title: Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.
abstract: Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25μg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors.forename: Qi-Gang
authors.initials: QG
authors.lastname: Yang
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Tong
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China; Department of Neurology, the Affiliated Chaohu Hospital of Anhui Medical University, and the Center of Anhui Province in Psychologic Medicine, Chaohu, Hefei 238000, Anhui Province, PR China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China; Department of Neurology, the Affiliated Chaohu Hospital of Anhui Medical University, and the Center of Anhui Province in Psychologic Medicine, Chaohu, Hefei 238000, Anhui Province, PR China; Department of Neurology, the First People's Hospital of Chenzhou, Chenzhou 423000, Hunan Province, PR China. Electronic address: doctorcgh@163.com.
authors.forename: Gui-Hai
authors.initials: GH
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000209:etiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology*; D050863:Synaptotagmin I / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: D006657:Histones; D008070:Lipopolysaccharides; D050863:Synaptotagmin I; D050827:Syntaxin 1
keywords: Aging; Histone acetylation; Lipopolysaccharide; Memory; Mice