PMID- 29274031 OWN - NLM STAT- MEDLINE DCOM- 20191002 LR - 20191002 IS - 1557-1904 (Electronic) IS - 1557-1890 (Print) IS - 1557-1890 (Linking) VI - 13 IP - 2 DP - 2018 Jun TI - Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure. PG - 189-203 LID - 10.1007/s11481-017-9774-1 [doi] AB - Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-alpha (TNF-alpha) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain. FAU - Ruggiero, M J AU - Ruggiero MJ AD - Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE, 19716, USA. FAU - Boschen, K E AU - Boschen KE AD - Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE, 19716, USA. FAU - Roth, T L AU - Roth TL AD - Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE, 19716, USA. FAU - Klintsova, A Y AU - Klintsova AY AD - Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE, 19716, USA. klintsova@psych.udel.edu. LA - eng GR - P20 GM103653/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20171222 PL - United States TA - J Neuroimmune Pharmacol JT - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JID - 101256586 RN - 0 (Central Nervous System Depressants) RN - 3K9958V90M (Ethanol) SB - IM MH - Animals MH - Animals, Newborn MH - Central Nervous System Depressants/toxicity MH - Ethanol/*toxicity MH - Female MH - Fetal Alcohol Spectrum Disorders/pathology MH - Hippocampus/*drug effects MH - Male MH - Microglia/*drug effects MH - Neurogenesis/*drug effects MH - Neuroimmunomodulation/drug effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*pathology MH - Rats MH - Rats, Long-Evans MH - Sex Characteristics PMC - PMC5997457 MID - NIHMS971745 OTO - NOTNLM OT - FASD OT - Immune OT - Microglia OT - Postnatal brain OT - Sex differences EDAT- 2017/12/24 06:00 MHDA- 2019/10/03 06:00 PMCR- 2018/06/12 CRDT- 2017/12/24 06:00 PHST- 2017/08/29 00:00 [received] PHST- 2017/12/03 00:00 [accepted] PHST- 2017/12/24 06:00 [pubmed] PHST- 2019/10/03 06:00 [medline] PHST- 2017/12/24 06:00 [entrez] PHST- 2018/06/12 00:00 [pmc-release] AID - 10.1007/s11481-017-9774-1 [pii] AID - 10.1007/s11481-017-9774-1 [doi] PST - ppublish SO - J Neuroimmune Pharmacol. 2018 Jun;13(2):189-203. doi: 10.1007/s11481-017-9774-1. Epub 2017 Dec 22.