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- Modulação da inflamação e da neurogénese no hipocampo: desvendar uma nova interação entre a histamina e o lipopolissacarídeoPublication . Antunes, Sandra Raquel Pinto Barata; Bernardino, Liliana InácioHistamine is an endogenous biogenic amine that acts as a neurotransmitter in the Central Nervous System and controls a variety of brain functions. Increasing evidences have demonstrated a dual role of histamine in the modulation of microglial-mediated neuroinflammation, a main pathological feature of several neurodegenerative conditions. Yet, the role of this amine on hippocampus is not yet fully recognized. Therefore, the aim of this work was to evaluate the effects of histamine per se or in the presence of an inflammatory context, namely in hippocampal neuroinflammation and neurogenesis in vivo. To address this aim, mice were injected intraperitoneally with lipopolysaccharide (LPS; 1 or 2 mg/Kg) and further challenged with a stereotaxic injection of histamine in the dentate gyrus (DG) of the hippocampus. First, protein levels of glial reactivity markers, pro-inflammatory factors and neuronal and synaptic function markers were assessed by western blot analysis 4 days after LPS injection. We found that histamine per se increased the expression of glial reactivity markers (ionized calcium binding adaptor molecule 1, Iba1; and glial fibrillary acidic protein, GFAP) while it was able to significantly decrease LPS-induced glial reactivity. Interestingly, histamine per se did not change the expression levels of pro-inflammatory mediators (interleukin-1 beta, IL-1ß; and high mobility group box 1, HMGB1) yet, it was able to counteract the increased expression of the same factors induced by LPS. Histamine was also able to prevent LPS-induced decrease in the expression of both neuronal (cyclic-AMP-response element binding protein, CREB) and postsynaptic (postsynaptic density protein 95, PSD-95) functional markers. Then, the total number of Bromodeoxyuridine (BrdU)/Doublecortin (DCX) and BrdU/Neuronal Nuclei (NeuN)-positive cells were counted in the DG, as a measure of proliferation and survival of newborn mature cells, respectively. We found that histamine per se or upon LPS challenge, increased cell proliferation (BrdU+ cells) and long-term survival of newborn cells (both BrdU+ and BrdU+/DCX+ cells) in the DG niche. Collectively, our results highlight histamine as promising therapeutic agent to treat or improve neuronal conditions associated with hippocampal neuroinflammation and neurodegeneration.