{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:56:12Z","timestamp":1787068572622,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation of China","award":["81771517"],"award-info":[{"award-number":["81771517"]}]},{"name":"National Science Foundation of China","award":["20IRTSTHN030"],"award-info":[{"award-number":["20IRTSTHN030"]}]},{"name":"National Science Foundation of China","award":["212300410013"],"award-info":[{"award-number":["212300410013"]}]},{"name":"Program for Innovative Research Team (in Science and Technology) at the University of Henan Province","award":["81771517"],"award-info":[{"award-number":["81771517"]}]},{"name":"Program for Innovative Research Team (in Science and Technology) at the University of Henan Province","award":["20IRTSTHN030"],"award-info":[{"award-number":["20IRTSTHN030"]}]},{"name":"Program for Innovative Research Team (in Science and Technology) at the University of Henan Province","award":["212300410013"],"award-info":[{"award-number":["212300410013"]}]},{"name":"Natural Science Foundation of Henan Province for Distinguished Young Scholars","award":["81771517"],"award-info":[{"award-number":["81771517"]}]},{"name":"Natural Science Foundation of Henan Province for Distinguished Young Scholars","award":["20IRTSTHN030"],"award-info":[{"award-number":["20IRTSTHN030"]}]},{"name":"Natural Science Foundation of Henan Province for Distinguished Young Scholars","award":["212300410013"],"award-info":[{"award-number":["212300410013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infantile neuronal ceroid lipofuscinosis (INCL), the most severe form of neuronal ceroid lipofuscinoses, is caused by mutations in the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). Typical symptoms of this disease include progressive psychomotor developmental retardation, visual failure, seizures, and premature death. Here, we investigated seizure activity and relevant pathological changes in PPT1 knock-in mice (PPT1 KI). The behavior studies in this study demonstrated that PPT1 KI mice had no significant seizure activity until 7 months of age, and local field potentials also displayed epileptiform activity at the same age. The expression levels of Iba-1 and CD68 demonstrated, by Western blot analysis, the inflammatory cytokine TNF-\u03b1 content measured with enzyme-linked immunosorbent assay, and the number of microglia demonstrated by immunohistochemistry (IHC) were significantly increased at age of 7 months, all of which indicate microglia activation at an age of seizure onset. The increased expression of GFAP were seen at an earlier age of 4 months, and such an increase reached its peak at age of 6 months, indicating that astrocyte activation precedes microglia. The purinergic P2X7 receptor (P2X7R) is an ATP-sensitive ionic channel that is highly expressed in microglia and is fundamental to microglial activation, proliferation, cytokines release and epilepsy. We show that the ATP concentration in hippocampal tissue in PPT1 KI mice was increased using an enhanced ATP assay kit and demonstrated that the antagonist of P2X7R, A-438079, significantly reduced seizures in PPT1 KI mice. In contrast to glial cell activation and proliferation, a significant reduction in synaptic proteins GABAAR was seen in PPT1 KI mice. These results indicate that seizure in PPT1 KI mice may be associated with microglial activation involved in ATP-sensitive P2X7R signaling and impaired inhibitory neurotransmission.<\/jats:p>","DOI":"10.3390\/ijms23105586","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"5586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Seizures in PPT1 Knock-In Mice Are Associated with Inflammatory Activation of Microglia"],"prefix":"10.3390","volume":"23","author":[{"given":"Xusheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyan","family":"Feng","sequence":"additional","affiliation":[{"name":"Henan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1835-7385","authenticated-orcid":false,"given":"Jia","family":"Tong","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengbiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Henan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyong","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/00019052-200304000-00001","article-title":"Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis","volume":"16","author":"Cooper","year":"2003","journal-title":"Curr. 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