RESUMO
We studied the effect of soluble factors derived from human macrophages polarized to M2 phenotype under conditions of serum deprivation (M2-SF) on behavioral pattern and cytokine production in various brain structures in mice with modeled stress-induced depression. Intranasal administration of M2-SF for 7 days led to stimulation of locomotor and exploratory activities and a decrease in emotional reactivity in the open-field test as well as reduction in depression-like behavior in Porsolt forced swimming test and a decrease in anxiety and anhedonia. Correction of depression-like behavior was accompanied by down-regulation of proinflammatory cytokines (IL-1ß, IL-6, TNFα, and IFNγ) in pathogenetically important brain structures (striatum, hippocampus, and frontal cortex). These data indicate that the antidepressant potential of M2 type macrophages can be mediated by the anti-inflammatory effects of M2-SF.
Assuntos
Antidepressivos , Depressão , Animais , Antidepressivos/farmacologia , Encéfalo/metabolismo , Citocinas/metabolismo , Depressão/tratamento farmacológico , Macrófagos/metabolismo , CamundongosRESUMO
Macrophages play the key role in the regulation of neuroregeneration. For evaluation of the neuroregenerative potential of M2 macrophages, we studied the effect of macrophages polarized with IL-4 (M2a (IL-4)) and by efferocytosis under conditions of serum deprivation (LS, Low Serum; M2(LS)) on proliferative activity and apoptosis of SH-SY5Y cells under conditions of deficiency of growth/serum factors. Conditioned media of both M2(LS) and M2a(IL-4) stimulated proliferation of SH-SY5Y cells. Moreover, soluble factors of M2(LS) and M2a(IL-4) reduced the degree of early apoptosis of SH-SY5Y cells and the protective effect of M2(LS) was observed at earlier terms of culturing. Our findings suggest that M2 macrophages have high neuroregenerative potential that is mediated through soluble factors and manifests itself both in stimulation of proliferation and inhibition of apoptosis of SH-SY5Y cells.