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Neonatal immune activation by lipopolysaccharide causes inadequate emotional responses to novel situations but no changes in anxiety or cognitive behavior in Wistar rats

I. Vojtechova, T. Petrasek, K. Maleninska, H. Brozka, H. Tejkalova, J. Horacek, A. Stuchlik, K. Vales,

. 2018 ; 349 (-) : 42-53. [pub] 20180502

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19000763

Grantová podpora
NV17-30833A MZ0 CEP - Centrální evidence projektů

Infection during the prenatal or neonatal stages of life is considered one of the major risk factors for the development of mental diseases such as schizophrenia or autism. However, the impacts of such an immune challenge on adult behavior are still not clear. In our study, we used a model of early postnatal immune activation by the application of bacterial endotoxin lipopolysaccharide (LPS) to rat pups at a dose of 2 mg/kg from postnatal day (PD) 5 to PD 9. In adulthood, the rats were tested in a battery of tasks probing various aspects of behavior: spontaneous activity (open field test), social behavior (social interactions and female bedding exploration), anxiety (elevated plus maze), cognition (active place avoidance in Carousel) and emotional response (ultrasonic vocalization recording). Moreover, we tested sensitivity to acute challenge with MK-801, a psychotomimetic drug. Our results show that the application of LPS led to increased self-grooming in the female bedding exploration test and inadequate emotional reactions in Carousel maze displayed by ultrasonic vocalizations. However, it did not have serious consequences on exploration, locomotion, social behavior or cognition. Furthermore, exposition to MK-801 did not trigger social or cognitive deficits in the LPS-treated rats. We conclude that the emotional domain is the most sensitive to the changes induced by neonatal immune activation in rats, including a disrupted response to novel and stressful situations in early adulthood (similar to that observed in human patients suffering from schizophrenia or autism), while other aspects of tested behavior remain unaffected.

Citace poskytuje Crossref.org

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$a Vojtechova, Iveta $u First Faculty of Medicine, Charles University, Katerinska 32, 12108, Prague 2, Czech Republic; Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic; National Institute of Mental Health, Topolova 748, 25067, Klecany, Czech Republic. Electronic address: Iveta.Vojtechova@nudz.cz.
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$a Infection during the prenatal or neonatal stages of life is considered one of the major risk factors for the development of mental diseases such as schizophrenia or autism. However, the impacts of such an immune challenge on adult behavior are still not clear. In our study, we used a model of early postnatal immune activation by the application of bacterial endotoxin lipopolysaccharide (LPS) to rat pups at a dose of 2 mg/kg from postnatal day (PD) 5 to PD 9. In adulthood, the rats were tested in a battery of tasks probing various aspects of behavior: spontaneous activity (open field test), social behavior (social interactions and female bedding exploration), anxiety (elevated plus maze), cognition (active place avoidance in Carousel) and emotional response (ultrasonic vocalization recording). Moreover, we tested sensitivity to acute challenge with MK-801, a psychotomimetic drug. Our results show that the application of LPS led to increased self-grooming in the female bedding exploration test and inadequate emotional reactions in Carousel maze displayed by ultrasonic vocalizations. However, it did not have serious consequences on exploration, locomotion, social behavior or cognition. Furthermore, exposition to MK-801 did not trigger social or cognitive deficits in the LPS-treated rats. We conclude that the emotional domain is the most sensitive to the changes induced by neonatal immune activation in rats, including a disrupted response to novel and stressful situations in early adulthood (similar to that observed in human patients suffering from schizophrenia or autism), while other aspects of tested behavior remain unaffected.
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$a Petrasek, Tomas $u Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic; National Institute of Mental Health, Topolova 748, 25067, Klecany, Czech Republic. Electronic address: Tomas.Petrasek@nudz.cz.
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$a Maleninska, Kristyna $u Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic. Electronic address: Kristyna.Maleninska@fgu.cas.cz.
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$a Brozka, Hana $u Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220, Prague 4, Czech Republic. Electronic address: Hana.Brozka@fgu.cas.cz.
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$a Vales, Karel $u National Institute of Mental Health, Topolova 748, 25067, Klecany, Czech Republic. Electronic address: Karel.Vales@nudz.cz.
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