PD Modeling and Drug Efficacy Testing Service

Disease Mechanism

Parkinson's disease (PD), also known as tremor palsy, is a common neurodegenerative disease in middle-aged and elderly people. The main lesions are in the substantia nigra and striatum. Tremor, myotonia, and hypokinesia are the main clinical features of the disease. Parkinson's disease is the fourth most common neurodegenerative disease in older adults. The main hallmarks of PD disease development are the damage of dopaminergic neurons (DAG cells) and the formation of Lewy bodies. -α- Synuclein is a soluble protein expressed in the presynaptic and perinuclear central nervous system. It is closely related to the pathogenesis and dysfunction of Parkinson's disease and is the main component of Lewy bodies.

PD Modeling

1) MPTP itself does not have neurotoxicity but has strong lipophilicity. After entering the brain, it is catalyzed by MAO-B in the mitochondrial outer membrane of the brain cells to become an intermediate product MPDP⁺, and then quickly produces spontaneous oxidation and rapidly becomes a lipophilic product Neurotoxic MPP⁺. Peripheral or intracerebral injection of MPTP can achieve massive apoptosis of DAG neurons in the midbrain, thus mimicking human PD disease. Various rat and mouse models for different research purposes can be made according to the dose, interval, method, and length of each injection.

2) 6-OHDA is a hydroxylated derivative of catecholamine. Its structure is similar to that of catecholamine. It is a specific neurotoxin and cannot pass through the blood-brain barrier. Brain injection of 6-OHDA can cause damage to the central nervous system. The injection site was the striatum-substantia nigra system. The damage mechanism is to inhibit the function of mitochondrial respiratory chain. 6-OHDA can directly inhibit the activity of mitochondrial respiratory enzyme complex I (NADH dehydrogenase) and complex IV (cytochrome oxidase), thereby inhibiting the function of the mitochondrial respiratory chain, resulting in Intracellular ATP depletion and cell death.

3) The rAAV9x virus loaded with α-synuclein wild-type (WT) and mutant (A30P, A53T) sequences were injected into the midbrain substantia nigra region of the rat by using the stereotaxic technique to establish a Parkinson's disease (PD) rat model and evaluate the model from the perspectives of etiology, histopathology, and biochemistry.

Assays after Modeling

1) Cognitive function

2) Motor function

3) Imunohistochemical detection (GFAP, ChAT, TH, c-fos, etc.), etc.

In addition to the above tests, we can also provide MRI/PET-CT in vivo imaging of small animals, cardiac ultrasound, X-ray films, tissue fluorescence imaging (whole brain slide scan, tissue immunofluorescence imaging), patch clamp on cells and brain slices, multi-channel in vivo electrophysiological recordings, respiration recordings, behavioral testing of pain, anxiety, depression, olfactory function-related (go/no-go) in awake animals.

Please feel free to contact us for more details.