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- Impact of Peripheral Inflammation on the Susceptibility to Neurodegenerative DiseasesPublication . Vale, Ana Margarida Gonçalves Candeias do; Bernardino, Liliana Inácio; Cristóvão, Ana ClaraLipopolysaccharide (LPS) is an inflammatory agent widely used to induce peripheral inflammatory responses in animal models. When administered at low concentrations and over a short time interval, it has the ability to induce neuroprotection in animal models of Alzheimer’s Disease and stroke. This neuroprotective effect is due to the activation of the peripheral immune system and subsequently activation and induction of innate immune memory in microglial cells. Thus, the main objective of this work was to understand the effects of LPS and histamine, a biogenic amine also involved in peripheral inflammatory reactions, in the ability to induce innate immune memory and, consequently, to promote neuroprotection of dopaminergic neurons in an animal model of Parkinson’s Disease (PD). For this, C57BL/6J mice were subjected to intraperitoneal administration with LPS or histamine and, after 3 weeks, were exposed to intrastriatal injury with 6-hydroxydopamine (6-OHDA) to mimetize PD. The inflammatory response was evaluated by the expression of proinflammatory cytokines (TNF-a and IL-1ß) and anti-inflammatory cytokines (IL-10) in the blood, and by the expression of the ionised calcium binding adapter molecule 1 (Iba-1), a cell marker of microglia and macrophage cells, in the brain. To evaluate dopaminergic survival and motor behavior, immunohistochemistry for tyrosine hydroxylase (TH) and apomorphine test were use, respectively. The results suggest that LPS and histamine induce activation of the peripheral inflammatory response with consequent activation of microglia, triggering innate immune memory. In the long term, it is verified that these inflammatory stimuli protect dopaminergic neurons in a PD model, as well as motor recovery, resulting in a new mechanism of prevention and cellular and functional improvement of PD.