title: Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats.
abstract: Major depression is one of the most prevalent mental disorders in the population. In addition to genetic influences, disturbances in fetal nervous system development might be a contributing factor. Maternal infection during pregnancy may affect fetal brain development and consequently lead to neurological and mental disorders. Previously, we used low-dose lipopolysaccharide (LPS) exposure on embryonic day 10.5 to mimic mild maternal infection in rats and found that dopaminergic and serotonergic neurons were reduced in the offspring. The offspring also showed more anxiety-like behavior and an enhanced stress response. In the present study we used forced swim test and chronic mild stress challenge to assess depression-like behaviors in the affected offspring and examined their adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) concentration. Our results showed that prenatally LPS-exposed rats (LPS rats) displayed more depression-like behaviors and had reduced adult neurogenesis and BDNF. The behavioral abnormalities and reduction in adult neurogenesis could be reversed by chronic fluoxetine (FLX) treatment. This study demonstrates that during the critical time of embryonic development LPS exposure can produce long-term behavioral changes and reduction in adult neurogenesis. The findings of enhanced depression-like behaviors, reduced adult neurogenesis, and their responsiveness to chronic antidepressant treatment suggest that prenatal LPS exposure could serve as an animal model of depression.
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC; Graduate Institute of Life Sciences, National Defense Medical Center, 161, Section 6, Minquan E. Road, Neihu District, Taipei 114, Taiwan, ROC.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC; Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 155, Section 2, Li-Nung Street, Beitou District, Taipei 112, Taiwan, ROC; Department of Education and Research, Taipei City Hospital, 145 Zhengzhou Road, Datong District, Taipei 103, Taiwan, ROC. Electronic address: sabrinaw.wang@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D005518:Food Preferences / Q000502:physiology / Q000523:psychology; D006624:Hippocampus / Q000503:physiopathology* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors
chemical_list: D018687:Antidepressive Agents, Second-Generation; D008070:Lipopolysaccharides; D005473:Fluoxetine
keywords: 5-HT; Adult neurogenesis; BDNF; DA; Depression; FLX; LPS; Maternal infection; Prenatal; Stress; brain-derived neurotrophic factor; dopamine; fluoxetine; lipopolysaccharide; polyI:C; polyriboinosinic–polyribocytidylic acid; serotonin