[Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer's disease]

Abstract

Objective: To observe the characteristics of the interstitial fluid (ISF) drainage in the Alzheimer's disease (AD) rats through magnetic resonance imaging (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4) in the AD.

Methods: Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4^-/-) SD rats (300-350g) were divided into Sham group, AD group, Aqp4^-/--Sham group and Aqp4^-/--AD group. Sham group and Aqp4^-/--Sham group were injected with saline by intraperitoneal each day for 6 weeks, and the AD group and Aqp4^-/--AD group were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI tracer Gd-DTPA (10 mmol/L, 2 μL) was injected into the hippocampus of the rats. MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate D^*, clearance rate k' and half-life t_1/2 measured.

Results: The diffusion rate D* in Sham group was (2.66±0.36)×10^-6 mm2/s, the diffusion rate D^* in AD group was (2.72±0.62)×10-6 mm²/s, the diffusion rate D^* in Aqp4^-/--Sham group was (2.75±0.47)×10^-6 mm²/s, the diffusion rate D^* in Aqp4^-/--AD group was (2.802±0.55)×10^-6 mm²/s, and there was no statistically significant difference in the four groups (One-Way ANOVA, P>0.05).The clearance rate k' in Sham group was (4.57±0.14)×10^-4/s, the clearance rate k' in AD group was (3.68±0.22)×10^-4/s, the clearance rate k' in Aqp4^-/--Sham group was (3.17±0.16)×10^-4/s, the clearance rate k' in Aqp4^-/--AD group was (2.59±0.19)×10^-4/s, and there was significant difference in the four groups (One-Way ANOVA, P<0.05). The half-life t_1/2 in Sham group was (0.67±0.12) h, the half-life t_1/2 in AD group was (0.88±0.08) h, the half-life t_1/2 in Aqp4^-/--Sham group was (1.12±0.15) h, the half-life t_1/2 in Aqp4^-/--AD group was (1.58±0.11) h, and there was significance difference in the four groups(one-way ANOVA,P<0.05).

Conclusion: The ISF drainage is slow after AD and the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays an important role in AD to remove the metabolism of waste out of the brain.