title: Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.
abstract: Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure.
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. ypang@umc.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pang
authors.affiliation: School of Medicine, Fu Jen Catholic University, Xinzhuang Dist, New Taipei City 24205, Taiwan. 068154@mail.fju.edu.tw.
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. zzhu@umc.edu.
authors.forename: Hobart
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. sunnylele@hotmail.com.
authors.forename: Juying
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. cfwright@umc.edu.
authors.forename: Camilla F
authors.initials: CF
authors.lastname: Wright
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. tkjones@umc.edu.
authors.forename: Tembra K
authors.initials: TK
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. samamoon@umc.edu.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Mamoon
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. abhatt@umc.edu.
authors.forename: Abhay J
authors.initials: AJ
authors.lastname: Bhatt
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. zcai@umc.edu.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. lwfan@umc.edu.
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000276:immunology; D042967:Electron Transport Complex I / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008124:Locomotion; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011596:Psychomotor Disorders / Q000276:immunology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D042967:Electron Transport Complex I