G2 - Movement Disorders: Parkinson's Disease

Objectives:

To observe a 6-hydroxydopamine (6-OHDA) neurotoxic lesion surgery as a model of Parkinson’s Disease.
To test rats with 6-OHDA neurotoxic lesion of the nigostriatal system on a number of behavioral tests.
To write a full manuscript-style lab report examining how various behaviors are altered in this model of Parkinson’s Disease.

Introduction:

Parkinson’s disease is complex neurological disorder. Although the causes of this disease are still debated, one common feature appears to be the loss of dopaminergic neurons in the substantia nigra. These dopaminergic cells typically innervate the striatum, and regulate its activity. Loss of these neurons leads to a progressive and profound loss of motor control, particularly with respect to initiation of movement. Animal models that mimic this loss may aid in the development of therapeutic interventions that could decrease the severity of the disease. The most common model of Parkinson’s Disease is neurotoxic lesions of the dopaminergic fibers in the medial forebrain bundle or the rostral striatum (Blandini et al., 2008; Deumens et al., 2002).

Preparation:

Read Kolb (2005) before the lab. Your TA will prepare the test animals ahead of time by performing the 6-OHDA neurotoxic lesion surgeries (See Appendices B and C for the procedure). Depending on local regulations, you may be invited to observe and/or participate. The same male rats used in Laboratory Exercises C and D will be used for the surgeries, allowing you to compare the behaviors both before and after the lesion. Some behaviors will be more affected than others.

Testing:

Follow the procedures outlined in Laboratory Exercises C and D with your rat. Submit the data to your TA who will collate the data from all groups. This complete data-set will be used for your write-up.

Follow-up:

In any surgical intervention, histological confirmation of the effectiveness to the surgery is important. Discuss with your TA opportunities for learning about histological procedures (perfusion, tissue slicing and staining, microscopy) that may be available. For this study, perfusion with 4% paraformaldehyde, tissue sectioning and immunohistochemical using a peroxidase stain for tyrosine hydroxylase in the striatum would be appropriate histological procedures.