Low-Level Domoic Acid Exposure Induces Age-like Cardiomyopathy in Young Adult and Aged Mice

Figures

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  Figure A1. Frailty index in young adult and old mice at baseline and after three weeks of treatment (domoic acid (DA) or Saline (S) controls). Frailty index was assessed in young control (black circles), young DA-treated (red circles), old control (black triangles), and old DA-treated (red triangles) mice at baseline (week 0) and after three weeks of injection. Each point represents an individual animal, and bars indicate mean ± SEM. Aged mice exhibit higher frailty compared to young mice, with changes over the 3-week intervention period reflecting treatment- and age-related effects.

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  Figure A2. Changes in cardiac diastolic (E’/A’) function and systolic function in young and aged mice following three weeks of treatment. (a) E’/A’ ratio, (b) fractional shortening (FS, %), (c) ejection fraction (EF, %), and (d) global longitudinal strain (GLS, %) measured at baseline (week 0), week 2, and week 3 in young (Y) and aged (O) mice. Data are presented for saline-treated young (SAY), domoic acid (DA)-treated young (DAY), saline-treated aged (SAO), and DA-treated aged (DAO) groups. Each point represents an individual animal; horizontal lines indicate mean ± SD. These data illustrate longitudinal changes in diastolic and systolic cardiac function and age-related differences in response to treatment over the three-week intervention period. Black symbols = saline-treated. Red symbols = DA-treated.

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  Figure 1. Reduced cardiac function after 13-week domoic acid (DA) exposure. (a) Study schematic of long-term low-level DA exposure and recovery period and example images from echocardiography used to calculate diastolic function (E’/A’, (top row)) or systolic function (% fractional shortening, (bottom row)). (b) Aging effect on diastolic function represents early to late diastole ratio (E’/A’) in young and old mice (no exposure). Diastolic function of blood flow across the mitral valve in early diastole (Ea/E’) to the flow in late diastole (Aa/A’). (c) Aging effect on systolic function represented by fractional shortening (FS%) in young and old mice (no exposure). (d,e) E’/A’ and FS% after 13-week DA exposure in young mice (SA = saline-treated; DA = domoic acid-treated). (f,g) E’/A’ and FS% after 10-week recovery period (no exposure) in young mice. * p < 0.05.

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  Figure 2. Frailty increases after three-week domoic acid (DA) exposure in both young adult and aged mice. (a) Study schematic of short-term DA exposure (three weeks). (b) Heat map showing frailty index (FI) parameters and severity after three weeks of DA or saline (SA) injections in young (Y) and old (O) mice. (c) Endpoint frailty index in young and old mice after three weeks of exposure (IP injections of saline (SA) or DA three times per week). * p < 0.05, ** p < 0.01.

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  Figure 3. Cardiac function changes after three-week domoic acid (DA) exposure in young adult and old mice. (a) Early to late diastole ratio (E’/A’), (b) % fractional shortening (FS), (c) % ejection fraction (EF), and (d) global longitudinal strain (% GLS) changes (three-week minus baseline values). Red dots = domoic acid treatment. Black dots = saline treatment. Treatment and interaction effects tested by two-way ANOVA or mixed model. * p < 0.05.

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  Figure 4. Proteomics after three-week domoic acid (DA) exposure in young adult and old mice. (a–c) Volcano plots showing differential protein expression in DA-treated young (a), DA-treated aged (b), and (c) aging only. Blue represents downregulation, red represents upregulation, and black indicates no difference. (d) Venn diagram depicting overlap of significantly differentiated proteins among saline old (SAO) vs. saline young (SAY), DA old (DAO) vs. saline old (SAO), and DA young (DAY) vs. saline young (SAY).