title: Lipolysaccharide-Induced Neuroinflammation Is Associated with Alzheimer-Like Amyloidogenic Axonal Pathology and Dendritic Degeneration in Rats.
abstract: Chronic neuroinflammation is thought to play an etiological role in Alzheimer's disease (AD), which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatiotemporal link between neuritic and amyloid pathology, with the obligatory enzyme forβ-amyloid (Aβ) production, namelyβ-secretase-1 (BACE1), is overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aβin these genetically modified animals. Here we explored the occurrence of the AD-like axonal and dendritic pathology in adult rat brain affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated the ipsilateral hippocampal lysates in the LPS treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increasedβ-amyloid precursor protein and Aβantibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China ; Department of Nursing in Internal Medicine, School of Nursing, Xiangtan Vocational and Technical College, Xiangtan, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Ai
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China ; Department of Anatomy and Physiology, School of Nursing, Xiangtan Vocational and technical College, Xiangtan, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Dahua
authors.initials: D
authors.lastname: Lu
authors.affiliation: Departments of Physiology, Anatomy and Center for Integrated Research in Cognitive and Neural Sciences, Southern Illinois University Carbondale, Carbondale, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Patrylo
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, USA.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Yan
keywords: Amyloid Pathogenesis; Neuritic Dystrophy; Neurodegeneration; Neuroplasticity; Synaptic Pathology