{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:05:09Z","timestamp":1780909509511,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tic disorder (TD) is a neurodevelopmental condition for which pharmacological treatments are limited and are frequently associated with side effects. Jingxin Zhidong formula (JXZDF) offers a potential alternative therapy; however, its mechanism of action has not been fully elucidated. This study investigated the therapeutic effects of JXZDF on TD and explored underlying mechanisms involving neurotransmitter regulation and microglial I\u03baB kinase\/nuclear factor\u2010\u03baB (IKK\/NF\u2010\u03baB) signaling, a pathway implicated in both inflammatory activation and metabolic reprogramming.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A TD rat model was established using 3,3'\u2010iminodipropionitrile (IDPN). Rats were treated with low\u2010, medium\u2010, or high\u2010dose JXZDF or aripiprazole for three weeks, after which behavioral scores were assessed. Histology, immunohistochemistry, quantitative reverse transcription\u2010polymerase chain reaction, western blotting (WB), and enzyme\u2010linked immunosorbent assay (ELISA) analyses of striatal tissue were performed to evaluate neuronal morphology, neurotransmitter receptor expression (N\u2010methyl\u2010D\u2010aspartate receptor subunit 1 [NMDAR1], glutamate receptor 1 [GRIA1], gamma\u2010aminobutyric acid type A receptor \u03b11 subunit [GABAAR\u03b11], and gamma\u2010aminobutyric acid type A receptor \u03b22 subunit [GABAA\u03b22]), as well as glutamate and GABA levels. The IKK\/NF\u2010\u03baB pathway was examined both in vivo and in lipopolysaccharide\u2010stimulated BV\u20102 microglial cells using WB, immunofluorescence, and ELISA, with the IKK\u03b2 inhibitor IMD\u20100354 used for mechanistic validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>JXZDF treatment significantly reduced abnormal behavioral scores in the TD rat model in a dose\u2010dependent manner. Treatment ameliorated striatal neuronal damage and corrected the neurotransmitter imbalance by specifically reducing glutamate and increasing the expression of excitatory receptors (NMDAR1, \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptors [AMPAR], and glutamate receptor subunit 1 [GluA1]), while increasing GABA and inhibitory receptor expression (GABAAR\u03b11 and GABAA\u03b22). JXZDF also suppressed IKK\/NF\u2010\u03baB pathway activation in the striatum of TD rats and in LPS\u2010activated BV\u20102 cells, as evidenced by reduced I\u03baB\u03b1 and NF\u2010\u03baB p65 phosphorylation, inhibited NF\u2010\u03baB p65 nuclear translocation, and decreased pro\u2010inflammatory cytokine (interleukin\u20106 [IL\u20106], tumor necrosis factor\u2010alpha [TNF\u2010\u03b1]) secretion. The anti\u2010inflammatory and neuroprotective effects of JXZDF were reversed by co\u2010treatment with IMD\u20100354.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>JXZDF alleviated tic\u2010like behaviors in a TD rat model by restoring striatal excitatory\u2010inhibitory neurotransmitter balance and inhibiting microglial\u2010mediated neuroinflammation. Its therapeutic effect was at least partially mediated by suppression of IKK\/NF\u2010\u03baB. These findings provide a pharmacological basis for the clinical application of JXZDF in TD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71361","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T16:30:57Z","timestamp":1774801857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Jingxin Zhidong Formula Alleviates Tic Disorder via Modulation of Microglial IKK\/NF\u2010\u03baB Signaling and Striatal Neurotransmitter Homeostasis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3831-2646","authenticated-orcid":false,"given":"Fei","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Experimental Research Center China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenghui","family":"Niu","sequence":"additional","affiliation":[{"name":"Experimental Research Center China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0715-3830","authenticated-orcid":false,"given":"Chengkui","family":"Xiu","sequence":"additional","affiliation":[{"name":"Experimental Research Center China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32832ec5ea"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010020\u201000914\u20106"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1691717"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64012-3.00008-3"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2025.102660"},{"key":"e_1_2_13_7_1","first-page":"221","article-title":"A New Animal Model for Tourette Syndrome","volume":"35","author":"Diamond B. 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