Beneficial effects of liraglutide (GLP1 analog) in the hippocampal inflammation.
The brain is very sensitive to metabolic dysfunctions induced by diets high in saturated fatty acids, leading to neuroinflammation. The liraglutide has been found to have neuroprotective effects. However, its neuroprotective action in a model of palmitate-induced neuroinflammation had not yet been evaluated. Mice were intracerebroventricular (ICV) infused with palmitate and received subcutaneous liraglutide. The hippocampal dentate gyrus and CA1 regions were analyzed (morphology and inflammation-related proteins in microglia and astrocyte by confocal microscopy). Also, a real-time PCR was performed to measure the levels of tumor necrosis factor (TNF) alpha and interleukin (IL) 6. Palmitate ICV infusion resulted in pronounced inflammation response in the hippocampus, reactive microgliosis, and astrogliosis, with hypertrophied IBA1 immunoreactive microglia, increased microglial density with ameboid shape, decreased in the number of branches and junctions and increased the major histocompatibility complex (MHC) II expression. Also, we observed in the hippocampus of ICV palmitate infused mice an elevation in the pro-inflammatory cytokine levels TNFalpha and IL6. Liraglutide induced the neuroprotective microglial phenotype, characterized by an increased microglia complexity (enlarged Feret's diameter), an improved number of both cell junctions and processes, and lower circularity, accompanied by a significant reduction in TNFalpha and IL6 expressions. The study provides evidence that liraglutide may be a suitable treatment against the palmitate-induced neuroinflammation, which it is characterized by the reactive microgliosis and astrogliosis, as well as increased pro-inflammatory cytokines, which has been described as one of the primary causes of several pathologies of the central nervous system.
['Barreto-Vianna|Andre R C|ARC|', 'Aguila|Marcia B|MB|', 'Mandarim-de-Lacerda|Carlos A|CA|']
D000818:Animals D056547:CA1 Region, Hippocampal D002135:Calcium-Binding Proteins D018891:Dentate Gyrus D005802:Genes, MHC Class II D005911:Gliosis D006624:Hippocampus D007249:Inflammation D007276:Injections, Intraventricular D015850:Interleukin-6 D000069450:Liraglutide D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008840:Microfilament Proteins D017628:Microglia D018696:Neuroprotective Agents D010168:Palmitates D016133:Polymerase Chain Reaction D014409:Tumor Necrosis Factor-alpha
Saturated fatty acids Neuroinflammation Microglia Hippocampus Intracerebroventricular infusion