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

Dette arbejde blev støttet af Institut for udenrigsanliggender og international handel (Canadas regering), University of Toronto Connaught fond, den canadiske Institut for Innovation, NSERC, den Krembil Foundation og Cure Parkinsons Trust.

1. Boliger og forberedelse af mus <ol><li> Oprethold en koloni af bakteriel kunstigt kromosom (BAC) drevet transgene mus 8 (Mutant Mouse Regional Resource Center (MMRRC) FVB i en 12:12 h lys-mørke cyklus med fri adgang til mad og vand. Disse mus er rene FVB mus, og Det er ikke nødvendigt at krydse disse mus med en anden stamme, enten til avl, eller for at sikre vellykket 6-OHDA læsion procedure. </li><li> For at generere et parkinsonlignende model er voksne mus i alderen postnatal dag 31-42 (P31-42), der...

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Denne protokol beskrives en fremgangsmåde til generering af en stabil unilaterale 6-OHDA-læderede musemodel af Parkinsons sygdom, hvilket er meget reproducerbar, med en høj læsion succesrate, og en lav dødelighed. Succes 6-OHDA læsion kirurgi kan let vurderes ved måling af spontan roterende adfærd med&gt; 70% ipsiversive omdrejninger indikative på&gt; 95% dopaminudtømning i den læderede striatum 27. Kvantificering af striatale dopaminniveauer er den mest nøjagtige måling af omfanget af striatal d...

<table border="1" &gt;<tbody&gt;<tr &gt;<td<strong&gt; Navn på reagenset</strong</td&gt;<td<strong&gt; Firma</strong</td&gt;<td<strong&gt; Katalog nummer</strong</td&gt;<td<strong&gt; Kommentarer (valgfri)</strong</td&gt;</tr&gt;<tr &gt;<td&gt; Desipramin HCI</td&gt;<td&gt; Sigma-Aldrich, Oakville, ON, Canada</td&gt;<td&gt; D125</td&gt;<td&gt; 25mg/kg</td&gt;</tr&gt;<tr&gt;<td&gt; Pargylin HCI</td&gt;<td&gt; Sigma-Aldrich, Oakville, ON, Canada</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, Canada</td&gt;<td&gt; H116</td&gt;<td&gt; 3 mg / mus</td&gt;</tr&gt;<tr&gt;<td&gt; Stereotaktisk ramme</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Model 900</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Musen øre kopper</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Model 921 Zygoma ørekopper</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Mus fortandsstangen</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Model 923B</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Mus anæstesi maske</td&gt;<td&gt; Kopf Instruments, Tujunga, CA, USA</td&gt;<td&gt; Model 923B</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Priming Kit (indeholdende 250 ml sprøjte)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; PRMKIT 81120</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; RN kompressionsfitting kit (1 mm)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55750-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; PEEK slangen fra RN kompressionsfitting kit<
 (1/16<sup&gt; Th</sup&gt; Inch)</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55751-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Dual lille hub RN Coupler</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55752-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Luer til lille nav RN adapter</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 55753-01</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; 1 ml 25S sprøjte model 7001KH</td&gt;<td&gt; Hamilton Company, Reno, NV, USA</td&gt;<td&gt; 80100</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; * 33G aftagelig kanyle (RN) pakke af 6. . Custom 1 tommer med 45 &lt;° facet</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; Saks</td&gt;<td&gt; Fine Science Tools, Vancouver, BC, Canada.</td&gt;<td&gt; 14084-08</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Skalpel</td&gt;<td&gt; Fine Science Tools, Vancouver, BC, Canada</td&gt;<td&gt; 10003-12</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Skalpelblade</td&gt;<td&gt; Fine Science Tools, Vancouver, BC, Canada</td&gt;<td&gt; 10035-20</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Forcep</td&gt;<td&gt; Fine Science Tools, Vancouver, BC, Canada</td&gt;<td&gt; 11608-15</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Hemostats</td&gt;<td&gt; Fine Science Tools, Vancouver, BC, Canada.</td&gt;<td&gt; 13004-14</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; Fine Science Tools, Vancouver, BC, Canada</td&gt;<td&gt; 18000-45</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Infusion Pumpe</td&gt;<td&gt; Harvard Apparatus</td&gt;<td&gt; Ph.d.-22/2000</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Nåle (27g)</td&gt;<td&gt; Becton Dickinson</td&gt;<td&gt; 305109</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Nåle (25G)</td&gt;<td&gt; Becton Dickinson</td&gt;<td&gt; 305127</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Injektionssprøjter (1 ml)</td&gt;<td&gt; BD sprøjte</td&gt;<td&gt; 309692</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Anæstesi vogn</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; 102207</td&gt;<td&gt;</td&gt;</tr&gt;<tr&gt;<td&gt; Lidocain</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; Betadinopløsning</td&gt;<td&gt; CDMV, St. Hyacinthe, QC</td&gt;<td&gt; 19955</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 læderet 6-hyroxydopamine (6-OHDA)-læderede rotte model af Parkinsons sygdom (PD), har vist sig at være uvurderlig i at fremme vores forståelse af de mekanismer, der ligger parkinson symptomer, da den redegør for de ændringer i basalganglierne kredsløb og farmakologi observeret i patienter med Parkinsons sygdom 1-4. Den nøjagtige cellulære og molekylære forandringer i cortico-striatale synapser i output pathways i striatum, som er den største bidrag region af basalganglierne forbliver uklar, og dette menes at være stedet, hvor patologiske afvigelser ligger parkinson symptomerne opstår 3 , 5. I PD er forstå de mekanismer, der ligger ændringer i basalganglierne kredsløb efter degeneration af den nigro-striatale pathway i høj grad blevet fremført af udviklingen af ​​bakterielle kunstige kromosomer (BAC)-mus over-udtrykker grønt fluorescerende proteiner, som drives af fremmers specifikke for de to striatale output veje (direkte vej: EGFP-D1 indirekte vej: EGFP-D2 og EGFP-A2a) 8, giver dem mulighed for at blive undersøgt i isolation. For eksempel har nylige undersøgelser antydet, at der er patologiske ændringer i synaptisk plasticitet hos Parkinson mus 9,10. Disse undersøgelser anvendes juvenile mus og akutte modeller af parkinsonisme. Det er uklart, om de beskrevne ændringer i voksne rotter med stabile 6-OHDA-læsioner forekommer også i disse modeller. Andre grupper har forsøgt at skabe et stabilt ensidigt-læderede 6-OHDA voksen musemodel af PD ved læsion af mediale forhjernen bundt (MFB), desværre dødeligheden i dette studie var ekstremt høj, med kun 14% overlever operationen for 21 dage eller længere 11. Nyere undersøgelser har genereret inden nigrale læsioner med både en lav dødelighed&gt; 80% tab af dopaminerge neuroner, men ekspression af L-DOPA-induceret dyskinesi 11,12,13,14 var variabeli disse forsøg. Anden veletableret musemodel for PD er den MPTP-læderede mus 15. Mens denne model har vist sig nyttig ved vurderingen af potentielle neurobeskyttende midler 16, er mindre egnet til at forstå mekanismerne bag symptomer på PD, som det model ofte ikke at inducere motoriske mangler, og viser en bred variation i graden af læsionen 17, 18 . Her har vi udviklet en stabil unilaterale 6-OHDA-læderede musemodel for PD ved direkte administrering af 6-OHDA i MFB, som konsekvent forårsager&gt; 95% tab af striatal dopamin (som målt ved HPLC) såvel som fremstilling af adfærdsmæssige ubalancer observeret i velkarakteriserede unilaterale 6-OHDA-læderede rottemodel for PD. Denne nyudviklede musemodel af PD vil vise sig et værdifuldt værktøj til at forstå de mekanismer, der ligger generation af Parkinsons symptomer.

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

En protokol til udførelse unilaterale 6-OHDA-læsioner i den mediale forhjernen bundtet i mus er beskrevet. Denne fremgangsmåde har en lav dødelighed (13,3%) med 89% af de overlevende dyr, som udviser&gt; 95% tab af striatal dopamin og 90,63 ± -4,02% ipsiversive roterende forspænding mod den side af læsionen.

Udvikling af en ensidigt-læderede 6-OHDA-musemodellen af ​​Parkinsons sygdom

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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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 Mouse rygmarvskompression Skade Model

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Development of an Alpha-synuclein Based Rat Model for Parkinson's Disease via Stereotactic Injection of a Recombinant Adeno-associated Viral Vector

Udvikling af en Alpha-synuclein Based rottemodel for Parkinsons sygdom via Stereotaktisk injektion af et Rekombinant adenoassocieret 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 ...

Udvikling af en ensidigt-læderede 6-OHDA-musemodellen af ​​Parkinsons sygdom

Udvikling af en ensidigt-læderede 6-OHDA-musemodellen af Parkinsons sygdom