Tooth Loss Induces Memory Impairment and Glial Activation in Young Wild-Type Mice

Abstract

Background: Tooth loss is closely associated with Alzheimer’s disease (AD). Previously, we reported that tooth loss induced memory impairment in amyloid precursor protein knock-in mice by decreasing neuronal activity and synaptic protein levels and increasing glial activation, neuroinflammation, and pyramidal neuronal cell loss without altering amyloid-β levels in the hippocampus. However, the effects of tooth loss in young wild-type mice have not been explored yet. Objective: We investigated the effects of tooth loss on memory impairment, neuronal activity, synaptic protein levels, glial activation, and pyramidal neuronal cell loss in young wild-type mice. Methods: Two-month-old wild-type mice were randomly divided into control and tooth loss groups. In the tooth loss group, maxillary molar teeth on both sides were extracted, whereas no teeth were extracted in the control group. Two months after tooth extraction, we performed a novel object recognition test to evaluate memory function. Glial activation, neuronal activity, synaptic protein levels, and the number of pyramidal neurons were evaluated using immunofluorescence staining, immunohistochemistry, and western blotting. Results: The tooth loss group exhibited memory impairment and decreased neuronal activity and the levels of synaptic proteins in both the hippocampus and cortex. Moreover, tooth loss increased the activation of phosphorylated c-Jun N-terminal kinase (JNK), heat shock protein 90 (HSP90), and glial activation and reduced the number of pyramidal neurons in the hippocampus. Conclusion: Tooth loss in the young wild-type mice will attenuate neuronal activity, decrease synaptic protein levels, and induce pyramidal neuronal loss, and eventually lead to memory impairment.

Periodontitis and Alzheimer’s Disease: Is There a Connection?

“…The animal-based data seem to support an association between tooth loss and Alzheimer's disease better than the human evidence. Taslima et al [50] recently showed that tooth loss in wild-type mice is associated with increased levels of proteins activated by chronic stress, which activated microglial cells. Sakamoto et al [51] demonstrated that occlusal rehabilitation in rats improved spatial memory and increased neuron density.…”

“…Animal experiments have shown an association between tooth loss and cognitive impairment [46][47][48][49][50]. Que et al found that tooth loss induces memory impairment and neuronal cell loss in a mouse model [47].…”

“…These authors concluded that oral care is especially important and may reduce the risk of cognitive dysfunction. In another publication [50], Taslima and colleagues demonstrated that tooth loss in wild-type mice induced memory impairment (object recognition test) by decreasing neuronal activity and synaptic density in the hippocampus. They also demonstrated that tooth loss was associated with increased levels of protein kinase JNK and heat shock protein 90 (proteins activated by chronic stress), which activated glial cells in the hippocampus.…”

Cognitive decline in Sprague–Dawley rats induced by neuroplasticity changes after occlusal support loss

“…Previous studies have shown that loss of teeth can lead to decreased activation and degenerative changes in hippocampus 24–27 . As occlusal support loss must be accompanied by reduction and loss of masticatory activation, we assume that not only the ascending nerve pathway, but also the hippocampus will show negative plasticity changes, which may explain the memory loss.…”

The Masticatory Activity Interference in Quantitative Estimation of CA1, CA3 and Dentate Gyrus Hippocampal Astrocytes of Aged Murine Models and under Environmental Stimulation

“…Furthermore, the number of astrocytes in the hippocampus of experimental animal models has been shown to be susceptible to masticatory disorders [ 20 ]. Taslima et al (2021) [ 26 ] showed that tooth extraction in AD model mice resulted in an increase in the number of hippocampal astrocytes. Astrocytic changes linked to morphological complexity in the DG molecular layer and changes in laminar distribution in CA1 were also observed, mainly when reduced activity was associated with aging and a depleted environment [ 17 , 27 ].…”