No, this is not a blog entry about sinusitis, rhinitis or epistaxis (how doctors refer to a bloody nose). It involves an evolutionary discussion of nasal function, anatomy, and connections with prevalent modern day health problems.
In human physiology, the chemical senses (smell and taste) play minor roles compared to vision, hearing and touch. However, it is well-known that a number of odors can involuntarily elicit access to memories, thought to be forgotten. Likewise, intense memories can sometimes produce specific olfactory (smell related) experiences. Olfaction also has a significant impact on human social behavior and mood.
The olfactory system provides for the detection of volatile chemical substances. The receptor cells are located in the mucosal surface of the nose. They reside high in the nasal cavity where it comes into intimate contact with the base of the brain cavity (located behind the bridge of the nose). This is where receptor neurons (called bipolar olfactory receptor neurons) reside. They are able to detect the roughly 5,000 odors humans are able to differentiate. Once stimulated, these neurons transmit an impulse to a relay station (the olfactory bulb) located within the brain cavity. From here the impulse is transmitted directly to the cerebral cortex - that thin layer of nerves that comprises the gray matter overlying the brain. It forms a series of hills and valleys and is what you first observe when you look at the surface of the brain. The primary destinations of the nerve cells that originate in the olfactory bulb are the entorhinal cortex and the amygdala. The entorhinal cortex is where much of the processing occurs that creates mental awareness of a specific odor. The amygdala is part of the limbic system, an ancient anatomic region that contributes to memory function and visceral responses including fear, anxiety and stress. It is no accident these are described as being visceral, because, as you can see from their anatomic connection with the nose (a key participant in detecting and processing the aroma of freshly cooked food) they are linked with the digestive tract. The intimate relationship of the 'nose brain' with memory, learning, and emotional traits is also intriguing.
Specific odorants (volatile chemicals that contact the olfactory receptor neurons which generate an electrical signal that is transmitted to the brain) are stimuli our nose detects and our brain uses to create a mental image it associates with that chemical. This mental picture the brain creates is what is referred to as an odor. Think of a bottle of chemicals used to clean paint brushes. That is the odorant. When we smell it, the mental image of 'turpentine' is generated. This is the odor, or smell we perceive. Using a visual analogy, the wooden platform with four legs used for writing is perceived as a desk. Since odors are mental constructs, they may be subject to additional mental processing and may even be perceived differently dependent on subsequent personal experiences.
Chemical senses, including smell, play an important role in the animal kingdom. They have been used as a method of communication with other members of the species, for detection of food, for identification of potential environmental dangers such as larger animals on the prowl or rancid potentially toxic food, and for reception of biological signals pertinent to mating and reproductive processes. Olfactory signals differ from typical visual or auditory stimuli in that they are frequently transient, but are often extraordinarily complex. For example, the aroma of coffee is made up of more than 800 volatile components. It is also difficult to 'label' smells and as a result they are often described by the situation in which they are encountered such as "this smells like Christmas."
Olfactory signals also provide discriminatory functions in social interactions by allowing for the identification of individuals. For example, mothers are able to identify their newborn babies by odor after only a brief exposure (less than an hour).
These examples serve to underscore the intimate connectivity between odors, nasal function, and the brain. The anatomical infrastructure is primitive and the link to survival benefits for the organism suggests a long-standing important nexus between the olfactory system and and vital aspects of human physiology.
If we fast forward to modern times, the current epidemics we are confronted with include obesity (and the closely associated disorders diabetes and cardiovascular disease) and various states of mental decline including Alzheimer's disease (AD). These conditions don't exist in isolation. Obesity increases the risk of developing AD two or three-fold. There have also been links established between impaired olfactory function and AD. This is not surprising given the close proximity, intimate connectively, and anatomic overlap between the nose brain and the vital memory center called the hippocampus. In fact, the earliest neuropathological findings identified in the brains of patients with AD occur in the nose brain (entorhinal cortex). From here, they spread throughout the brain. Convergent data reveal that AD patients show impaired olfactory performance, specifically in tasks of odor identification. Recently, an association was found between decreased olfaction and diminished left hippocampal volume in persons with probable AD. Loss of the sense of smell (not related to sinus and other local diseases) has been identified as a predictor for later cognitive decline in non-demented elderly retirees. There are starting to be early hints that obesity might also be associated with altered olfactory function. A study documented modified olfaction in obese children aged 10 to 16 years. Clearly, more studies are required to investigate this correlation. Hence, there are links between impairments of olfactory function and both AD and the obese state.
Thus it appears there is a link between obesity, AD and the nose brain. The question might be asked, what is its substrate. Clues to this exist. Numerous investigators have identified decreased insulin signaling in the brains of patients with AD. This has been documented in animal models of AD. In addition, when insulin levels in the brain are evaluated, they are lower in AD than in age equivalent normals. AD patients are frequently found to be insulin resistant. This means their bodies don't react normally to the hormonal effects of insulin. Insulin is the hormone that regulates and controls blood sugar levels. With a diminished response to insulin, blood sugar levels rise and higher insulin levels are needed to bring them back to normal. As insulin levels rise in the bloodstream, they fall in the brain. One reason for this is that insulin in the blood can't be as effectively transported to the brain because of modifications in the blood-brain-barrier (BBB). Animals with lowered brain insulin develop mental decline and memory loss. In short, they become demented.
The same findings exist in obese, non demented persons. That is, they have lower brain insulin levels. One effect of brain insulin is that it decreases appetite. This makes the connection seem potentially causal. It would be interesting to find out whether deviations in olfaction constitute a common feature of states of insulin deficiency in the brain associated with obesity and AD. This is not far fetched because there are high levels of insulin receptors in the nose brain.
Whether this is true, or not, the nose-brain connection may provide a therapeutic route for treatment. Over the years spontaneous passage from the nose to the brain has been documented for viruses, heavy metals and bioactive peptides such as CCK (cholecystokinin). More recently, investigators have documented the passage of nasally applied insulin (the same hormone used to regulate blood sugar) across the nasal mucosa into the brain. In addition, they have shown enhanced focus, memory, and performance of daily activities in patients with early AD who had been studied after intra-nasal application of insulin.
These astounding observations should serve as an incentive to pursue additional research in the nose-brain connection including its potential as a therapeutic conduit for some of the common health concerns afflicting many persons today.