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Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life

View Article: PubMed Central - PubMed

ABSTRACT

Background: Single‐episode anesthetic exposure is the most prevalent surgery‐related incidence among young children in the United States. Although numerous studies have used animals to model the effects of neonatal anesthetics on behavioral changes later on in life, our understanding of the functional consequences to the developing brain in a comprehensive and clinically relevant manner is unclear.

Methods: The volatile anesthetic, sevoflurane (sevo) was administered to C57BL6 postnatal day 7 (P7) mice in a 40% oxygen and 60% nitrogen gas mixture. In order to examine the effects of sevo alone on the developing brain in a clinically relevant manner, mice were exposed to an average of 2.38 ± 0.11% sevo for 2 h. No sevo (control) mice were treated in an identical manner without sevo exposure. Mice were examined for cognition and neuropsychiatric‐like behavioral changes at 1–5 months of age.

Results: Using the active place avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated that P7 sevo‐treated mice showed a deficit in learning and memory both during periadolescence and adulthood. We then employed a battery of neuropsychiatric‐like behavioral tests to examine social interaction, communication, and repetitive behavior. Interestingly, compared to the no‐sevo–treated group, sevo‐treated mice showed significant reductions in the time interacting with a novel mouse (push–crawl and following), time and interaction in a chamber with a novel mouse, and time sniffing a novel social odor.

Conclusions: Our study established that single‐episode, 2‐h sevo treatment during early life impairs cognition later on in life. With this approach, we also observed neuropsychiatric‐like behavior changes such as social interaction deficits in the sevo‐treated mice. This study elucidated the effects of a clinically relevant single‐episode sevo application, given during the neonatal period, on neurodevelopmental behavioral changes later on in life.

No MeSH data available.


Related in: MedlinePlus

Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by three‐chamber social interaction. (A) A three‐chamber apparatus was used to examine social interaction as shown in the photograph. The apparatus is divided into an object chamber (left), a center chamber (center), and a novel mouse chamber (right). The doors on both the left and the right side of the center chamber are opened to allow the subject mouse to travel freely in between all three chambers. (B) The no sevo group spent significantly more time in the novel target mouse chamber compared to the object chamber, while the sevo group showed no such preference. Both groups of mice showed the least preference for the center chamber in which there was no novel target mouse or object present. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 81) = 0, P > 0.05 for treatment; F(2, 81) = 46.3, P < 0.0001 for chamber; F(2, 81) = 2.9, P > 0.05 for interaction between chamber and treatment. Asterisk (***) denotes P < 0.001 for time in mouse versus object chamber for the no sevo group; P < 0.001 for time in mouse versus center and object versus center chamber for both the no sevo and the sevo groups. (C) A similar observation was made for the time the mice spent interacting with the novel target mouse or the novel object (sniffing and nose poking). The no‐sevo–treated mice spent significantly more time interacting with the novel target mouse than the novel object. Such an observation was not present in the sevo‐treated group. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 53) = 1.3, P > 0.05 for treatment; F(1, 53) = 14.6, P < 0.001 for subject/object; F(1, 53) = 1.8, P > 0.05 for interaction between treatment and subject/object. Asterisk (***) denotes P < 0.001 for time spent interacting with subject/object for the no sevo group (N = 16 for no sevo; N = 13 for sevo).
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brb3514-fig-0006: Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by three‐chamber social interaction. (A) A three‐chamber apparatus was used to examine social interaction as shown in the photograph. The apparatus is divided into an object chamber (left), a center chamber (center), and a novel mouse chamber (right). The doors on both the left and the right side of the center chamber are opened to allow the subject mouse to travel freely in between all three chambers. (B) The no sevo group spent significantly more time in the novel target mouse chamber compared to the object chamber, while the sevo group showed no such preference. Both groups of mice showed the least preference for the center chamber in which there was no novel target mouse or object present. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 81) = 0, P > 0.05 for treatment; F(2, 81) = 46.3, P < 0.0001 for chamber; F(2, 81) = 2.9, P > 0.05 for interaction between chamber and treatment. Asterisk (***) denotes P < 0.001 for time in mouse versus object chamber for the no sevo group; P < 0.001 for time in mouse versus center and object versus center chamber for both the no sevo and the sevo groups. (C) A similar observation was made for the time the mice spent interacting with the novel target mouse or the novel object (sniffing and nose poking). The no‐sevo–treated mice spent significantly more time interacting with the novel target mouse than the novel object. Such an observation was not present in the sevo‐treated group. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 53) = 1.3, P > 0.05 for treatment; F(1, 53) = 14.6, P < 0.001 for subject/object; F(1, 53) = 1.8, P > 0.05 for interaction between treatment and subject/object. Asterisk (***) denotes P < 0.001 for time spent interacting with subject/object for the no sevo group (N = 16 for no sevo; N = 13 for sevo).

Mentions: We wanted to further understand whether the two groups of P7‐treated mice would differ in a social behavior paradigm that is self‐directed, without the physical elicitation from the novel target mouse. To address this question, we employed the three‐chamber social interaction paradigm (Nadler et al. 2004; Silverman et al. 2010). In this experimental setup, the subject mouse initiated the social approach, while the target novel mouse was confined under a wire pencil cup on one of the two sides of the three‐chamber apparatus (Fig. 6A). Confining the target novel mouse under the wire pencil cup prevented aggressive interaction between the two unfamiliar mice while providing olfactory, visual, auditory, and tactile contact.


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by three‐chamber social interaction. (A) A three‐chamber apparatus was used to examine social interaction as shown in the photograph. The apparatus is divided into an object chamber (left), a center chamber (center), and a novel mouse chamber (right). The doors on both the left and the right side of the center chamber are opened to allow the subject mouse to travel freely in between all three chambers. (B) The no sevo group spent significantly more time in the novel target mouse chamber compared to the object chamber, while the sevo group showed no such preference. Both groups of mice showed the least preference for the center chamber in which there was no novel target mouse or object present. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 81) = 0, P > 0.05 for treatment; F(2, 81) = 46.3, P < 0.0001 for chamber; F(2, 81) = 2.9, P > 0.05 for interaction between chamber and treatment. Asterisk (***) denotes P < 0.001 for time in mouse versus object chamber for the no sevo group; P < 0.001 for time in mouse versus center and object versus center chamber for both the no sevo and the sevo groups. (C) A similar observation was made for the time the mice spent interacting with the novel target mouse or the novel object (sniffing and nose poking). The no‐sevo–treated mice spent significantly more time interacting with the novel target mouse than the novel object. Such an observation was not present in the sevo‐treated group. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 53) = 1.3, P > 0.05 for treatment; F(1, 53) = 14.6, P < 0.001 for subject/object; F(1, 53) = 1.8, P > 0.05 for interaction between treatment and subject/object. Asterisk (***) denotes P < 0.001 for time spent interacting with subject/object for the no sevo group (N = 16 for no sevo; N = 13 for sevo).
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brb3514-fig-0006: Neonatal sevo‐treated mice had a deficiency in social interaction behaviors as shown by three‐chamber social interaction. (A) A three‐chamber apparatus was used to examine social interaction as shown in the photograph. The apparatus is divided into an object chamber (left), a center chamber (center), and a novel mouse chamber (right). The doors on both the left and the right side of the center chamber are opened to allow the subject mouse to travel freely in between all three chambers. (B) The no sevo group spent significantly more time in the novel target mouse chamber compared to the object chamber, while the sevo group showed no such preference. Both groups of mice showed the least preference for the center chamber in which there was no novel target mouse or object present. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 81) = 0, P > 0.05 for treatment; F(2, 81) = 46.3, P < 0.0001 for chamber; F(2, 81) = 2.9, P > 0.05 for interaction between chamber and treatment. Asterisk (***) denotes P < 0.001 for time in mouse versus object chamber for the no sevo group; P < 0.001 for time in mouse versus center and object versus center chamber for both the no sevo and the sevo groups. (C) A similar observation was made for the time the mice spent interacting with the novel target mouse or the novel object (sniffing and nose poking). The no‐sevo–treated mice spent significantly more time interacting with the novel target mouse than the novel object. Such an observation was not present in the sevo‐treated group. Two‐way ANOVA, followed by Bonferroni posttest were used for statistical analysis, F(1, 53) = 1.3, P > 0.05 for treatment; F(1, 53) = 14.6, P < 0.001 for subject/object; F(1, 53) = 1.8, P > 0.05 for interaction between treatment and subject/object. Asterisk (***) denotes P < 0.001 for time spent interacting with subject/object for the no sevo group (N = 16 for no sevo; N = 13 for sevo).
Mentions: We wanted to further understand whether the two groups of P7‐treated mice would differ in a social behavior paradigm that is self‐directed, without the physical elicitation from the novel target mouse. To address this question, we employed the three‐chamber social interaction paradigm (Nadler et al. 2004; Silverman et al. 2010). In this experimental setup, the subject mouse initiated the social approach, while the target novel mouse was confined under a wire pencil cup on one of the two sides of the three‐chamber apparatus (Fig. 6A). Confining the target novel mouse under the wire pencil cup prevented aggressive interaction between the two unfamiliar mice while providing olfactory, visual, auditory, and tactile contact.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Single&#8208;episode anesthetic exposure is the most prevalent surgery&#8208;related incidence among young children in the United States. Although numerous studies have used animals to model the effects of neonatal anesthetics on behavioral changes later on in life, our understanding of the functional consequences to the developing brain in a comprehensive and clinically relevant manner is unclear.

Methods: The volatile anesthetic, sevoflurane (sevo) was administered to C57BL6 postnatal day 7 (P7) mice in a 40% oxygen and 60% nitrogen gas mixture. In order to examine the effects of sevo alone on the developing brain in a clinically relevant manner, mice were exposed to an average of 2.38&nbsp;&plusmn;&nbsp;0.11% sevo for 2&nbsp;h. No sevo (control) mice were treated in an identical manner without sevo exposure. Mice were examined for cognition and neuropsychiatric&#8208;like behavioral changes at 1&ndash;5&nbsp;months of age.

Results: Using the active place avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated that P7 sevo&#8208;treated mice showed a deficit in learning and memory both during periadolescence and adulthood. We then employed a battery of neuropsychiatric&#8208;like behavioral tests to examine social interaction, communication, and repetitive behavior. Interestingly, compared to the no&#8208;sevo&ndash;treated group, sevo&#8208;treated mice showed significant reductions in the time interacting with a novel mouse (push&ndash;crawl and following), time and interaction in a chamber with a novel mouse, and time sniffing a novel social odor.

Conclusions: Our study established that single&#8208;episode, 2&#8208;h sevo treatment during early life impairs cognition later on in life. With this approach, we also observed neuropsychiatric&#8208;like behavior changes such as social interaction deficits in the sevo&#8208;treated mice. This study elucidated the effects of a clinically relevant single&#8208;episode sevo application, given during the neonatal period, on neurodevelopmental behavioral changes later on in life.

No MeSH data available.


Related in: MedlinePlus