FIGURE

Figure 1

ID

ZDB-FIG-210927-7

Publication

Kim et al., 2021 - A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons

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Figure 1

The zebrafish NTR-MTZ chemo-genetic DA neuron ablation model suffers from mitochondrial dysfunction that can be counteracted by PD-associated mitochondrial quality control gene activity.

(A) Confocal images of ventral forebrain DA neurons in 0.2% DMSO control and 9 mM MTZ-treated 6 days post fertilization (dpf) transgenic larval zebrafish brains show significant difference in normalized fluorescent intensity (n = 10; p < 0.05, unpaired t test). The red fluorescence in the eyes is due to pigment-derived autofluorescence. (B) Long-range PCR of mitochondrial DNA versus nuclear DNA products using ventral forebrain DA neurons from control and MTZ-treated 6 dpf larval zebrafish brains anterior to the mid-hindbrain boundary (4.5 mM, 8 hrs) (n = 4 pools of 25 larval brains per pool; p < 0.01, unpaired t test). (C) Live confocal imaging of mitochondrial dynamics with mitochondria-targeted DsRed and mitochondria-targeted photoactivatable GFP in 5dpf larvae treated with 0.2% DMSO (control) or 4.5 mM MTZ for 16 hr. Arrowheads point to the elongated appearance of mitochondria in DA axons of MTZ-treated animals. (D?H) Analysis of mitochondrial dynamics including total mitochondrial count, length, % moving, velocity, and direction of movement between control and MTZ-treated samples (n = 8?10; **p < 0.01, ****p < 0.0001, unpaired t test). (I?M) Overexpression of PD-associated human genes including PARK2, PARK6, PARK7, PARK1, and associated mutant forms. mRNAs were microinjected into one-cell stage transgenic embryos and treated with 4.5 or 9 mM MTZ at 30hpf for 24 hrs to determine the neuroprotective effect of experimental conditions compared to control GFP-encoding mRNA injection (n = 10?12; *p < 0.05, **p < 0.01, ***p < 0.001, unpaired t test).

Expression Data

Genes:	DsRed2 GFP mCherry
Fish:	s2509Tg/s2509Tg th^{ion32Tg/ion32Tg}; pt420Tg/pt420Tg
Condition:	chemical treatment by environment: metronidazole
Anatomical Terms:	dopaminergic neuron mitochondrion forebrain dopaminergic neuron
Stage Range:	Day 5 to Day 6

Expression Detail

Antibody Labeling

Phenotype Data

Fish:	s2509Tg/s2509Tg c264Tg/c264Tg; s2509Tg/s2509Tg th^{ion32Tg/ion32Tg}; pt420Tg/pt420Tg
Condition:	chemical treatment by environment: metronidazole
Observed In:	dopaminergic neuron mitochondrial chromosome dopaminergic neuron mitochondrial mRNA surveillance dopaminergic neuron mitochondrion forebrain dopaminergic neuron
Stage Range:	Day 5 to Day 6

Phenotype Detail

Acknowledgments

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