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Early life adversity drives sex‐specific anhedonia and meningeal immune gene expression through mast cell activation

Duque-Wilckens, Natalia, Teis, Robert, Sarno, Erika, Stoelting, Frauke, Khalid, Sonia, Dairi, Zakaria, Douma, Alex, Maradiaga, Nidia, Hench, Stina, Dharshika, Christine D., Thelen, Kyan M., Gulbransen, Brian, Robison, A.J., Moeser, Adam J.·2022·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2022.03.009PMC PMC9149134
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Fig. 1. NMSEW plus adult stress reduces sucrose preference in females but not males, and administration of Ketotifen exerts sex and treatment specific effects. A. Experimental timeline. B. Three-way ANOVA assessing effects of sex, early life treatment, adult treatment and their interaction on sucrose preference behavior followed by Fisher LSD. *p < 0.05.
Fig. 1. NMSEW plus adult stress reduces sucrose preference in females but not males, and administration of Ketotifen exerts sex and treatment specific effects. A. Experimental timeline. B. Three-way ANOVA assessing effects of sex, early life treatment, adult treatment and their interaction on sucrose preference behavior followed by Fisher LSD. *p < 0.05.CC BY-NC-ND · PubMed Central
Fig. 2. NMSEW exerts sex-specific effects on dura mater gene expressionThree-way ANOVA assessing effects of sex, early life treatment, adult treatment and their interaction on the dura mater gene expression of A. mast cell-specific protease cma1, B. the rate limiting enzyme for histamine synthesis hdc, C. the inflammatory cytokines il-6 and D. tnf alpha, E. the tryptophan catalizing enzyme tph1, and F. the mouse endothelial growth factor vegf-c followed by Fisher LSD. *p < 0.05, **p < 0.01 ***p=<0.001, ****p < 0.0001.
Fig. 2. NMSEW exerts sex-specific effects on dura mater gene expressionThree-way ANOVA assessing effects of sex, early life treatment, adult treatment and their interaction on the dura mater gene expression of A. mast cell-specific protease cma1, B. the rate limiting enzyme for histamine synthesis hdc, C. the inflammatory cytokines il-6 and D. tnf alpha, E. the tryptophan catalizing enzyme tph1, and F. the mouse endothelial growth factor vegf-c followed by Fisher LSD. *p < 0.05, **p < 0.01 ***p=<0.001, ****p < 0.0001.CC BY-NC-ND · PubMed Central
Fig. 3. Administration of Ketotifen does not affect dura mater gene expression in NH animals. A. Experimental timeline. B-G. No effects of Ketotifen are seen on expression of cma1, hdc,il-6,tnf alpha, tph1, or vegf-c in NH males or females.
Fig. 3. Administration of Ketotifen does not affect dura mater gene expression in NH animals. A. Experimental timeline. B-G. No effects of Ketotifen are seen on expression of cma1, hdc,il-6,tnf alpha, tph1, or vegf-c in NH males or females.CC BY-NC-ND · PubMed Central
Fig. 4. Mast cells are not homogeneous across dura mater regions. A: diagram showing regions of dura mater analyzed:: parietal, interparietal, Sagittal sinus and Transverse sinus. B: Total mast cell (MC) number per mm2 significantly differs by dura mater region, with interparietal region showing the highest mast cell density. C: Activation level of mast cells differs by dura mater region, with transverse region showing the highest activation. D: Relative expression of pseudopodia varies by dura mater region, with interparietal region showing the highest expression. One way ANOVA followed by Dunnett’s multiple comparisons test, **p < 0.01, ****p < 0.0001. n = 49–52 per group.
Fig. 4. Mast cells are not homogeneous across dura mater regions. A: diagram showing regions of dura mater analyzed:: parietal, interparietal, Sagittal sinus and Transverse sinus. B: Total mast cell (MC) number per mm2 significantly differs by dura mater region, with interparietal region showing the highest mast cell density. C: Activation level of mast cells differs by dura mater region, with transverse region showing the highest activation. D: Relative expression of pseudopodia varies by dura mater region, with interparietal region showing the highest expression. One way ANOVA followed by Dunnett’s multiple comparisons test, **p < 0.01, ****p < 0.0001. n = 49–52 per group.CC BY-NC-ND · PubMed Central
Fig. 5. NMSEW plus adult stress induces histological changes in dura mater mast cells. A. Experimental timeline. B. Photomicrograph showing subregions of dura mater and examples of mast cell features quantified: active mast cell (orange arrows), inactive mast cell (black arrows), and presence of pseudopodia (red arrows). C, G, K, O. Photomicrograph showing examples of mast cells in interparietal, parietal, sagittal sinus, and transverse sinus regions, respectively. D, F. Compared to NH plus adult stress (NH + St), NMSEW plus adult stress (NMSEW + St) increases total mast cell number (two way ANOVA main effect of early life treatment, *p = 0.03) and reduces relative pseudopodia expression (two way ANOVA main effect of early life treatment, *p = 0.01) in the interparietal dura mater.I. In the parietal region, NH males showed increased activation levels compared to NH females (Šídak’s multiple comparisons test *p = 0.003), and NMSEW reduced the activation level in males only (Šídák’s multiple comparisons test *p = 0.01) N. NMSEW increases relative pseudopodia expression in the sagittal sinus region (two way ANOVA main effect of early life treatment, *p = 0.01). Q. Females show increased activation levels of mast cells located in the transverse sinus region (two way ANOVA main effect of sex, *p = 0.02).
Fig. 5. NMSEW plus adult stress induces histological changes in dura mater mast cells. A. Experimental timeline. B. Photomicrograph showing subregions of dura mater and examples of mast cell features quantified: active mast cell (orange arrows), inactive mast cell (black arrows), and presence of pseudopodia (red arrows). C, G, K, O. Photomicrograph showing examples of mast cells in interparietal, parietal, sagittal sinus, and transverse sinus regions, respectively. D, F. Compared to NH plus adult stress (NH + St), NMSEW plus adult stress (NMSEW + St) increases total mast cell number (two way ANOVA main effect of early life treatment, *p = 0.03) and reduces relative pseudopodia expression (two way ANOVA main effect of early life treatment, *p = 0.01) in the interparietal dura mater.I. In the parietal region, NH males showed increased activation levels compared to NH females (Šídak’s multiple comparisons test *p = 0.003), and NMSEW reduced the activation level in males only (Šídák’s multiple comparisons test *p = 0.01) N. NMSEW increases relative pseudopodia expression in the sagittal sinus region (two way ANOVA main effect of early life treatment, *p = 0.01). Q. Females show increased activation levels of mast cells located in the transverse sinus region (two way ANOVA main effect of sex, *p = 0.02).CC BY-NC-ND · PubMed Central

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Cited by

Sorted by citations

Metadata

Authors
Duque-Wilckens, N., Teis, R., Sarno, E., Stoelting, F., Khalid, S., Dairi, Z., Douma, A., Maradiaga, N., Hench, S., Dharshika, C. D., Thelen, K. M., Gulbransen, B., Robison, A. J., & Moeser, A. J.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2022-07
Volume
103
Pages
73-84
ISSN
0889-1591
DOI
10.1016/j.bbi.2022.03.009
PMC
PMC9149134
Cited by
27
References
18
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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