The up panels show C圓-Aβ 1–42 associated with microglial cells under the various treatment conditions.

Subsequently, immunofluorescence microscopy examination was performed with a ×10 objective with appropriate filter selection. After 2 hr, these cells were washed and fixed (see Materials and Methods).

C: Mouse primary microglial cells were seeded in twelve-well tissue-culture plates (2×10 5/well) and treated with 500 nM C圓-Aβ 1–42 in the presence or absence of VIP(10 −8 M), LPS (100 ng/ml, as positive control). for cell-associated (right panel) and extracellular (left panel) C圓-Aβ 1–42 using a fluorometer (n = 5 for each condition presented). Cell supernatants and lysates were analyzed. B: Primary microglia cells were stimulated with fibrillar Aβ 1–42 (500 nM) in the absence or presence of different concentrations of VIP(−logM). One-way ANOVA followed by post-hoc comparison showed a significant between-group difference (*P<0.05, **P<0.01 compared with control). Data are represented as the relative fold of mean fluorescence change (mean±SD), calculated as the mean fluorescence for each sample at 37☌ divided by mean fluorescence at 4☌ (n = 5 for each condition presented). The modulation of microglial activation, phagocytosis, and secretion by VIP is a promising therapeutic option for the treatment of Alzheimer's disease (AD).Ī: Cell supernatants and lysates were analyzed for cell-associated (top panel) and extracellular (bottom panel) C圓-Aβ 1–42 using a fluorometer. 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. We utilized an adenovirus-mediated gene delivery method to overexpress VIP constitutively in the hippocampus of APPswPS1 transgenic mice. 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 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. 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. Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities.

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