Parkinson’s disease (PD) is a progressive nervous system disorder that affects movement [1]. Symptoms start gradually, sometimes starting with a barely noticeable tremor in just one hand. PD signs and symptoms can be different for all that are affected. Tremors are common, but the disorder also commonly causes stiffness or slowing of movement. In PD, dopaminergic neurons in the substantia nigra of the midbrain, as well as their signaling to the striatum, gradually degrade. This degradation induces an imbalance of brain activity that leads to impaired control of voluntary muscle movements. Later stages are also associated with cognitive dysfunction. The cause of PD is unknown, but several factors appear to play a role, including genes, certain toxins (e.g. MPTP) or environmental factors. In the US, about one million people are living with PD, and ~60,000 Americans are diagnosed with PD each year. Medications (e.g. L-DOPA, galantamine, etc.) and deep brain stimulation can help control the symptoms, but PD cannot yet be cured [2, 3]. Therefore, the development of more effective therapies is necessary.
Induction: Rats or mice will be ordered at the age of ≥10 weeks old. Unilateral, intracranial injections of either 6-hydroxy dopamine (6-OHDA; 4-20 mg), adenoviral a-synuclein (AAV; 1-4 ml) or preformed a-synuclein fibrils (PFF; 5-12 mg) will be administered through a burr hole (1-2 mm in diameter) at a rate of 0.5-1 ml per minute with stereotaxic methods. The injections lead to lesions in brain areas involved in PD (e.g. striatum, medial forebrain bundle or substantia nigra).
After injection, the needle will stay in place for 5 minutes to let the substance diffuse. The needle will be withdrawn, and the animal will be removed from the stereotact. The incision will be sutured closed, and the animal will be administered 0.05 mg/kg buprenorphine XR (SC; extended release formulation) to mitigate any surgery-related pain. The animal will then be removed from anesthesia and placed on a heating pad until it regains its righting reflex. The entire procedure lasts 10-15 minutes, and the animals will be maintained and monitored for 2 weeks after their surgeries.
Figure 1: Example study design using 6-OHDA lesions in the striatum or medial forebrain bundle (MFB) in either mice or rats. SN = substantia nigra.
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