Tooth Loss Leads to Cognitive Impairment and Mitochondrial Disturbance in Wistar Rats.

BACKGROUND: The link between tooth loss and cognitive impairment has become increasingly significant. Recent findings suggest that mitochondrial alteration in hippocampal neurons may mediate this relationship. OBJECTIVE: This study aimed to explore the mediating role of mitochondria in the relationship between tooth loss and cognitive function in Wistar rats. METHOD: Male Wistar rats (n = 20, 12 weeks old) were randomly divided into tooth extraction (TE) and sham groups. The model was established through upper molar extraction and sham operation respectively. Cognitive evaluations were performed using Morris water maze (MWM) test 8 weeks after the model establishment. Hippocampal neuron morphology was observed. Mitochondrial function was evaluated by ATP level and mitochondrial membrane potential (MMP). Mitophagy assessment involved conducting immunohistochemical and immunofluorescent staining of PTEN-induced kinase 1 (PINK1), Parkin (E3 ubiquitin ligase), translocase of outer mitochondrial membrane 20 (TOMM20), and microtubule-associated protein 1A/1B-light chain 3 (LC3). Additionally, mitophagy protein alterations were analyzed using western blotting. RESULTS: Memory impairment in the TE group was obvious 8 weeks after model establishment. Substantial hippocampal mitochondrial dysfunction was observed in the TE group, evidenced by notably decreased ATP production, decreased MMP level, and abnormal mitochondrial morphology in the hippocampus. Diminished mitophagy was detected by immunofluorescent staining, and further confirmed by immunostaining and western blotting, indicating diminished mitophagy marker levels in PINK1 and Parkin, along with decreased LC3II/I ratios and elevated Sequestosome-1 (SQSTM1/P62) levels, highlighting hippocampal mitophagy deficiency following tooth loss. CONCLUSIONS: Tooth loss leads to mitochondrial disturbance and inhibits PINK1/Parkin-mediated mitophagy in hippocampal neurons, inducing cognitive impairment. CLINICAL RELEVANCE: This study reveals mitochondria may mediate the effect of tooth loss on cognitive function, offering a theoretical basis for the prevention of oral health-associated cognitive decline.