Models of Parkinson's Disease (PD)

Parkinson’s disease is a chronic neurodegenerative disorder characterized by dopaminergic (DA) neuron death in the substantia nigra compacta (SNc) and the accumulation of aggregated α-synuclein (α-syn) into Lewy bodies (LBs). To date, there is no cure for PD, but there are medications to address some of the symptoms. Greentech offers validated animal models of Parkinson’s disease for studies of biological mechanisms and assessment of novel therapies.

Figure 1. Neuropathology of Parkinson's Disease (Dauer & Przedborski 2003).

Our Animal Models of Parkinson's Disease

1. MPTP Induced Parkinson's Disease Model

The 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a dopaminergic pyridine neurotoxin, has been commonly used to mimic Parkinson's disease in mice. The MPTP induced mouse model of Parkinson's disease is a cost-saving and time-efficient solution for PD research. MPTP-induced parkinsonism in the monkey is considered as the gold standard PD model because it reproduces some of the critical pathophysiological and behavioral alterations in humans.

Induction: intramuscular injection, intravenous injection, intraperitoneal injection, cervical artery injection, or injection into the substantia nigra.

Animal Species: mice, non-human primates (NHPs)

Disease Characteristics: MPTP-induced PD model exhibits neuropathology similar to PD, including nigrostriatal dopaminergic cell death and loss of their neurotransmitter, dopamine (DA), in the striatum.

2. 6-OHDA Induced PD Model

6-hydroxydopamine (6-OHDA) is a catecholamine neurotoxin, widely used for modeling degeneration of dopaminergic neurons in PD. Since 6-OHDA cannot cross the BBB, it is often administered locally into the striatum, SNpc, or medial forebrain bundle (MFB) to establish unilateral 6-OHDA lesion rat model.

Induction: injection of 6-OHDA into the substantia nigra or MFB

Animal Species: rats

Disease Characteristics: degeneration of dopaminergic neurons and decrease in tyrosine hydroxylas (TH) activity in the striatum

3. Transgenic PD Mouse Model

The α-synuclein A53T is the major component of LBs. Multiple α-synuclein transgenic mouse models have been generated to clarify its physiological and pathologic functions. These transgenic mice overexpress either wild-type or PD-associated mutated human α-synuclein (such as A53T, A30P) under the control of PDGF, Prnp or mThy1 promoter, to mimic pathological features of PD patients.

Animal Species: PDGF-SNCA (A53T) transgenic mice, Prnp-SNCA (A53T) transgenic mice, mThy1-SNCA transgenic mice

Disease Characteristics: α-syn inclusions distributed in multiple places, slight degradation of hydroxylase-positive fibers in the striatum

Positive Drug

L-dopamine

Clinical Assessment of PD Models

      1) Blood routine and biochemistry

      2) Open field, Pole test

      3) MRI imaging or SPECT imaging

      4) Biomarker analysis: DA and its metabolites

      5) Histopathology: H&E staining, immunohistochemistry (TH neuron)

Representative Study

1. 6-OHDA-Induced Rat Parkinson's Disease Model

Figure 1. Stereotaxic intracranial injection of 6-hydroxydopamine (6-OHDA) for establishment of a unilateral rat Parkinson's disease (PD) model.

Figure 2. Behavioral assessments in the 6-OHDA-induced rat Parkinson's disease model, including spontaneous locomotor activity, apomorphine-induced rotational behavior, and the cylinder test.

Figure 3. Tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of the 6-OHDA-induced rat Parkinson's disease model.

2. MPTP-Induced Subacute Mouse Parkinson's Disease Model

Figure 4. Pharmacodynamic evaluation of the MPTP-induced subacute mouse Parkinson's disease model, including rotational behavior, grip strength, striatal dopamine (DA) levels, and TH-positive fiber density in the striatum.

3. MPTP-Induced Chronic Mouse Parkinson's Disease Model

Figure 5. Pharmacodynamic evaluation of the MPTP-induced chronic mouse Parkinson's disease model, including grip strength and TH-positive fiber density in the striatum.

References

1. Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc. 2007;2(1):141–51.

2. Beal M F. Experimental models of Parkinson's disease[J]. Nature reviews neuroscience, 2001, 2(5): 325-332.

3.  Betarbet R, Sherer T B, Greenamyre J T. Animal models of Parkinson's disease[J]. Bioessays, 2002, 24(4): 308-318.

4. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models[J]. Neuron, 2003, 39(6): 889-909.

Inquiries

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