Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats

Yu Lung Lin, Sabrina Wang

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)24-34
Number of pages11
JournalBehavioural Brain Research
Volume259
DOIs
StatePublished - Feb 1 2014

Bibliographical note

Funding Information:
We thank Dr. Chien-Ho Wu from China Chemical & Pharmaceutical Co., Ltd for providing us FLX. We thank Dr. Shu-Yi Lin for allowing us to use her Olympus Fluoview FV10i confocal microscope. This study was supported by a research grant to S.W. from the National Science Council of Taiwan (grant number NSC97-2314-B-400-002-MY3 ). Appendix A

Keywords

  • Adult neurogenesis
  • BDNF
  • Depression
  • Maternal infection
  • Prenatal
  • Stress

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