Inflammation-Like Glial Response in Lead-Exposed Immature Rat Brain

Abstract

Numerous studies on lead (Pb) neurotoxicity have indicated this metal to be a dangerous toxin, particularly during developmental stages of higher organisms. Astrocytes are responsible for sequestration of this metal in brain tissue. Activation of astroglia may often lead to loss of the buffering function and contribute to pathological processes. This phenomenon is accompanied by death of neuronal cells and may be connected with inflammatory events arising from the production of a wide range of cytokines and chemokines. The effects of prolonged exposure to Pb upon glial activation are examined in immature rats to investigate this potential proinflammatory effect. When analyzed at the protein level, glial activation is observed after Pb exposure, as reflected by the increased level of glial fibrillary acidic protein and S-100beta proteins in all parts of the brain examined. These changes are associated with elevation of proinflammatory cytokines. Production of interleukin (IL)-1beta and tumor necrosis factor-alpha is observed in hippocampus, and production of IL-6 is seen in forebrain. The expression of fractalkine is observed in both hippocampus and forebrain but inconsiderably in the cerebellum. In parallel with cytokine expression, signs of synaptic damage in hippocampus are seen after Pb exposure, as indicated by decreased levels of the axonal markers synapsin I and synaptophysin. Obtained results indicate chronic glial activation with coexisting inflammatory and neurodegenerative features as a new mechanism of Pb neurotoxicity in immature rat brain.

Toxicity assessment due to sub-chronic exposure to individual and mixtures of four toxic heavy metals

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Effect of occupational exposure to lead on new risk factors for cardiovascular diseases

“…Both tests on animals and humans indicate a relationship between exposure to Pb and the secretion of proinflammatory cytokines 19 20. An increase in cytokine levels in response to exposure to Pb is reflected in the concentration of inflammatory biomarkers, such as CRP and Fb.…”

Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NFκB-independent manner

“…They supply nutrients and oxygen to neurons, insulate one neuron from another, and destroy and remove the carcasses of dead neurons. Recently, a myriad of mounting evidence demonstrated that astrocytes are the type of brain cells that are responsible for sequestration of lead in brain tissue (Strużyńska et al, 2007). As a result, activation of astroglia is one of the modes of action underlying lead neurotoxicity, which may cause loss of the buffering function of astroglia.…”