Fig. 1

Overview of microglia M1 polarization–mediated tic onset. The activation of microglia mainly results from three processes, including increased chemokine ligand 5 (CCL5) levels in the blood, up-regulated immune-related genes, and a lack of histamine (HA). CCL5 in the blood may enter the brain and interact with its receptors, C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 1 (CCR1). The activation of CCR5 promotes neuronal pyroptosis through the CCR5/PKA/CREB/NLRP1 signaling pathway. The activation of CCR1 may result in neurological impairments through the CCR1/TPR1/ERK1/2 signaling pathway. Both of these pathways may cause neuronal impairment and induce the onset of tics. Up-regulated genes related to immunity and inflammation, including C-C motif chemokine ligand 2 (CCL2), intercellular adhesion molecule 1 (ICAM1), heme oxygenase 1 (HMOX1), MYC proto-oncogene (MYC), and suppressor of cytokine signaling 3 (SOCS3), are related to the activation of microglia. The lack of HA may lead to a decrease in the number of IGF-1-positive microglia cells, which have the function of protecting the brain. As a result, HA deficiency increases the susceptibility of microglial cells to inflammation triggered by lipopolysaccharide (LPS). M1-type microglia are known as pro-inflammatory microglia. Microglia M1 hyperpolarization may lead to an increase in inflammatory cytokine levels and sustained neurotoxicity. Striatal dopaminergic neurons are then impaired, which may cause tic disorders, and tics may occur subsequently