Prevotella nigrescens exacerbates periodontal inflammation and impairs cognitive function in mice

doi:10.12122/j.issn.1673-4254.2025.03.02

Abstract

Abstract:

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. Methods Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. Results After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. Conclusion Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

Key words: Prevotella nigrescens, oral bacteria, periodontitis, cognitive impairment, behavioral changes

Qi CHEN, Tiantian XIA, Yongqiang ZHOU, Mingyang CHANG, Nan HU, Yanmei YANG, Zhong LI, Yue GAO, Bin GU. Prevotella nigrescens exacerbates periodontal inflammation and impairs cognitive function in mice[J]. Journal of Southern Medical University, 2025, 45(3): 453-460.

Figures/Tables 6

Fig.1 Flowchart of the experiment.

Fig.2 HE staining of periodontal histological sections of the mice at 6 weeks after modeling (scale bar=200 μm for upper and lower panels; P: Periodontitis).

Fig.3 Establishment of a mouse periodontitis model and Micro-CT scan and 3D reconstruction analysis. A: Periodontitis in a mouse model. B: Micro-CT scan and 3D reconstruction for measurement of positional markings. C: Analysis of periodontal bone defects by Micro-CT and the distance from the enamel bone boundary to the top of the alveolar ridge (CAJ-ABC). **P<0.01 vs control group. P: Periodontitis.

Fig.4 Body weight changes during the observation period in periodontitis mice. **P<0.01, ***P<0.001 vs control group; #P<0.05 vs P group.

Fig.5 Learning and memory functions of mice with periodontitis modeled using the two methods. A: Open field test. B: representative tracking images of movement over 5 min, total distance covered, percent distance covered on the central grid, percent time spent on the central grid. C: New object recognition test (NORT). D: Percentage of distance covered around a new object, discrimination index (DI), percentage of times a new object was explored. E: Morris water maze test (MWM). F: Platform finding latency 5 days prior to training. G: Percentage of platform finding latency, number of platform traversals, time spent in target quadrant activity, and percentage of distance traveled in target quadrant activity. (*P<0.05,**P<0.01, ***P<0.001, ****P<0.0001 vs control group; #P<0.05, ##P<0.01, ####P<0.0001 vs P group. P: Periodontitis group; P+Pn: Periodontitis + Pn bacteria group).

Fig.6 Histological observations for assessing morphological and functional changes of hippocampal neurons in the brain of the mouse models. A: HE staining of the hippocampal region of the mice in each group (scale bar=200 μm) and the normal neuron numbers in the CA3 region. B: Nissl staining of the hippocampal region of the mice in each group (scale bar=200 μm) and Nissl-positive neuron numbers in the CA3 region. *P<0.05 vs control group; #P<0.05 vs P group.

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