Mouse maternal odontogenic infection with Porphyromonas gingivalis induces cognitive decline in offspring

Eri Ishida; Hisako Furusho; Ting-Yi Renn; Fumie Shiba; Hung-Ming Chang; Hiroshi Oue; Ryuji Terayama; Yukio Ago; Kazuhiro Tsuga; Mutsumi Miyauchi

doi:10.3389/fped.2023.1203894

Mouse maternal odontogenic infection with Porphyromonas gingivalis induces cognitive decline in offspring

Front Pediatr. 2023 Aug 11:11:1203894. doi: 10.3389/fped.2023.1203894. eCollection 2023.

Authors

Affiliations

¹ Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
³ Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Maxillofacial Anatomy and Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁵ Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Abstract

Introduction: Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, causes intrauterine infection/inflammation. Offspring exposed to intrauterine infection/inflammation have an increased risk of neurological disorders, regardless of gestational age. However, the relationship between maternal periodontitis and offspring functional/histological changes in the brain has not yet been elucidated.

Methods: In this study, we used a gestational mouse model to investigate the effects of maternal odontogenic infection of P. gingivalis on offspring behavior and brain tissue.

Results: The step-through passive avoidance test showed that the latency of the acquisition trial was significantly shorter in the P. gingivalis group (p < 0.05), but no difference in spontaneous motor/exploratory parameters by open-field test. P. gingivalis was diffusely distributed throughout the brain, especially in the hippocampus. In the hippocampus and amygdala, the numbers of neuron cells and cyclic adenosine monophosphate response element binding protein-positive cells were significantly reduced (p < 0.05), whereas the number of ionized calcium binding adapter protein 1-positive microglia was significantly increased (p < 0.05). In the hippocampus, the number of glial fibrillary acidic protein-positive astrocytes was also significantly increased (p < 0.05).

Discussion: The offspring of P. gingivalis-infected mothers have reduced cognitive function. Neurodegeneration/neuroinflammation in the hippocampus and amygdala may be caused by P. gingivalis infection, which is maternally transmitted. The importance of eliminating maternal P. gingivalis-odontogenic infection before or during gestation in maintenance healthy brain function in offspring should be addressed in near future.

Keywords: Porphyromonas gingivalis; astrocyte; maternal exposure; microglia; nervous system disease; periodontitis.

Grants and funding

This work was partially supported by Grants-in-Aid for Scientific Research (C) to MM (16K11444) and a Grant-in-Aid for JSPS Fellows to EI (21J14171). The sponsors had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.