Parkinson’s disease(PD) is a neurodegenerative disease that primarily affects the central nervous system and results in unintended or uncontrollable movements. The manifestation of these motor-related symptoms is due to the loss of dopaminergic neurons in the basal ganglia, the motor control center. There are several factors that contribute to Parkinson’s pathogenesis, including increased α-synuclein aggregation and mitochondrial dysfunction.
The four main symptoms of the disease are:
- Tremor in hands, arms, legs, jaw, or head
- Muscle stiffness, where the 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
Currently, there are no cures for PD. Options such as medication, surgical treatment and other forms of therapeutics are available to alleviate some of the symptoms associated with PD, such as bradykinesia. As the pathogenesis of PD involves the loss of dopamine-producing neurons, drug-based treatment aims to increase the overall level of dopamine by introducing L-DOPA, a precursor of the target neurotransmitter. There are a lot of side effects associated with this treatment, and it does not slow down the disease progression. Thus, there are ongoing R&D efforts in developing a more effective treatment.
Animal models for Parkinson’s disease
AniTech provides two types of drug-induced mouse disease models of PD: the Rotenone-induced and the 6-OHDA-induced mouse model of Parkinson’s. Both animal models can achieve degenerative changes of dopaminergic neurons in the substantia nigra(SN), part of the basal ganglia.
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 the pathogenesis of PD.
6-OHDA Mouse Model
6-OHDA is a neurotoxin that can induce the rapid death of dopaminergic neurons in SNpc, which leads 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.