Name: development of a unilaterally-lesioned 6-ohda mouse model of parkinson's disease
Uploaded: 2012-02-14T12:00:00
Description: Watch this Scientific Journal Video about Development of a Unilaterally-lesioned 6-OHDA Mouse Model of Parkinson's Disease at JoVE.com

Detta arbete stöddes av utrikesdepartementet och internationell handel (Kanadas regering), University of Toronto Connaught fonden, den kanadensiska stiftelsen för innovation, NSERC den Krembil Foundation och Cure Parkinsons Trust.

1. Bostäder och förberedelse av möss <ol><li> Upprätthålla en koloni av bakteriell artificiell kromosom (BAC) drivs transgena möss 8 (Mutant Mouse regionalt resurscentrum (MMRRC) FVB i en 12:12 h ljus-mörker-cykel med fri tillgång till mat och vatten. Dessa möss är rena FVB-möss, och är det inte nödvändigt att korsa dessa möss med någon annan stam, antingen för avel, eller för att säkerställa framgång för 6-OHDA lesion förfarande. </li><li> För att generera en parkinsonistisk modell ...

<ol>
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Detta protokoll beskriver en metod för generering av en stabil unilaterala 6-OHDA-skadade musmodell av Parkinsons sjukdom, som är extremt reproducerbar, med en hög lesion framgång, och en låg dödlighet. Framgången av 6-OHDA-lesionen kirurgi kan lätt uppskattas genom mätning av spontan rotationsbeteende med&gt; 70% ipsiversive rotationer som indikerar&gt; 95% dopaminbrist i den skadade striatum 27. Kvantifiering av striatala dopaminnivåer är de mest exakta mätningen av graden av striatal dopamin re...

<table border="1" &gt;<tbody&gt;<tr &gt;<td<strong&gt; Namn av reagens</strong</td&gt;<td<strong&gt; Företag</strong</td&gt;<td<strong&gt; Katalognummer</strong</td&gt;<td<strong&gt; Kommentarer (valfri)</strong</td&gt;</tr&gt;<tr &gt;<td&gt; Desipramin HCl</td&gt;<td&gt; Sigma-Aldrich, Oakville, ON, Kanada</td&gt;<td&gt; D125</td&gt;<td&gt; 25mg/kg</td&gt;</tr&gt;<tr&gt;<td&gt; Pargylin HCl</td&gt;<td&gt; Sigma-Aldrich, Oakville, ON, Kanada</td&gt;<td&gt; P8013</td&gt;<td&gt; 5mg/kg</td&gt;</tr&gt;<tr&gt;<td&gt; 6-OHDA HBr</td&gt;<td&gt; Sigma-Aldrich, Oakville, ON, Kanada</td&gt;<td&gt; H116</td&gt;<td&gt; 3 mg / mus</td&gt;</tr&gt;<tr&gt;<td&gt; Stereotaktisk ram</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Modell 900</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Mus öronkåpor</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Modell 921 Zygoma öronkåpor</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Mus framtand bar</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Modell 923B</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Mus anestesimask</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Modell 923B</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Priming kit (innehållande 250 ml spruta)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; PRMKIT 81.120</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; RN klämringskoppling kit (1 mm)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55.750-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; PEEK slang från RN klämringskoppling kit<
 (1/16<sup&gt; Te</sup&gt; Tum)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55.751-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Dual liten hubb RN Coupler</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55.752-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Luer till små hubb RN-adapter</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55.753-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; 1 ml spruta 25S modell 7001KH</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 80.100</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; * 33G löstagbar nål (RN) 6-pack. . Anpassad 1 tum med 45 &lt;° avfasning</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 7803-05</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Saxar</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada.</td&gt;<td&gt; 14.084-08</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Skalpell</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada</td&gt;<td&gt; 10.003-12</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Skalpellblad</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada</td&gt;<td&gt; 10.035-20</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Forcep</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada</td&gt;<td&gt; 11.608-15</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Hemostater</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada.</td&gt;<td&gt; 13.004-14</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Isofluran</td&gt;<td&gt; Abbot</td&gt;<td&gt; 02241315</td&gt;<td&gt; 2-3%</td&gt;</tr&gt;<tr&gt;<td&gt; Suters (Vicryl 4,0)</td&gt;<td&gt; Syneture</td&gt;<td&gt; SS-683</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Sterilisator</td&gt;<td&gt; Fina Science Tools, Vancouver, BC, Kanada</td&gt;<td&gt; 18.000-45</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Infusion Pump</td&gt;<td&gt; Harvard Apparatus</td&gt;<td&gt; PhD 22/2000</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Needles (27G)</td&gt;<td&gt; Becton Dickinson</td&gt;<td&gt; 305.109</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Needles (25G)</td&gt;<td&gt; Becton Dickinson</td&gt;<td&gt; 305.127</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Sprutor (1 ml)</td&gt;<td&gt; BD spruta</td&gt;<td&gt; 309.692</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Anestesi vagnen</td&gt;<td&gt; LEI medicinsk</td&gt;<td&gt; M2000</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Baytril</td&gt;<td&gt; CDMV, St Hyacinthe, QC</td&gt;<td&gt; 102.207</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Lidokain</td&gt;<td&gt; CDMV, St Hyacinthe, QC</td&gt;<td&gt; 3914</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Betadinlösning</td&gt;<td&gt; CDMV, St Hyacinthe, QC</td&gt;<td&gt; 19.955</td&gt;<td&gt;</td&gt;</tr&gt;</tbody&gt;</table

development of a unilaterally-lesioned 6-ohda mouse model of parkinson's disease

Den ensidigt lesion 6-hyroxydopamine (6-OHDA)-skadade råttmodell av Parkinsons sjukdom (PD) har visat sig vara ovärderligt för att föra vår förståelse av mekanismerna bakom parkinsonsymtom, eftersom den sammanfattas de förändringar i basala ganglierna kretsar och farmakologi observerats i patienter med Parkinsons sjukdom 1-4. Men de exakta cellulära och molekylära förändringar som sker vid kortiko-striatala synapser för de utgående vägar inom striatum, vilket är den största ingången regionen i basala ganglierna förblir svårfångad, och detta tros vara platsen där patologiska avvikelser som ligger bakom parkinsonsymtom uppstår 3 , 5. I PD, har förstå de mekanismer som ligger bakom förändringarna i basala ganglierna kretsar efter degeneration av Nigro-striatala vägen blivit mycket fram genom utvecklingen av bakteriell artificiell kromosom (BAC) möss över uttrycker gröna fluorescerande proteiner som drivs av att främjars specifika för de två striatala utgående vägar (direkt väg: EGFP-D1, indirekta vägen: EGFP-D2 och EGFP-A2a) 8, vilket gör att de kan studeras isolerat. Till exempel har senare studier antytt att det finns sjukliga förändringar i synaptisk plasticitet i Parkinson möss 9,10. Men dessa studier utnyttjas unga möss och akuta modeller av parkinsonism. Det är oklart om de förändringar som beskrivs i vuxna råttor med stabila 6-OHDA lesioner förekommer även i dessa modeller. Andra grupper har försökt skapa en stabil ensidigt-skadade 6-OHDA modell vuxen mus av PD genom att skada den mediala framhjärnan bunt (MFB), tyvärr var dödligheten i denna studie extremt hög, med endast 14% överlevande operationen för 21 dagar eller längre 11. Nyare studier har genererats inom nigrala lesioner med både en låg dödlighet&gt; 80% förlust av dopaminerga neuroner, men expression av L-DOPA-inducerad dyskinesi 11,12,13,14 var variabeli dessa studier. En annan väl etablerad musmodell av PD är den MPTP-lesionerad mus 15. Även denna modell har visat sig användbar vid bedömningen av potentiella nervskyddande ämnen 16, är det mindre lämpligt för att förstå mekanismerna bakom symtom på PD, eftersom denna modell ofta misslyckas med att framkalla motoriska brister, och visar en bred variation i omfattningen av skadan 17, 18 . Här har vi utvecklat en stabil unilaterala 6-OHDA-skadade musmodell av PD genom direkt administrering av 6-OHDA i MFB, som genomgående ger&gt; 95% förlust av striatal dopamin (mätt med HPLC), såväl som framställning av beteendemässiga obalanser observerades i väl karaktäriserade unilaterala 6-OHDA-skadade råttmodell av PD. Denna nyutvecklade musmodell av PD kommer att visa sig vara ett värdefullt verktyg för att förstå mekanismerna bakom generation parkinsonsymtom.

Watch this Scientific Journal Video about Development of a Unilaterally-lesioned 6-OHDA Mouse Model of Parkinson's Disease at JoVE.com

Development of a Unilaterally-lesioned 6-OHDA Mouse Model of Parkinson's Disease

Ett protokoll för att utföra ensidigt 6-OHDA-lesioner i den mediala forebrain bundle i möss beskrives. Denna metod har en låg dödlighet (13,3%) med 89% av de överlevande djuren visade&gt; 95% förlust av striatal dopamin och 90,63 ± -4,02% ipsiversive roterande inriktning mot sidan av lesionen.

Utvecklingen av en ensidigt-lesionerad 6-OHDA-musmodell av Parkinsons sjukdom

The unilaterally lesioned 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) has proved to be invaluable in advancing our ...

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Medicine

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Skin Punch Biopsy Explant Culture for Derivation of Primary Human Fibroblasts

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A  simple procedure to intubate mice for pulmonary function measurements would  have several advantages in longitudinal studies with limited numbers or  ...

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

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Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer&#39;s disease, but its effects in Parkinson&#39;s disease ...

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Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. ...

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

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The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

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En neonatal mus ryggmärgskompression skada Modell

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Utveckling av en Alpha-synuklein Based råttmodell för Parkinsons sjukdom via stereotaktisk injektion av en rekombinant adeno-associerad viral vektor

In order to study the molecular pathways of Parkinson&#39;s disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on ...