding to the children and the personnel of the day care center