{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:51:49Z","timestamp":1779205909353,"version":"3.51.4"},"reference-count":35,"publisher":"IMR Press","issue":"5","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["19K08018"],"award-info":[{"award-number":["19K08018"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["21K07537"],"award-info":[{"award-number":["21K07537"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["22H02999"],"award-info":[{"award-number":["22H02999"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions. Materials and Methods: Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) injection protocols. The rats received an intraperitoneal injection of saline or Pg-LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg\/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas. Results: The FST immobility time in the Pg-LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the Pg-LPS group compared to the sham group. The peripheral administration of Pg-LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. Pg-LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3. Conclusions: The major result of this study is that a repeated systemic administration of Pg-LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.<\/jats:p>","DOI":"10.31083\/j.jin2205120","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T07:30:47Z","timestamp":1692343847000},"source":"Crossref","is-referenced-by-count":8,"title":["Systemic Administration of Porphyromonas Gingivalis Lipopolysaccharide Induces Glial Activation and Depressive-Like Behavior in Rats"],"prefix":"10.31083","volume":"22","author":[{"given":"Rahman","family":"Mamunur","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Shimane University, 693-8501 Izumo, Japan"},{"name":"Department of Psychiatry, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadayuki","family":"Hashioka","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Asahikawa Medical University, 070-8510 Asahikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhamuddin A.","family":"Azis","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Hasanuddin University, 90245 Kota Makassar, South Sulawesi, Indonesia"},{"name":"Department of Biochemistry, Hasanuddin University, 90245 Kota Makassar, South Sulawesi, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad A.","family":"Jaya","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Hasanuddin University, 90245 Kota Makassar, South Sulawesi, Indonesia"},{"name":"Department of Psychiatry, Faculty of Medicine, Moslem University of Indonesia, 90231 Kota Makassar, South Sulawesi, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sultana J.F.","family":"Jerin","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Shimane University, 693-8501 Izumo, Japan"},{"name":"Department of Psychiatry, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Kimura-Kataoka","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Fujihara","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Inoue","sequence":"first","affiliation":[{"name":"Research and Education Faculty, Medical Sciences Cluster, Health Service Center, Kochi University, 780-8520 Kochi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Inagaki","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Takeshita","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Shimane University, 693-8501 Izumo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref1","unstructured":"World Health Organization. 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