The Link Between the Oral Cavity and Neurodegeneration

As a student on the pre-dental track, I’m often asked why I’m a neuroscience major. To many people, the oral cavity appears isolated from the rest of the body: the connection between oral hygiene and the brain is not as intuitive. Even as a pre-dental student, I’m constantly surprised at the relationships between the oral cavity and the rest of the body. We can see one incredible example of this by exploring the link between neurodegeneration and the oral cavity.

Neurodegenerative diseases result from damage or death of nerve cells, or neurons ("What is Neurodegenerative Disease?", n.d.). Since neurons of the central nervous system cannot repair or replicate to counteract this damage, this results in an extremely debilitating, progressive disease, such as Alzheimer's Disease, Parkinsons, or Multiple Sclerosis. While age is one of the biggest risk factors for neurodegeneration, an increasing amount of research highlights the importance of oral hygiene as a preventative measure. To understand why, it’s key to examine how bacteria can travel from our mouth to our brain.

Figure 1: Pathways of bacterial transmission from the oral cavity to the brain (Mishra et al., 2018)

Consider Figure 1., which shows three main ways bacteria can be transmitted to the brain. Bacteria can enter the brain directly through the olfactory tract and then the olfactory nerve into the brain. Or, bacteria within the mouth can infect the blood and be transmitted to the brain via the blood-brain barrier, perivascular space, or circumventricular organs (Mishra et al., 2018).

Evidently, oral microbiota can enter the brain through a number of pathways, but how does this actually impact neurodegeneration? To illustrate this, we can look at the consequences of microbiota on Alzheimer’s Disease (AD). AD is a devastating form of dementia in which plaques of beta-amyloid protein build up in the brain, disrupting cognitive function and especially memory (Sureda et al., 2019).

Figure 2: Mechanisms of neuroinflammation and glial activation contributing to Alzheimer's Disease by oral bacteria (Sureda et al., 2019)

As Figure 2. shows in part A, when bacteria enters the blood-brain barrier, it results in glial activation and neuroinflammation that contributes to AD. Part C shows that the entrance of bacteria also triggers a feedback mechanism that induces greater production of amyloid-B plaques and contributes to AD. Specifically, oral microbiota such as “P. gingivalis, T. forsythia and T. denticola are considered the main responsible pathogens in periodontitis, and several inflammatory responses, and have been associated with the development of AD.” It comes as no surprise that “periodontitis is associated with an increase in cognitive decline in AD,” (Sureda et al., 2019). This is just one example of how oral health can play a surprisingly critical role in our overall health, but certainly is not the only connection between our brain and oral cavity.

Beyond pathological manifestations, sometimes symptoms of neurodegenerative diseases can be exhibited within the oral cavity. Multiple sclerosis (MS) is an autoimmune disease in which neurons lose myelin, reducing the speed at which action potentials can fire and the probability that they propagate all the way down the axon terminal. Although there are periods of remission for those with MS, neurological deficits progressively become permanent and result in a loss of overall function. Some research indicates that there could be a relationship between MS and trigeminal neuralgia, an orofacial condition in which one experiences sharp periods of pain on one side of their face. One study found that “in 15% of the MS population, TN precedes the diagnosis of MS,” (Fallata et al., 2017). Evidently, the implications of this conclusion are huge: early intervention and diagnosis of MS could greatly impact quality of life and treatment options. If a patient experiencing trigeminal neuralgia is asked about other aspects of their health during their visit to an oral healthcare provider, the provider can refer them to a neurologist if they have suspicions to be on the safe side. Even if this was only caught in a handful of patients, early intervention and diagnosis would drastically benefit their quality of life.

Beyond the oral cavity’s role in diagnosis or pathology of neurodegeneration, it could also be used potentially for treatment. One promising field into treatment of neurodegeneration is actually through the use of oral-cavity derived stem cells. Stem cells are cells that have the ability to differentiate into various types of cells with specialized functions (Mayo Foundation for Medical Education and Research, 2022). Consequently, stem cells have immense therapeutic potential to treat diseases caused by cell damage or death. In particular, many researchers are looking into dental pulp stem cells as these cells are highly effective in regeneration in vitro (Ueda et al., 2020). Past studies have shown that these dental pulp stem cells (DPSC) can differentiate into both neurons and glial cells (Uzunoglu-Ozyurek et al., 2021), which means that they could treat a vast array of neurodegenerative diseases in which either type of cell is affected.

For instance, one study found that “in in vitro AD models, DPSCs release NGF, GDNF, BDNF, and other neurotrophic factors, reducing amyloid β-induced toxicity.” (Ueda et al., 202). For Parkinson’s, another study found that “in vitro, neurotrophic factors such as NGF and GDNF released by DPSCs protect midbrain neurons damaged by 6-hydroxydopamine (6-OHDA), a selective dopaminergic toxin.” A separate literature review concluded that “In vitro studies showed that the use of OCDSCs increased the viability of neuronal cells exposed to chemical agents that induced NDs and in vivo studies reported that OCDSCs improved the motor and cognitive functions of PD and/or AD animal models.” (Uzunoglu-Ozyurek et al., 2021). Moreover, DSCs are easy to obtain as they can be collected from wisdom teeth once removed, making it less invasive of a procedure overall.

Ultimately, one of the reasons why I began exploring the link between neurodegeneration and the oral cavity was to better patient care. Patients with neurodegenerative diseases require specialized attention and care to ensure that their oral health is not deteriorating. Neurodegeneration makes it harder for patients to take care of their oral health: for instance, Parkinsons (PD) patients are unable to chew and swallow effectively due to weakened motor control. Consequently, “dental disease and decay should be prevented and treated in order to diminish and compensate for the impairment in the control of masticatory and tongue muscles.” (Zlotnik et al., 2015). Additionally, oral healthcare providers should be aware of the effects of the disease on their patients and make specific adjustments. Decreased swallowing ability of PD patients puts them at greater risk for asphyxiation and their tremors can make it difficult to keep their tongue still during dental work , which I saw firsthand while shadowing (Dental Health in Parkinson’s, n.d.). Recognizing these barriers can help a provider craft a specialized treatment plan to ensure that the patient is as comfortable as possible while still delivering the highest quality of care. As a future healthcare professional, I believe it’s important to recognize that treating patients requires an interdisciplinary approach and exploring the link between neurodegeneration and the oral cavity is just one way I can begin to do this.

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