Parkinson’s disease(PD) is a common degenerative neurological disorder. It is a brain disorder that causes unintended or uncontrollable movements. The symptoms occur when nerve cells in the basal ganglia, an area that controls movement in the brain, become impaired and/or die. When these nerve cells become impaired or die, less dopamine is produced, and causes symptoms of PD.
The four main symptoms of the diseases are:
- Tremor in hands, arms, legs, jaw, or head
- Muscle stiffness, where muscle remains contracted for a long time
- Slowness of movement
- Impaired balance and coordination, sometimes leading to falls
Other symptoms may include:
- Depression and other emotional changes
- Difficulty swallowing, chewing, and speaking
- Urinary problems or constipation
- Skin problems
For now, there is no cure for PD, but medicines, surgical treatment and different therapies can often relive some symptoms of PD. Several studies have shown the linkage between low dopamine levels and PD. Medications can help treat the symptoms of Parkinson’s by many different ways, s uch as increasing dopamine level in the brain, having an effect on brain chemicals and control non-movement symptoms. These kind of drugs can improve patients’ daily living and usually long-term medication is necessary for patients with PD. Thus, it is important to make sure the drug will not cause serious harm to the patients.
Pre-clinical studies are important before doctors can prescribe a treatment and before it can even be studied in humans. The pre-clinical studies will provide detailed information on dosing and toxicity before carrying out other studies.
Animal models for Parkinson’s disease
We used two models, the Rotenone Mouse Model and the 6-OHDA Mouse Model for researches on Parkinson’s disease(PD). Both rotenone and 6-hydroxydopamine (6-OHDA) are two drugs commonly used to generate PD animal models. Both animal models can achieve degenerative changes of dopaminergic neurons in the substantia nigra(SN), part of the basal ganglia, and satisfy the requirements for iron deposition.
The 6-OHDA-induced model is more suitable for studying dopaminergic neurons over short periods, while rotenone-induced model may be more appropriate for studying the pathological and physiological processes of Parkinson’s disease over long periods.
Rotenone Mouse Model
Rotenone is a naturally occurring toxin that inhibits complex I of the mitochondrial electron transport chain. The rotenone model of Parkinson’s Disease(PD) provides certain advantages in modelling the pathogenesis of PD.
In this model, systemic inhibition of mitochondrial complex I produces selective degeneration of the nigrostriatal dopamine system and reproduces key pathological features of clinical PD. The systemic rotenone model of PD accurately replicates many aspects of the pathology of human PD and has provided insights into pathogenesis of PD.
6-OHDA Mouse Model
6-OHDA is neurotoxins that can induce the rapid death of dopaminergic neurons in SNpc, which lead to the occurrence of some PD symptoms related to movements. The neurotoxin 6-hydroxydopamine(6-OHDA) is a classic pre-clinical model for drug screening for PD, and is widely used to introduce models of PD to investigate motor and biochemical dysfunctions in PD.
Although 6-OHDA-induced model does not include all PD symptoms, it reproduces the main cellular processes involved in PD, such as oxidative stress, neurodegeneration, neuroinflammation, and neuronal death by apoptosis.