Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice

Int J Dev Neurosci. 2016 Dec:55:56-65. doi: 10.1016/j.ijdevneu.2016.09.010. Epub 2016 Sep 22.

Abstract

Background: Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count.

Methods: We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression.

Results: AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers.

Conclusions: AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model.

Keywords: Adverse early life environment; Hippocampus; Microglia; Neural stem cells; Neurons.

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Antigens, CD / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cells, Cultured
  • Diet, Western
  • Disease Models, Animal
  • Environment*
  • Female
  • Flow Cytometry
  • Hippocampus / growth & development
  • Hippocampus / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microglia / pathology*
  • Nestin / metabolism
  • Neural Stem Cells / physiology*
  • Phosphopyruvate Hydratase / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diet therapy
  • Prenatal Exposure Delayed Effects / pathology*
  • RNA, Messenger / metabolism
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism

Substances

  • Aif1 protein, mouse
  • Antigens, CD
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Nestin
  • RNA, Messenger
  • Toll-Like Receptor 9
  • Phosphopyruvate Hydratase