【Animal Modeling】- Overexpression of LAMP2A in the substantia nigra improves motor function in a rhesus monkey model of Parkinson's disease

  Objective To observe the effect of overexpression of lysosome-associated membrane protein 2A in substantia nigra on chaperone-mediated autophagy on motor behavior in a rhesus monkey model of Parkinson's disease.

  Methods Seven rhesus monkeys were injected with Lewy bodies (LBs) extracts from postmortem brain tissue (voluntary donation) of PD patients in the right striatum region of seven rhesus monkeys. The PD rhesus monkey model was constructed by injecting extracts of brain tissue (voluntary donation) from non-PD patients who died. The model animals were randomly divided into two groups. The LAMP2A overexpression group (4 animals) was injected bilaterally with the adeno-associated virus vector overexpressing LAMP2A in the substantia nigra; the control group (3 animals) was injected with the control virus vector bilaterally in the substantia nigra. The motor ability of PD rhesus monkey model and the effect of LAMP2A on the motor function of PD model were evaluated by ladder test and plate feeding test. The levels of total α-synuclein (α-syn) and phosphorylated α-syn in cerebrospinal fluid and serum of experimental monkeys were determined by ELISA.

  Results The fine motor level of the left upper limbs of the rhesus monkeys in the control group decreased compared with the right side in the ladder experiment and the plate feeding experiment; the fine motor levels of the left and right upper limbs of the rhesus monkeys in the LAMP2A overexpression group did not appear significantly The levels of total α-syn and phosphorylated α-syn in the cerebrospinal fluid and serum of the control group were significantly increased at 12 months after operation by ELISA; Months later were lower than the control group in the same period.

  Conclusions Overexpression of LAMP2A may improve the fine motor ability of PD rhesus monkey model by increasing the CMA clearance of α-syn.