title: VIP enhances phagocytosis of fibrillar beta-amyloid by microglia and attenuates amyloid deposition in the brain of APP/PS1 mice.
abstract: Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities. It has been shown to inhibit Amyloid beta (Aβ)-induced neurodegeneration by indirectly suppressing the production and release of a variety of inflammatory and neurotoxic factors by activated microglia. We demonstrated that VIP markedly increased microglial phagocytosis of fibrillar Aβ42 and that this enhanced phagocytotic activity depended on activation of the Protein kinase C (PKC) signaling pathway. In addition, VIP suppressed the release of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) from microglia activated by combined treatment with fibrillar Aβ42 and low dose interferon-γ (IFN-γ). We utilized an adenovirus-mediated gene delivery method to overexpress VIP constitutively in the hippocampus of APPswPS1 transgenic mice. The Aβ load was significantly reduced in the hippocampus of this animal model of Alzheimer's disease, possibly due to the accumulation and activation of cd11b-immunoactive microglial cells. The modulation of microglial activation, phagocytosis, and secretion by VIP is a promising therapeutic option for the treatment of Alzheimer's disease (AD).
authors.affiliation: Department of Medical Genetics, Third Military Medical University, ChongQing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Jia-xiang
authors.initials: JX
authors.lastname: Xiong
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide