Neuroinflammation linked to neuro- and psychopathology primarily involves induction of innate immune genes expressed in microglia, the brain monocyte-like innate immune cells. We previously found that endotoxin induced or injection of TNFα increased blood and brain TNF α activated microglia and induced brain monocyte chemotactic protein-1(MCP-1) (also known as chemokine (C-C motif) ligand 2 (CCL2)), IL-1β and TNFα mRNA that led to persistent neuroinflammation and a delayed (seven to ten months) loss of substantia nigra tyrosine hydroxylase-positive dopamine neurons [1]. These findings were extended to studies of motor function, which found that seven months after a single endotoxin dose, L-3,4-dihydroxyphenylalanine (L-DOPA) reversible rotorod deficits appeared, with continuing loss of function with age and loss of substantia nigra neurons [2]. Endotoxin (lipopolysaccharide (LPS)) activates innate immune responses through toll-like receptor 4 (TLR4) activation of nuclear factor-kappa B (NF-κB) transcription of proinflammatory gene transcription within microglia and other cells. Microglia and proinflammatory signals include multiple positive loops of autocrine and paracrine amplification that contribute to persistent microglial activation in brain [3]. These findings are consistent with hypotheses that infections early in life
