Event Title

Gene Silencing of Striatal Cav 1.3 Channels can Prevent Levodopa-Induced Dyskinesia in Parkinsonian Rats

Location

Hager-Lubbers Exhibition Hall

Start Date

15-4-2019 3:30 PM

Description

PURPOSE: Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder that affects dopaminergic neurons in the brain. Levodopa, the gold standard medication for treating PD, can lead to several side effects, with Levodopa-Induced Dyskinesia (LID) as most severe. LID are abnormal and involuntary movements of the limbs and/or trunk that arise from the loss of dendritic spines of medium spiny neurons associated with the over-activity of striatal Cav 1.3 channels. Gene knockdown of Cav 1.3 channels prior to inducing parkinsonism and administration of levodopa in rats has been reported to prevent LID. The purpose of this study was to determine the amount of Cav 1.3 protein knockdown after gene silencing. CHALLENGE: Cav 1.3 protein is present in very low amounts in the brain and is therefore notoriously difficult to quantify. EXPERIENCE: Rats were given unilateral injections of either control or sh-RNA to silence Cav 1.3 channels. This was followed by induction of parkinsonism via 6-OHDA and administration of levodopa prior to LID monitoring (blinded). Rat brain tissues were sectioned and stained using fluorescent dye and Cav 1.3 protein expression was analyzed using a confocal microscope. OUTCOME: The amount of Cav 1.3 protein knockdown is an important next step after analysis of gene knockdown. Targeted gene silencing of Cav 1.3 channels can be used as therapeutic approach for preventing/potentially reversing LID in PD patients. IMPACT: This study allowed learning and development of several new skills such as tissue sectioning and staining, animal handling, and confocal microscopy.

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Apr 15th, 3:30 PM

Gene Silencing of Striatal Cav 1.3 Channels can Prevent Levodopa-Induced Dyskinesia in Parkinsonian Rats

Hager-Lubbers Exhibition Hall

PURPOSE: Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder that affects dopaminergic neurons in the brain. Levodopa, the gold standard medication for treating PD, can lead to several side effects, with Levodopa-Induced Dyskinesia (LID) as most severe. LID are abnormal and involuntary movements of the limbs and/or trunk that arise from the loss of dendritic spines of medium spiny neurons associated with the over-activity of striatal Cav 1.3 channels. Gene knockdown of Cav 1.3 channels prior to inducing parkinsonism and administration of levodopa in rats has been reported to prevent LID. The purpose of this study was to determine the amount of Cav 1.3 protein knockdown after gene silencing. CHALLENGE: Cav 1.3 protein is present in very low amounts in the brain and is therefore notoriously difficult to quantify. EXPERIENCE: Rats were given unilateral injections of either control or sh-RNA to silence Cav 1.3 channels. This was followed by induction of parkinsonism via 6-OHDA and administration of levodopa prior to LID monitoring (blinded). Rat brain tissues were sectioned and stained using fluorescent dye and Cav 1.3 protein expression was analyzed using a confocal microscope. OUTCOME: The amount of Cav 1.3 protein knockdown is an important next step after analysis of gene knockdown. Targeted gene silencing of Cav 1.3 channels can be used as therapeutic approach for preventing/potentially reversing LID in PD patients. IMPACT: This study allowed learning and development of several new skills such as tissue sectioning and staining, animal handling, and confocal microscopy.