Chronic neuroinflammation has a major impact on brain structure and function and has recently been implicated as a causative factor in major psychiatric and neurodegenerative disorders.
Of the different types of proinflammatory mediators which have been identified as a consequence of the activation of the immune system, the cytokines play a crucial role.
The multiple effects of chronic low-grade inflammation initiated by chronic stress and major psychiatric disorders such as depression and schizophrenia on the integrity of the brain’s neural network have been attributed to the neurotoxicity of the proinflammatory cytokines, to the modulation of the biogenic amine neurotransmitters and to the activation of the neurotoxic arm of the tryptophan-kynurenine pathway. In major depression the activation of this pathway by proinflammatory cytokines and glucocorticoids results in the synthesis of the glutamatergic agonist quinolinic acid and neurotoxic kynurenines. These compounds affect the integrity of the neural networks which contribute to neurodegeneration. In addition, the intermediary metabolism of brain glucose is adversely affected as a result of the inflammation-induced dysfunction of insulin.
These changes form a basis for neurodegeneration which, in the middle aged and elderly, could be the prelude for dementia.
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