Effect of aquaporin 4 protein overexpression in nigrostriatal system on development of Parkinson’s disease

Abstract

Objects

Recent studies indicated that aquaporin 4 (AQP4), as the main water channel in the central nervous system (CNS), participated in the onset and progression of Parkinson’s disease (PD). But how the AQP4 influenced the exacerbation of PD has not been described in detail. In this study, the effect of the AQP4 protein overexpression in nigrostriatal system that include substantia nigra (SN) and striatum (CPu) on the development of PD was investigated.

Methods

Forty male Sprague Dawley rats were equally divided into two groups at random: PD group and control group, PD group undergoing surgery and receiving 6-hydroxydopamine (6-OHDA). Using MRI tracer-based method, extracellular space (ECS) diffusion parameters of nigrostriatal system for all rats were measured, including the clearance coefficient (k’) and the half-life (t_1/2). Immunohistochemistry of AQP4 was performed for 20 rats.

Results

The area of dark-stained AQP4 immunoreactivity increased markedly in SN of PD rats, there were significant differences between two groups (SN: t = 5.809, p < 0.0001; CPu: t = 5.943, p < 0.0001). And the diffusion parameters were significantly greater in PD group than that of control group, including k′ (SN: t = 5.519, p < 0.0001; CPu: t = 2.149, p = 0.045) and t_1/2 (SN: t = 6.131, p < 0.0001; CPu: t = 6.708, p < 0.0001). There was a significant positive correlation between the AQP4 expression level and the k’ values (SN: r = 0.827, p = 0.0031; CPu: r = 0.641, p = 0.0046), and a significant negative correlation between AQP4 and the t_1/2 values (SN: r=−0.654, p = 0.0403; CPu: r=-0.664, p = 0.0362).

Conclusions

The results indicated that AQP4 expression was increased in nigrostriatal system of PD rats, therefore, the overexpression of AQP4 led to acceleration of the diffusion and drainage process of drugs in ECS, reduced the effect of drugs for the treatment of PD, inhibited the development of PD.

Keywords:

• Aquaporin 4 Protein
• Parkinson’s disease
• extracellular space
• MRI
• substantia nigra
• striatum

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Beijing Brain Initiative of Beijing Municipal Science & Technology Commission (Z181100001518004); National Science Fund for Distinguished Young Scholars (61625102); Program for Training Capital Science and Technology Leading Talents (Z181100006318003)