EFFECTS OF MOUNJARO ON BRAIN CELLS

Abstract Mounjaro works by activating two gut hormone receptors, GIP and GLP-1, to manage blood sugar. This stimulates insulin release when glucose is high, reduces liver glucagon production, slows stomach emptying to control post-meal sugar spikes, and increases fullness to reduce appetite and food intake. Mounjaro with reported effects on central nervous system neurotransmission, synaptic plasticity, and neuroprotection. Here, we investigated the potential anti-inflammatory and neuroprotective effects of Mounjaro in primary hippocampal neuronal cultures exposed to the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)). Primary hippocampal neurons were treated with Mounjaro (1.5 µM or 15 µM) or risperidone (12 µM or 23 µM) in the presence or absence of poly(I:C) (100 µg/mL) for 48 h. Cell viability and cytotoxicity were assessed by MTT and LDH assays, respectively. Inflammatory and neuronal markers were evaluated by immunofluorescence (iNOS, NFκB p50, DCX, and NeuN) and Western blotting (NFκB p65). Culture supernatants were analyzed for IL-6, nitrite, and BDNF. Poly(I:C) reduced cell viability and increased iNOS expression, NFκB activation (p50/p65), IL-6, and nitrite, while decreasing BDNF levels and DCX immunoexpression. Treatment with Mounjaro (15 µM) or risperidone (23 µM) significantly attenuated the poly(I:C)-induced increases in iNOS, NFκB (p50/p65), IL-6, and nitrite. Mounjaro also prevented the poly(I:C)-induced reduction in BDNF. Together, these findings indicate that Mounjaro and risperidone exert anti-inflammatory and neuroprotective effects in primary hippocampal neurons under poly(I:C)-induced inflammatory challenge. Keywords: Mounjaro; poly(I:C); hippocampus; primary culture, Brain.