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. 2021 Sep 22;10:e69795. doi: 10.7554/eLife.69795

Figure 4. The AGTR1 Inhibitor olmesartan is neuroprotective in a chemically induced Gaucher disease model.

(A) Locomotor tracks of 5 dpf larvae treated 24 hr with 0.2 % DMSO, 500 µM CBE, 10 µM olmesartan, and 500 µM levodopa. The background subtraction method was used to identify and track movement for 5 min duration. (B) Quantification of total distance (in millimeters, mm) travelled during 5 min recordings for each sample group. Drugs were added at the indicated concentrations and incubated for 24 hr before behavioral recording (n = 12–13; *p < 0.05, ***p < 0.001, unpaired t test) (C) Confocal images of TH-immunoreactive DA neurons (red) and 5HT-immunoreactive serotonin neurons (green) in 6dpf larval zebrafish brains after treatments as indicated in (B). (D–E) Quantification of neurons in the demarcated regions as shown in (C). Fluorescent intensity was quantified using ImageJ and normalized against the control (0.2% DMSO) (n = 8; *p < 0.05, **p < 0.01, unpaired t test).

Figure 4—source data 1. Larval behavior total distance tracking.
TH staining quantification. 5HT staining quantification.

Figure 4.

Figure 4—figure supplement 1. Dose-dependent effects of CBE on larval zebrafish.

Figure 4—figure supplement 1.

(A) Brightfield images of 6 dpf larvae treated with CBE at varying doses (100, 500, 1000 µM) for 24 hr. No significant alterations in morphology were observed. (B–C) Confocal images of DA neurons after 24 hr of CBE treatment. Treatment with 500 µM CBE caused a significant reduction in DA neuron fluorescent intensity. CBE 1 mM was lethal to all larvae. (n = 10; p < 0.05, unpaired t test) (D) Total distance moved in a 5 min recording upon CBE treatment for 6 dpf larvae after 24 hr of chemical treatment. (n = 12, p < 0.01, unpaired t test).
Figure 4—figure supplement 2. Olmesartan and captopril are neuroprotective in a MPP+ larval zebrafish model.

Figure 4—figure supplement 2.

(A) Timeline of the MPP+ and RAAS inhibitor treatment. (B) Olmesartan and captopril treatment showed significant neuroprotection against MPP+ (n = 10–12, *p < 0.05, **p < 0.05, unpaired t test compared to MPP+ treatment alone). (C) Confocal images of ventral forebrain DA neurons in DMSO control, MPP+, and RAAS inhibitor-treated animals after 24 hr of drug treatment.