Abstract
AbstractThis study aims to prepare ultrasound-targeted glial cell-derived neurotrophic factor (GDNF) retrovirus-loaded microbubbles (M pLXSN-GDNF) to verify the properties of the microbubbles and to study the therapeutic effect of the GDNF retrovirus-loaded microbubbles combined with ultrasound (U) to open the blood–brain barrier (BBB) in a Parkinson’s disease (PD) model in rats, allowing the retrovirus to pass through the BBB and transfect neurons in the substantia nigra of the midbrain, thereby increasing the expression of GDNF. The results of western blot analysis revealed significant differences between U + MpLXSN-EGFP, U + M + pLXSN-GDNF, and M pLXSN-GDNF (P < 0.05) groups. After 8 weeks of treatment, the evaluation of the effect of increased GDNF expression on behavioral deficits in PD model rats was conducted. The rotation symptom was significantly improved in the U + MpLXSN-GDNF group, and the difference before and after treatment was significant (P < 0.05). Also, the content of dopamine and the number of tyrosine hydroxylase-positive (dopaminergic) neurons were found to be higher in the brain of PD rats in the U + M pLXSN-GDNF group than in the control groups. Ultrasound combined with GDNF retrovirus-loaded microbubbles can enhance the transfection efficiency of neurons in vivo and highly express the exogenous GDNF gene to play a therapeutic role in PD model rats.
Highlights
The main pathological feature of Parkinson’s disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra of the midbrain, leading to decreased dopamine (DA) content in the striatum [1]
We prepared targeted cationic microbubbles carrying Glial cell-derived neurotrophic factor (GDNF) retrovirus to enhance the transfection efficiency of neurons in vivo and highly express the exogenous GDNF gene to play a therapeutic role in PD model rats
After the microbubbles were prepared by the mechanical vibration method, they were washed 3–4 times with phosphate-buffered saline (PBS) by the centrifugal floating method to remove the unreacted phospholipid not incorporated into microbubbles [16]
Summary
The main pathological feature of Parkinson’s disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra of the midbrain, leading to decreased dopamine (DA) content in the striatum [1]. With advances in cell and molecular biology, scientists have begun to pay attention to finding a way to delay and reverse the degeneration process of substantia nigra dopaminergic neurons. Glial cell-derived neurotrophic factor (GDNF) has been shown to promote the survival of dopaminergic neurons and protect neurons from the effect of neurotoxins, and represents a potential therapy for PD. It has been confirmed that increasing GDNF protein content in the nigrostriatal dopaminergic system can significantly improve PD symptoms in animal models [2,3].
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