Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation
Abstract Background Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. Howeve...
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doaj-c1403f1e20054dc9b4dc02b2a8bc282e2020-11-24T21:40:53ZengBMCBehavioral and Brain Functions1744-90812019-03-0115111010.1186/s12993-019-0154-2Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestationShuang Ding0Yunqing Hu1Binbin Luo2Yaqi Cai3Keke Hao4Yongfeng Yang5Yan Zhang6Xiujuan Wang7Minli Ding8Hongxing Zhang9Wenqiang Li10Luxian Lv11Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityHenan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityAbstract Background Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. Methods Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague–Dawley rats prenatally challenged with polyriboinosinic–polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1β, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. Results Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. Conclusions Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.http://link.springer.com/article/10.1186/s12993-019-0154-2Maternal immune activationSchizophreniaPoly I:CMicrogliaAstrocyte |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuang Ding Yunqing Hu Binbin Luo Yaqi Cai Keke Hao Yongfeng Yang Yan Zhang Xiujuan Wang Minli Ding Hongxing Zhang Wenqiang Li Luxian Lv |
spellingShingle |
Shuang Ding Yunqing Hu Binbin Luo Yaqi Cai Keke Hao Yongfeng Yang Yan Zhang Xiujuan Wang Minli Ding Hongxing Zhang Wenqiang Li Luxian Lv Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation Behavioral and Brain Functions Maternal immune activation Schizophrenia Poly I:C Microglia Astrocyte |
author_facet |
Shuang Ding Yunqing Hu Binbin Luo Yaqi Cai Keke Hao Yongfeng Yang Yan Zhang Xiujuan Wang Minli Ding Hongxing Zhang Wenqiang Li Luxian Lv |
author_sort |
Shuang Ding |
title |
Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation |
title_short |
Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation |
title_full |
Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation |
title_fullStr |
Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation |
title_full_unstemmed |
Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation |
title_sort |
age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with poly i:c in early gestation |
publisher |
BMC |
series |
Behavioral and Brain Functions |
issn |
1744-9081 |
publishDate |
2019-03-01 |
description |
Abstract Background Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. Methods Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague–Dawley rats prenatally challenged with polyriboinosinic–polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1β, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. Results Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. Conclusions Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia. |
topic |
Maternal immune activation Schizophrenia Poly I:C Microglia Astrocyte |
url |
http://link.springer.com/article/10.1186/s12993-019-0154-2 |
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