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Elevated emotional contagion in a mouse model of Alzheimer ’ s disease is associated with increased synchronization in the insula and amygdala

View Article: PubMed Central - PubMed

ABSTRACT

Emotional contagion, a primitive form of empathy, is heightened in patients with Alzheimer’s disease (AD); however, the mechanism underlying this attribute has not been thoroughly elucidated. In this study, observational fear conditioning was performed to measure emotional contagion levels in a mouse model of AD. Simultaneous recording of local field potentials in the bilateral anterior insula, basolateral amygdala, anterior cingulate cortex, and retrosplenial cortex was also conducted to investigate related brain network changes. Consistent with the results obtained with AD patients, 11-month-old AD model mice exhibited significantly higher freezing levels in observational fear conditioning, indicating elevated emotional contagion compared to age-matched wild-type mice. Furthermore, the left anterior insula and right basolateral amygdala of 11-months-old AD model mice indicated sustained increases in synchronization when they observed the suffering of conspecifics. These changes did not appear in other age groups or wild-type controls. Additionally, the amyloid plaque burden within the anterior insula was significantly correlated with the freezing levels in observational fear conditioning. Taken together, this study reveals increased and sustained network synchrony between the anterior insula and basolateral amygdala, which comprise a salience network in humans, as a potential mechanism for elevated emotional contagion in a mouse model of AD.

No MeSH data available.


Related in: MedlinePlus

Plaque burden in the AI of Tg mice is highly correlated with the level of fear response in OFC.(A,B) Examples of amyloid plaque deposition in the AI (A) and BLA (B) of Tg-3, Tg-7, and Tg-11 mice. All brain slice samples were stained with thioflavin-S. Turquoise was used as a pseudo-colour for amyloid plaque. (C,D) Average plaque burden of the AI (C) and BLA (D) were quantified in Tg-3, Tg-7, and Tg-11 mice. (C) In the AI, all three age groups showed significant differences between each pair of groups (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (D) Plaque burden in the BLA of Tg-11 mice showed significantly higher than that of Tg-3 or Tg-7 mice (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (E,F) Plaque burden in the AI (E; rs = 0.729, P < 0.0001) and BLA (F; rs = 0.682, P < 0.0001) showed a significant correlation with the freezing levels in OFC. Spearman’s correlation was used for the significance test. (G) The correlation coefficient of the AI was significantly higher than that of the RSC or ACC (*P < 0.05, Steiger’s z-test). Data are presented as the mean ± SEM.
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f4: Plaque burden in the AI of Tg mice is highly correlated with the level of fear response in OFC.(A,B) Examples of amyloid plaque deposition in the AI (A) and BLA (B) of Tg-3, Tg-7, and Tg-11 mice. All brain slice samples were stained with thioflavin-S. Turquoise was used as a pseudo-colour for amyloid plaque. (C,D) Average plaque burden of the AI (C) and BLA (D) were quantified in Tg-3, Tg-7, and Tg-11 mice. (C) In the AI, all three age groups showed significant differences between each pair of groups (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (D) Plaque burden in the BLA of Tg-11 mice showed significantly higher than that of Tg-3 or Tg-7 mice (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (E,F) Plaque burden in the AI (E; rs = 0.729, P < 0.0001) and BLA (F; rs = 0.682, P < 0.0001) showed a significant correlation with the freezing levels in OFC. Spearman’s correlation was used for the significance test. (G) The correlation coefficient of the AI was significantly higher than that of the RSC or ACC (*P < 0.05, Steiger’s z-test). Data are presented as the mean ± SEM.

Mentions: To identify correlations between the OFC freezing levels and the amyloid plaque burden, the plaque area was quantified at the AI, BLA, RSC, and ACC of all groups (Fig. 4A,B; Supplementary Fig. S6A,B). No accumulation was observed in Wt-3, Wt-7, and Wt-11 mice. Although amyloid plaques were not observed in Tg-3 mice, these structures appeared in Tg-7 mice and were significantly increased in Tg-11 mice at the AI (Fig. 4C; ***P < 0.001). In the BLA, there was no difference between Tg-3 and Tg-7 mice, but Tg-11 mice showed a significantly higher plaque burden compared with Tg-3 or Tg-7 animals (Fig. 4D; ***P < 0.001). The RSC and ACC also showed significant increases in plaque burden with increasing age of the Tg mice (Supplementary Fig. S6C,D). The plaque burden in the AI showed the highest correlation with OFC freezing levels (Fig. 4E; rs = 0.729, P < 0.0001). Other regions also showed significant correlations with OFC freezing levels (Fig. 4F; P < 0.0001; Supplementary Fig. S6E,F; P < 0.001), but the correlation coefficient of the AI was significantly higher than that of the RSC and ACC (Fig. 4G; *P < 0.05).


Elevated emotional contagion in a mouse model of Alzheimer ’ s disease is associated with increased synchronization in the insula and amygdala
Plaque burden in the AI of Tg mice is highly correlated with the level of fear response in OFC.(A,B) Examples of amyloid plaque deposition in the AI (A) and BLA (B) of Tg-3, Tg-7, and Tg-11 mice. All brain slice samples were stained with thioflavin-S. Turquoise was used as a pseudo-colour for amyloid plaque. (C,D) Average plaque burden of the AI (C) and BLA (D) were quantified in Tg-3, Tg-7, and Tg-11 mice. (C) In the AI, all three age groups showed significant differences between each pair of groups (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (D) Plaque burden in the BLA of Tg-11 mice showed significantly higher than that of Tg-3 or Tg-7 mice (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (E,F) Plaque burden in the AI (E; rs = 0.729, P < 0.0001) and BLA (F; rs = 0.682, P < 0.0001) showed a significant correlation with the freezing levels in OFC. Spearman’s correlation was used for the significance test. (G) The correlation coefficient of the AI was significantly higher than that of the RSC or ACC (*P < 0.05, Steiger’s z-test). Data are presented as the mean ± SEM.
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Related In: Results  -  Collection

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f4: Plaque burden in the AI of Tg mice is highly correlated with the level of fear response in OFC.(A,B) Examples of amyloid plaque deposition in the AI (A) and BLA (B) of Tg-3, Tg-7, and Tg-11 mice. All brain slice samples were stained with thioflavin-S. Turquoise was used as a pseudo-colour for amyloid plaque. (C,D) Average plaque burden of the AI (C) and BLA (D) were quantified in Tg-3, Tg-7, and Tg-11 mice. (C) In the AI, all three age groups showed significant differences between each pair of groups (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (D) Plaque burden in the BLA of Tg-11 mice showed significantly higher than that of Tg-3 or Tg-7 mice (P < 0.0001 (age), one-way ANOVA, ***P < 0.001, Bonferroni’s post hoc test). (E,F) Plaque burden in the AI (E; rs = 0.729, P < 0.0001) and BLA (F; rs = 0.682, P < 0.0001) showed a significant correlation with the freezing levels in OFC. Spearman’s correlation was used for the significance test. (G) The correlation coefficient of the AI was significantly higher than that of the RSC or ACC (*P < 0.05, Steiger’s z-test). Data are presented as the mean ± SEM.
Mentions: To identify correlations between the OFC freezing levels and the amyloid plaque burden, the plaque area was quantified at the AI, BLA, RSC, and ACC of all groups (Fig. 4A,B; Supplementary Fig. S6A,B). No accumulation was observed in Wt-3, Wt-7, and Wt-11 mice. Although amyloid plaques were not observed in Tg-3 mice, these structures appeared in Tg-7 mice and were significantly increased in Tg-11 mice at the AI (Fig. 4C; ***P < 0.001). In the BLA, there was no difference between Tg-3 and Tg-7 mice, but Tg-11 mice showed a significantly higher plaque burden compared with Tg-3 or Tg-7 animals (Fig. 4D; ***P < 0.001). The RSC and ACC also showed significant increases in plaque burden with increasing age of the Tg mice (Supplementary Fig. S6C,D). The plaque burden in the AI showed the highest correlation with OFC freezing levels (Fig. 4E; rs = 0.729, P < 0.0001). Other regions also showed significant correlations with OFC freezing levels (Fig. 4F; P < 0.0001; Supplementary Fig. S6E,F; P < 0.001), but the correlation coefficient of the AI was significantly higher than that of the RSC and ACC (Fig. 4G; *P < 0.05).

View Article: PubMed Central - PubMed

ABSTRACT

Emotional contagion, a primitive form of empathy, is heightened in patients with Alzheimer&rsquo;s disease (AD); however, the mechanism underlying this attribute has not been thoroughly elucidated. In this study, observational fear conditioning was performed to measure emotional contagion levels in a mouse model of AD. Simultaneous recording of local field potentials in the bilateral anterior insula, basolateral amygdala, anterior cingulate cortex, and retrosplenial cortex was also conducted to investigate related brain network changes. Consistent with the results obtained with AD patients, 11-month-old AD model mice exhibited significantly higher freezing levels in observational fear conditioning, indicating elevated emotional contagion compared to age-matched wild-type mice. Furthermore, the left anterior insula and right basolateral amygdala of 11-months-old AD model mice indicated sustained increases in synchronization when they observed the suffering of conspecifics. These changes did not appear in other age groups or wild-type controls. Additionally, the amyloid plaque burden within the anterior insula was significantly correlated with the freezing levels in observational fear conditioning. Taken together, this study reveals increased and sustained network synchrony between the anterior insula and basolateral amygdala, which comprise a salience network in humans, as a potential mechanism for elevated emotional contagion in a mouse model of AD.

No MeSH data available.


Related in: MedlinePlus