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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

Both neonatal no‐sevo‐ and sevo‐treated mice showed no impairment in communication behavior based on olfactory habituation/dishabituation. Mice were able to habituate to the same scent when presented three consecutive times. This was shown by a significant decrease in the time spent sniffing from the first to the last presentation of the same scent. Repeated measure two‐way ANOVA resulted in F(2, 66) = 30, P < 0.0001 for water; F(2, 66) = 40, P < 0.0001 for almond; F(2, 66) = 40, P < 0.0001 for orange; and F(2, 66) = 40, P < 0.0001 for social 1 and F(2, 66) = 5, P < 0.01 for social 2. There was no treatment difference on nonsocial and social 1 odor habituation. These mice were also able to dishabituate from old scents when new scents were presented. This was shown by a significant increase in every transition between the last presentation of the old scent to the first presentation of the new scent. A two‐way ANOVA resulted in F(1, 66) = 31, P < 0.0001 for transition from water to almond; F(1, 66) = 20, P < 0.0001 for transition from almond to orange; F(1, 66) = 127, P < 0.0001 for transition from orange to social 1; and F(1, 66) = 14, P < 0.001 for transition from social 1 to social 2. There was no treatment difference on odor dishabituation. However, sevo‐treated mice were observed to have a social interaction abnormality in this paradigm. There was a treatment difference on social 2 odor habituation, in which a repeated measure two‐way ANOVA resulted in F(1, 66) = 4, P = 0.05 for treatment. Asterisk (*) denotes P = 0.05 for treatment effect on social 2 odors: mouse 2‐1, 2‐2, and 2‐3 (N = 18 for no sevo; N = 17 for sevo).
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brb3514-fig-0007: Both neonatal no‐sevo‐ and sevo‐treated mice showed no impairment in communication behavior based on olfactory habituation/dishabituation. Mice were able to habituate to the same scent when presented three consecutive times. This was shown by a significant decrease in the time spent sniffing from the first to the last presentation of the same scent. Repeated measure two‐way ANOVA resulted in F(2, 66) = 30, P < 0.0001 for water; F(2, 66) = 40, P < 0.0001 for almond; F(2, 66) = 40, P < 0.0001 for orange; and F(2, 66) = 40, P < 0.0001 for social 1 and F(2, 66) = 5, P < 0.01 for social 2. There was no treatment difference on nonsocial and social 1 odor habituation. These mice were also able to dishabituate from old scents when new scents were presented. This was shown by a significant increase in every transition between the last presentation of the old scent to the first presentation of the new scent. A two‐way ANOVA resulted in F(1, 66) = 31, P < 0.0001 for transition from water to almond; F(1, 66) = 20, P < 0.0001 for transition from almond to orange; F(1, 66) = 127, P < 0.0001 for transition from orange to social 1; and F(1, 66) = 14, P < 0.001 for transition from social 1 to social 2. There was no treatment difference on odor dishabituation. However, sevo‐treated mice were observed to have a social interaction abnormality in this paradigm. There was a treatment difference on social 2 odor habituation, in which a repeated measure two‐way ANOVA resulted in F(1, 66) = 4, P = 0.05 for treatment. Asterisk (*) denotes P = 0.05 for treatment effect on social 2 odors: mouse 2‐1, 2‐2, and 2‐3 (N = 18 for no sevo; N = 17 for sevo).

Mentions: Mice were presented with three different nonsocial odors and two different social odors on cotton swabs. Both the sevo‐ and no‐sevo–treated groups were able to habituate to the same odor when it was presented three consecutive times. This is indicated by a significant decrease in time spent sniffing the cotton swabs of the same odor from the first to the third presentation (Fig. 7; repeated measure two‐way ANOVA, P < 0.0001 for time spent sniffing cotton swabs from the first to the third presentation of the odors: water, almond, orange, and social 1; repeated measure two‐way ANOVA, P < 0.01 for time spent sniffing cotton swabs from the first to the third presentation of the odor, social 2). There was no treatment difference on habituation for nonsocial and social 1 odors. Presentation of new odors elicited increased interest such that both groups of mice were able to dishabituate from the old scent to the new scent. This is indicated by a significant increase in time spent sniffing the cotton swab from the last presentation of the old odor to the first presentation of the new odor (two‐way ANOVA, P < 0.01–0.0001 for change of odor: transition from an old to a new odor). While both groups of mice showed similar behavior in olfactory cue habituation/dishabituation in nonsocial odors, we noticed a difference in their behavior toward the social odors. The sevo‐treated mice showed significantly less interest in sniffing compared to no‐sevo–treated mice when novel mouse 2 odors were presented (repeated measure two‐way ANOVA, P = 0.05 for treatment). These data further validate a deficiency in social interaction behavior in P7 sevo‐treated mice, an observation that has been recapitulated in two other behavioral paradigms in this current study: reciprocal social and three‐chamber social interaction.


Early ‐ life single ‐ episode sevoflurane exposure impairs social behavior and cognition later in life
Both neonatal no‐sevo‐ and sevo‐treated mice showed no impairment in communication behavior based on olfactory habituation/dishabituation. Mice were able to habituate to the same scent when presented three consecutive times. This was shown by a significant decrease in the time spent sniffing from the first to the last presentation of the same scent. Repeated measure two‐way ANOVA resulted in F(2, 66) = 30, P < 0.0001 for water; F(2, 66) = 40, P < 0.0001 for almond; F(2, 66) = 40, P < 0.0001 for orange; and F(2, 66) = 40, P < 0.0001 for social 1 and F(2, 66) = 5, P < 0.01 for social 2. There was no treatment difference on nonsocial and social 1 odor habituation. These mice were also able to dishabituate from old scents when new scents were presented. This was shown by a significant increase in every transition between the last presentation of the old scent to the first presentation of the new scent. A two‐way ANOVA resulted in F(1, 66) = 31, P < 0.0001 for transition from water to almond; F(1, 66) = 20, P < 0.0001 for transition from almond to orange; F(1, 66) = 127, P < 0.0001 for transition from orange to social 1; and F(1, 66) = 14, P < 0.001 for transition from social 1 to social 2. There was no treatment difference on odor dishabituation. However, sevo‐treated mice were observed to have a social interaction abnormality in this paradigm. There was a treatment difference on social 2 odor habituation, in which a repeated measure two‐way ANOVA resulted in F(1, 66) = 4, P = 0.05 for treatment. Asterisk (*) denotes P = 0.05 for treatment effect on social 2 odors: mouse 2‐1, 2‐2, and 2‐3 (N = 18 for no sevo; N = 17 for sevo).
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brb3514-fig-0007: Both neonatal no‐sevo‐ and sevo‐treated mice showed no impairment in communication behavior based on olfactory habituation/dishabituation. Mice were able to habituate to the same scent when presented three consecutive times. This was shown by a significant decrease in the time spent sniffing from the first to the last presentation of the same scent. Repeated measure two‐way ANOVA resulted in F(2, 66) = 30, P < 0.0001 for water; F(2, 66) = 40, P < 0.0001 for almond; F(2, 66) = 40, P < 0.0001 for orange; and F(2, 66) = 40, P < 0.0001 for social 1 and F(2, 66) = 5, P < 0.01 for social 2. There was no treatment difference on nonsocial and social 1 odor habituation. These mice were also able to dishabituate from old scents when new scents were presented. This was shown by a significant increase in every transition between the last presentation of the old scent to the first presentation of the new scent. A two‐way ANOVA resulted in F(1, 66) = 31, P < 0.0001 for transition from water to almond; F(1, 66) = 20, P < 0.0001 for transition from almond to orange; F(1, 66) = 127, P < 0.0001 for transition from orange to social 1; and F(1, 66) = 14, P < 0.001 for transition from social 1 to social 2. There was no treatment difference on odor dishabituation. However, sevo‐treated mice were observed to have a social interaction abnormality in this paradigm. There was a treatment difference on social 2 odor habituation, in which a repeated measure two‐way ANOVA resulted in F(1, 66) = 4, P = 0.05 for treatment. Asterisk (*) denotes P = 0.05 for treatment effect on social 2 odors: mouse 2‐1, 2‐2, and 2‐3 (N = 18 for no sevo; N = 17 for sevo).
Mentions: Mice were presented with three different nonsocial odors and two different social odors on cotton swabs. Both the sevo‐ and no‐sevo–treated groups were able to habituate to the same odor when it was presented three consecutive times. This is indicated by a significant decrease in time spent sniffing the cotton swabs of the same odor from the first to the third presentation (Fig. 7; repeated measure two‐way ANOVA, P < 0.0001 for time spent sniffing cotton swabs from the first to the third presentation of the odors: water, almond, orange, and social 1; repeated measure two‐way ANOVA, P < 0.01 for time spent sniffing cotton swabs from the first to the third presentation of the odor, social 2). There was no treatment difference on habituation for nonsocial and social 1 odors. Presentation of new odors elicited increased interest such that both groups of mice were able to dishabituate from the old scent to the new scent. This is indicated by a significant increase in time spent sniffing the cotton swab from the last presentation of the old odor to the first presentation of the new odor (two‐way ANOVA, P < 0.01–0.0001 for change of odor: transition from an old to a new odor). While both groups of mice showed similar behavior in olfactory cue habituation/dishabituation in nonsocial odors, we noticed a difference in their behavior toward the social odors. The sevo‐treated mice showed significantly less interest in sniffing compared to no‐sevo–treated mice when novel mouse 2 odors were presented (repeated measure two‐way ANOVA, P = 0.05 for treatment). These data further validate a deficiency in social interaction behavior in P7 sevo‐treated mice, an observation that has been recapitulated in two other behavioral paradigms in this current study: reciprocal social and three‐chamber social interaction.

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