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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



Pubmed ID




Scopus ID

2-s2.0-84988731088   20 Citations


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.

Author List

Cohen S, Ke X, Liu Q, Fu Q, Majnik A, Lane R


Susan Cohen MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Analysis of Variance
Animals, Newborn
Antigens, CD
Calcium-Binding Proteins
Cells, Cultured
Diet, Western
Disease Models, Animal
Flow Cytometry
Mice, Inbred C57BL
Microfilament Proteins
Neural Stem Cells
Phosphopyruvate Hydratase
Prenatal Exposure Delayed Effects
RNA, Messenger
Toll-Like Receptor 9