Abstract
In developing youth, allergic asthma is the most common chronic condition, with 9%-10% of youth affected. Asthma onset during childhood and adolescence is further associated with other health issues, particularly psychiatric conditions. To understand causal mechanisms by which developmental asthma may lead to altered behavior, brain and health trajectories, we developed a mouse model of developmental allergic asthma. In the current study, we tested for potential long-term effects of developmental asthma on adult lung function and behavior and brain gene expression associated with emotion and stress regulation. We manipulated airway inflammation (AI) and methacholine (MCH)-induced bronchospasm (resulting in labored breathing, LB) in young male and female BALB/cJ mice and measured adult outcomes 3 months after final asthma manipulations. Results indicated that allergen exposure, used to cause AI, and which ended on post-natal day 56 (P56), led to persistent lung AI, mucus buildup and gene expression related to allergic asthma 3 months after final allergen exposure. In addition, at this same age, early allergen exposure led to altered brain gene expression related to stress regulation (prefrontal corticotropin releasing hormone receptor 1, Crhr1 and hippocampal glucocorticoid receptor, GR) and serotonin function (brainstem serotonin transporter, SERT). On the other hand, LB events during development led to altered anxiety-related behavior. Importantly, sex and pre-asthma fear-related behavior (ultrasonic vocalization, USV rates) modulated these adult outcomes. Asthma that develops during childhood/adolescence may have long-term impacts on emotion and stress regulation mechanisms, and these influences may be moderated by sex and pre-asthma temperament.
| Original language | English (US) |
|---|---|
| Article number | 188 |
| Journal | Frontiers in Behavioral Neuroscience |
| Volume | 12 |
| DOIs | |
| State | Published - Aug 30 2018 |
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All Science Journal Classification (ASJC) codes
- Neuropsychology and Physiological Psychology
- Cognitive Neuroscience
- Behavioral Neuroscience
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Asthma induction during development and adult lung function, behavior and brain gene expression. / Caulfield, Jasmine I.; Caruso, Michael J.; Bourne, Rebecca A.; Chirichella, Nicole R.; Klein, Laura; Craig, Timothy; Bonneau, Robert H.; August, Avery; Cavigelli, Sonia Angele.
In: Frontiers in Behavioral Neuroscience, Vol. 12, 188, 30.08.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Asthma induction during development and adult lung function, behavior and brain gene expression
AU - Caulfield, Jasmine I.
AU - Caruso, Michael J.
AU - Bourne, Rebecca A.
AU - Chirichella, Nicole R.
AU - Klein, Laura
AU - Craig, Timothy
AU - Bonneau, Robert H.
AU - August, Avery
AU - Cavigelli, Sonia Angele
PY - 2018/8/30
Y1 - 2018/8/30
N2 - In developing youth, allergic asthma is the most common chronic condition, with 9%-10% of youth affected. Asthma onset during childhood and adolescence is further associated with other health issues, particularly psychiatric conditions. To understand causal mechanisms by which developmental asthma may lead to altered behavior, brain and health trajectories, we developed a mouse model of developmental allergic asthma. In the current study, we tested for potential long-term effects of developmental asthma on adult lung function and behavior and brain gene expression associated with emotion and stress regulation. We manipulated airway inflammation (AI) and methacholine (MCH)-induced bronchospasm (resulting in labored breathing, LB) in young male and female BALB/cJ mice and measured adult outcomes 3 months after final asthma manipulations. Results indicated that allergen exposure, used to cause AI, and which ended on post-natal day 56 (P56), led to persistent lung AI, mucus buildup and gene expression related to allergic asthma 3 months after final allergen exposure. In addition, at this same age, early allergen exposure led to altered brain gene expression related to stress regulation (prefrontal corticotropin releasing hormone receptor 1, Crhr1 and hippocampal glucocorticoid receptor, GR) and serotonin function (brainstem serotonin transporter, SERT). On the other hand, LB events during development led to altered anxiety-related behavior. Importantly, sex and pre-asthma fear-related behavior (ultrasonic vocalization, USV rates) modulated these adult outcomes. Asthma that develops during childhood/adolescence may have long-term impacts on emotion and stress regulation mechanisms, and these influences may be moderated by sex and pre-asthma temperament.
AB - In developing youth, allergic asthma is the most common chronic condition, with 9%-10% of youth affected. Asthma onset during childhood and adolescence is further associated with other health issues, particularly psychiatric conditions. To understand causal mechanisms by which developmental asthma may lead to altered behavior, brain and health trajectories, we developed a mouse model of developmental allergic asthma. In the current study, we tested for potential long-term effects of developmental asthma on adult lung function and behavior and brain gene expression associated with emotion and stress regulation. We manipulated airway inflammation (AI) and methacholine (MCH)-induced bronchospasm (resulting in labored breathing, LB) in young male and female BALB/cJ mice and measured adult outcomes 3 months after final asthma manipulations. Results indicated that allergen exposure, used to cause AI, and which ended on post-natal day 56 (P56), led to persistent lung AI, mucus buildup and gene expression related to allergic asthma 3 months after final allergen exposure. In addition, at this same age, early allergen exposure led to altered brain gene expression related to stress regulation (prefrontal corticotropin releasing hormone receptor 1, Crhr1 and hippocampal glucocorticoid receptor, GR) and serotonin function (brainstem serotonin transporter, SERT). On the other hand, LB events during development led to altered anxiety-related behavior. Importantly, sex and pre-asthma fear-related behavior (ultrasonic vocalization, USV rates) modulated these adult outcomes. Asthma that develops during childhood/adolescence may have long-term impacts on emotion and stress regulation mechanisms, and these influences may be moderated by sex and pre-asthma temperament.
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U2 - 10.3389/fnbeh.2018.00188
DO - 10.3389/fnbeh.2018.00188
M3 - Article
VL - 12
JO - Frontiers in Behavioral Neuroscience
JF - Frontiers in Behavioral Neuroscience
SN - 1662-5153
M1 - 188
ER -