A Doença de Parkinson, uma condição neurodegenerativa e progressiva, está relacionada à morte de neurônios localizados na Substância Negra compacta, um dos componentes dos Núcleos da Base. Quando há a morte de neurônios dopaminérgicos nigrais, esta via modulatória é perdida, levando ao desequilíbrio entre as vias direta e indireta, esta última tendo sua atividade aumentada em detrimento da outra. O estriado tem um papel importante no recebimento e filtração de sinais motores corticais e talâmicos e suas maiores populações neuronais são GABAérgicas, demonstrando a importância do neurotransmissor GABA nesta modulação. O estriado recebe projeções dopaminérgicas vindas da Substância Negra compacta e, na falta desta aferentação, surgem os sintomas e sinais da Doença de Parkinson. Nosso objetivo é caracterizar a liberação de GABA nesta estrutura, avaliando os efeitos de outros transmissores e também o papel de alguns sinalizadores intracelulares neste processo. Para isto, empregamos o método de superfusão e liberação de GABA radiomarcado, previamente carregado, em tecido picado in vitro. A lesão nigral é produzida por cirurgia estereotáxica e microinjeção de 6-OHDA no feixe medial prosencefálico (mfb). Diversas drogas foram utilizadas para avaliarmos diferentes passos na liberação do transmissor. Concluímos que a liberação é fortemente dependente de cálcio e segue o modelo de exocitose vesicular, além de a subpopulação neuronal GABAérgica estrital estudada sofrer pouca influência de aferências glutamatérgicas e colinérgicas. No entanto, drogas dopaminérgicas regulam complexamente a liberação de GABA no estriado e ela também é bastante dependente de calmodulina. Conjecturamos se algumas drogas antipsicóticas que agem sobre calmodulina devem seu efeito terapêutico, ou parte dele, a esta ação e se, no modelo de DP de lesão unilateral por 6-OHDA, há comunicação entre os hemisférios lesado e não lesado após o estabelecimento da lesão e processo de rearranjo neuronal / Parkinsons disease, a progressive and neurodegenerative condition, is related to the death of neurons located in Substantia Nigra compacta, a component of Basal Ganglia. When nigral dopaminergic neurons die, this modulatory pathway is lost leading to imbalance between direct and indirect pathways, the latter having its activity increased over the former. Striatum has an essential role in receiving and filtering motor signals from cortex and thalamus and its major neuronal populations are composed by GABAergic neurons, showing how important is GABA in this modulation. Striatum receives dopaminergic projections from Substantia Nigra compacta and in its absence the typical signals and symptoms of the disease arise. We aimed to characterize GABA relase at this structure, assessing the effect of other transmitters as well the role of some intracellular signaling molecules in this process. For that, we employed the superfusion method and release of preloaded radiolabeled GABA from chopped striatal tissue. Nigral injury was produced by stereotaxic surgery and 6-OHDA microinjection at medial forebrain bundle (mfb). Several drugs were used to evaluate different steps in transmitter release. We concluded that the release is strongly calcium-dependent and follows vesicular exocytosis model; in addition the striatal GABAergic subpopulation of neurons studied here undergo little influence of glutamatergic and cholinergic afferents. However, dopaminergic drugs complexly regulate striatal GABA release and it also shows high involvement of calmodulin. We wonder if some antipsychotic drugs that act over calmodulin owe their therapeutical effects, or at least part of it, to this activity and if in 6-OHDA unilateral lesion parkinsonism model there is communication between injuried and healthy hemispheres after the establishment of the injury and neuronal rearrangement process

No description available.

Parkinsons sjukdom är en progressiv kronisk sjukdom som ger en tilltagande försämring av motoriska och kognitiva funktioner. Många personer med Parkinsons sjukdom bor kvar i hemmet och får ett ökat behov av stöd och hjälp. De som tillgodoser detta behov av omvårdnad är ofta närstående som vårdar personen. Detta kan få en påverkan på närståendes hälsa ochlivskvalité. Syftet med denna studie var att beskriva närståendes upplevelser av att leva tillsammans med en person med Parkinsons sjukdom. Tolv vetenskapliga artiklar valdes ut via en litteratursökning och analyserades genom en kvalitativ innehållsanalys med manifest ansats enligt Bengtsson(2016). Analysen resulterade i sex olika slutkategorier; att ha behov av information och kunskap om sjukdomen, att ha behov av stöd och fungerande sjukvård, att livet och vardagen förändras vilket kan skapa ensamhet och isolering, att relationer förändras och ger nya förhållningssätt, att vilja orka vårda och känna oro för att inte räcka till, att känna osäkerhet och behöva ta svåra beslut. Resultatet visade att närstående saknade information, hade ett stort behov av stöd, livet och vardagen förändrades samt skapade ensamhet och isolering och relationer förändrades. Slutsatsen är att sjuksköterskor måste synliggöra närstående som en viktig del i omvårdnaden samt att ge närstående bra förutsättningar att klara det dagliga livet.

No description available.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the US alo­ne. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. Given the fact that ADHD symptoms persist in up to 50% of patients, many children receive MPH from childhood to early adulthood. Unfortunately, most of the scientific literature focuses on the short-term consequences of MPH, even though individuals are taking MPH for many years. MPH acts by blocking dopamine (DA) transporters and norepinephrine transporters, preventing the reuptake of these catecholamines following release. Previous research has shown that long-term exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We hypothesize that oxidative stress caused by the spontaneous oxidation of the excess DA in the synaptic cleft is what’s rendering dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP. Adolescent male Swiss-Webster mice were divided into three cohorts and administered either saline (control), 1 mg/kg MPH (normal dose) or 10 mg/kg (abusive dose) via intraperitoneal (IP) injections for 12 weeks. Mice were injected twice daily, Monday through Friday, mimicking a school-week dosing schedule. After 12 weeks, all animals received a drug washout period of 7 days. Then, half of each cohort was treated with MPTP (4 x 20mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Seven days after MPTP or saline treatment, the mice were sacrificed, brains were removed, and the substantia nigra (SN) and striatum (STR) were collected. Oxidative stress related to increased DA levels was determined using the glutathione assay to measure glutathione (GSH) content and near-infrared fluorescence dot blots to measure free and protein-bound ortho-quinones. GSH is an important antioxidant and thus its depletion would be indicative of oxidative stress. Additionally, since DA may be oxidized to a quinone, increases in free and protein-bound ortho-quinones also indicate oxidative stress. Interestingly, we observed a significant decrease in GSH as the dose of MPH increased with both saline and MPTP samples. Furthermore, there was a significant increase in quinones as the dose of MPH increased. In conclusion, it appears that long-term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long-term psychostimulant exposure.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the US alo­ne. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. Given the fact that ADHD symptoms persist in up to 50% of patients, many children receive MPH from childhood to early adulthood. Unfortunately, most of the scientific literature focuses on the short-term consequences of MPH, even though individuals are taking MPH for many years. Previous research has shown that long-term exposure to MPH causes dopamine-releasing neurons within the nigrostriatal pathway to die when exposed to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPH acts by blocking dopamine transporters and norepinephrine transporters, preventing the reuptake and removal of these neurotransmitters following release and increasing the time outside of the protective environment of the neuron’s vesicles. We hypothesize that spontaneous oxidation of excess dopamine to a quinone metabolite is rendering these neurons within this particular pathway to be more sensitive to MPTP. The dopamine quinone may be bound by the antioxidant glutathione (GSH) in an effort to protect the cell against oxidative stress. However, as the finite amount of GSH is depleted, the quinone may lead to the production of highly reactive molecules, leading to mitochondrial damage and cell death which may be accelerated by MPTP. In order to examine this hypothesis, we chose to study adolescent male Swiss-Webster mice, which have been shown to be resistant to MPTP’s toxic effects. They were divided into 3 cohorts and administered either saline (control), 1 mg/kg MPH (therapeutic dose) or 10 mg/kg (abusive dose) via intraperitoneal (IP) injections for 12 weeks. Mice were injected twice daily, Monday through Friday, mimicking a school-week dosing schedule. After 12 weeks, all animals received a drug washout period of 7 days. Then, half of each cohort was treated with MPTP (4 x 20 mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Either 3 or 7 days after MPTP or saline treatment, the mice were sacrificed, brains were removed, and the substantia nigra (SN) and striatum (STR) were collected. These areas of the brain make up the nigrostriatal pathway and are affected by Parkinson’s disease. Oxidative stress related to increased dopamine levels was determined using the glutathione assay to measure GSH content, near-infrared fluorescence dot blots to measure free and protein-bound ortho-quinones, and an ATP luciferase assay to measure mitochondrial function. Interestingly, there was a significant decrease in GSH as the dose of MPH was increased with both saline and MPTP samples. Furthermore, a significant increase in quinones was observed as the dose of MPH increased. We also expect to see a decrease in ATP inversely proportional to the dose of MPH indicating increased oxidative stress. In conclusion, it appears that long-term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long-term psychostimulant exposure.

No description available.

Oxidative stress is a hallmark of several aging and trauma related neurological disorders, but the precise details of how altered neuronal activity elicits subcellular redox changes have remained difficult to resolve. Current redox sensitive dyes and fluorescent proteins can quantify spatially distinct changes in reactive oxygen species levels, but multicolor probes are needed to accurately analyze compartment-specific redox dynamics in single cells that can be masked by population averaging. Our lab previously engineered a genetically-encoded red-shifted redox-sensitive fluorescent protein sensors using a Förster resonance energy transfer relay strategy. Here, we developed a second-generation excitation ratiometric sensor called rogRFP2 with improved red emission for quantitative live-cell imaging. Using this sensor to measure activity-dependent redox changes in individual cultured neurons, we observed an anticorrelation in which mitochondrial oxidation was accompanied by a concurrent reduction in the cytosol. This behavior was dependent on the activity of Complex I of the mitochondrial electron transport chain and could be modulated by the presence of co-cultured astrocytes. We also demonstrated that the red fluorescent rogRFP2 facilitates ratiometric redox imaging in Drosophila retinas. The proof-of-concept studies reported here demonstrate that this new rogRFP2 redox sensor can be a powerful tool for understanding redox biology both in vitro and in vivo across model organisms. In addition, we have used these tools that monitor cellular redox, to study oxidative stress and ROS changes in Parkinson’s disease models. Here, we have established cellular models for studying Parkinson’s disease causing LRRK2 mutations to create a platform for future work to explore the relationship between PD associated LRRK2 variants and oxidative stress.

Bakgrund: Parkinsons sjukdom är en degenerativ sjukdom som främst drabbar personer över 55 år.Sjukdomen är progressiv och påverkar motoriken, kognitionen och beteende på grund av dopaminbrist i hjärnan. Förloppet är oftast långdraget och slutar i regel med palliativ vård eftersomsjukdomen är obotbar. Trots mediciner med lindrande och bromsande effekt förändras livet radikaltför patienter med Parkinsons sjukdom. För att kunna ge trygg och adekvat vård är det viktigt attförstå patienter med parkinson upplevelse av att leva med sjukdomen. Syfte: Syftet är att beskrivapatienters upplevelse av att leva med Parkinsons sjukdom. Metod: Litteraturstudie med kvalitativansats baserad på 10 artiklar ur patientens perspektiv funna i databaserna Cinahl och Pubmed. Resultat: Tre teman med 11 tillhörande subteman analyserades fram. Sjukdomen påverkar framförallt de motoriska funktionerna men även de psykiska och sociala delarna i patienternas liv. Utöverdet påträffades även resurser för att hantera sjukdomen och hur man förlikar sig med ett liv medParkinsons sjukdom. Slutsats: Att leva med Parkinsons sjukdom ökar sårbarheten hos patienternaoch som sjuksköterska är det viktigt att ha kännedom om sjukdomen och hur den upplevs avpatienterna för att kunna ge personcentrerad och holistisk omvårdnad.

Bakgrund: Parkinsons sjukdom är världens näst vanligaste kroniska, neurologiska sjukdom, med ungefär 18 000 diagnostiserade fall i Sverige år 2016. Sjukdomen innebär en begränsad rörelseförmåga och ett minskat emotionellt välbefinnande, till exempel humörsvängningar. Syfte: Syftet var att beskriva upplevelsen av dans hos personer med Parkinsons sjukdom. Metod: En allmän litteraturstudie med en strukturerad sökmetod där 11 vetenskapliga artiklar granskades genom en innehållsanalys i fem steg. Resultat: Presenteras i fyra teman; Upplevelser av rörelseförmåga, Upplevelser av känslor, Upplevelser av självförtroende och Upplevelser av att tillhöra ett socialt sammanhang. Dansen visade på positiva effekter på rörelseförmågan och det emotionella välbefinnandet. Dans som en fysisk aktivitet kan bidra till ökat socialt sammanhang, genom att bryta social isolering. Konklusion: Dans kan förbättra rörelseförmåga, höja humöret och bidra till att personer med Parkinsons sjukdom upplever att de tillhör ett socialt sammanhang. Det är viktigt att sjuksköterskan uppmärksammar nivån av fysisk aktivitet. Ökad kunskap behövs kring hur sjuksköterskan kan motivera till fysisk aktivitet till exempel dans, eftersom det kan förbättra hälsan för personer med Parkinsons sjukdom och samtidigt minska belastningen på vården. / Background: Parkinson's disease is the world's second most common chronic, neurological disease, with approximately 18 000 diagnosed cases in Sweden in 2016. The disease entails a limited mobility and a decreased emotional well-being, for example mood swings. Aim: The aim was to describe the experience of dancing in people with Parkinson’s disease. Method: A general literature study with a structured search method, where 11 scientific articles were reviewed through a content analysis in five steps. Result: Presented in four themes; Experiences of mobility, Experiences of feelings, Experiences of self-confidence and Experiences of belonging to a social context. The dance showed positive effects on mobility and emotional well-being. Dance as a physical activity can contribute to an increasing social context, by breaking social isolation. Conclusion: Dancing can improve mobility, elevate mood and contribute to people with Parkinson's disease feeling that they belong to a social context. It is important that the nurse pays attention to the level of physical activity. Increased knowledge is needed about how the nurse can motivate to physical activity for example dance, since it can improve the health of people with Parkinson's disease and at the same time reduce the burden of care.