Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.
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.
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address: scohen@mcw.edu.
Susan
S
Cohen
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Xingrao
X
Ke
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Qiuli
Q
Liu
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Qi
Q
Fu
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Amber
A
Majnik
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Robert
R
Lane
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D066273:Diet, Western; D004195:Disease Models, Animal; D004777:Environment; D005260:Female; D005434:Flow Cytometry; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000473:pathology*; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000178:diet therapy / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
C491049:Aif1 protein, mouse; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D064231:Nestin; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9; D010751:Phosphopyruvate Hydratase
Adverse early life environment; Hippocampus; Microglia; Neural stem cells; Neurons