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Sense of Smell, Lost to Ills Like Parkinson’s, Appears Quite Complex

sense of smell and Parkinson's

The way that cells in the nose sense scents is more complicated than previously thought, a study reports.

A better understanding of this system could be important to interpreting better how the brain processes scents, and in understanding neurological diseases, like Parkinson’s, where loss of smell is a common early symptom.

The study, “Widespread receptor-driven modulation in peripheral olfactory coding,” was published in Science.

Our sense of smell allows us to detect chemicals in the air, which our brains interpret as various scents or odors.

“The mammalian nose is arguably the best chemical sensor on the planet, able to detect and discriminate among a large and diverse repertoire of mostly small, organic molecules,” the researchers wrote.

Deep in the nose is the olfactory epithelium, which contains thousands of nerve cells, called olfactory sensory neurons (OSNs, also called olfactory receptor neurons or ORNs). Each OSN expresses one specific type of chemical receptor. Because of this, it has long been assumed that individual ‘scent molecules’ activate particular receptors. Experiments using single scents have also supported this framework.

However, scents rarely come one-by-one in the real world. Indeed, most scents are actually combinations. “Even a simple cup of coffee has [more than] 800 volatile components,” the researchers wrote.

This example suggests that, in a scent mixture, each individual scent component activates certain receptors.

Then, the individual signals are sent to the brain, where they are combined into a single scent that is perceived — this is how other senses, like vision, work. However, this has been hard to test in olfaction, in large part because technology to monitor our many different olfactory sensory neurons simultaneously hasn’t existed.

Researchers here took advantage of a recently developed technology called SCAPE (Swept Confocally Aligned Planar Excitation) microscopy. This technique “allows the responses of thousands of single neurons within the intact olfactory epithelium to be monitored in parallel during delivery of repeated odor combinations,” they wrote.

“SCAPE microscopy has been incredibly enabling for studies where large volumes need to be observed at once and in real time,” Elizabeth Hillman, PhD, a study co-author and professor at Columbia University, said in a press release. “Because the cells and tissues can be left intact and visualized at high speeds in three dimensions, we are able to explore many new questions that could not be studied previously.”

The researchers exposed mice to three scents: one described as almond, on as floral (jasmine), and one as citrus. The responses of thousands of OSNs in their noses were measured in response to each of these scents individually, or in combinations of two or three.

Some of the OSNs behaved as expected — that is, they were activated when a given component was present, and not activated otherwise. However, many OSNs had more complicated responses.

“We expected the response to a mixture of odors to look a lot like the sum of responses to the original odors,” said Stuart Firestein, PhD, a study co-author and Columbia professor. “Instead, we observed complex interactions where a second odor enhanced a neuron’s response to the first odor, or in other cases, inhibited [prevented] a neuron’s response.”

Additional experiments using other smells had similar results.

These findings suggest that the way smells are initially perceived by our sensory systems is more complex than previously thought.

Importantly, they suggest that smell may be distinct from other sensory systems — in vision, for instance, receptors are activated by certain wavelengths of light, and the brain then combines these signals into an image.

“Olfaction thus appears unusual in using stimulus-induced complex activity starting at the level of primary sensory receptors,” the researchers wrote.

Researchers speculated that this more complicated sensory system might allow for a more nuanced sense of smell. If there were truly a one-to-one relationship between scent molecules and receptors, then mathematically, there would be a hard limit to the number of different odors that could be sensed, since humans have a limited number of receptors (about 400 total).

The more nuanced system observed, characterized by activation, inhibition, and enhancement all in combination, might have evolved to expand the olfactory system’s sensitivity to different smell combinations.

Beyond improving our understanding of brain biology, these findings may be relevant to disease.

In some disorders — including Parkinson’s, Alzheimer’s, and COVID-19 — losing the sense of smell can be an early symptom. Better understanding how this sense works could help in finding ways to better detect and diagnose these diseases.

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New Parkinson’s Treatment Target – Drp1 Protein Linked to Sense of Smell – Found in Rat Model, Study Reports

Drp1 Protein Sense of Smell

A new potential target for treating Parkinson’s, a protein named Drp1, has been identified using a rat model of the disease, a study reported.

The target was found to play a central role in the underlying cause of the degeneration and inflammation of nerve cells in the olfactory bulb, the area responsible for the sense of smell. Losing the sense of smell is an early symptom of the progressive neurodegenerative disease. 

The study, “Drp1, a potential therapeutic target for Parkinson’s disease, is involved in olfactory bulb pathological alteration in the Rotenone-induced rat model,” was published in the journal Toxicology Letters.

One early non-motor symptom of Parkinson’s is a loss of the sense of smell. Before it appears in the brain, the toxic buildup of the protein alpha-synuclein — a hallmark of the condition — occurs in the olfactory bulb, which is the the neural structure located above the sinuses that’s responsible for the ability to smell. 

However, the underlying mechanism that leads to early-stage olfactory bulb impairment is unclear.

A common phenomenon in Parkinson’s is the improper functioning of the mitochondria, or the small structures within the cell that produce energy — the cells’ powerhouses. A protein called dynamin-related protein 1 (Drp1) regulates mitochondria dynamics, notably in the cell division process. Chemicals that target this protein have been shown to cause mitochondrial fragmentation leading to the loss of neurons. 

Mitochondrial fragmentation also is known to drive a pro-inflammatory response, a common characteristic of neurodegenerative diseases. 

This prompted researchers to investigate whether Drp1-mediated mitochondrial damage played a role in the impairment of the olfactory bulb. The team used a rat model in which Parkinson-like symptoms were induced by the infusion of rotenone, a mitochondria inhibitor.

To examine the effects of rotenone on the olfactory bulb, a group of rats were treated and compared with a group of untreated rats. In a second experiment, these two groups of animals were compared with a third group treated with a specific Drp1 inhibitor.

Compared with the untreated group, rats treated with rotenone lost more weight and displayed parkinsonian features such as poor motor coordination. The treated rats also had a characteristic depletion of dopamine — the chemical messenger or neurotransmitter produced by dopaminergic neurons that are progressively lost in Parkinson’s disease.

An examination of olfactory tissue under the microscope showed that the density of dopamine-producing neurons was significantly reduced in rotenone-treated rats compared with the untreated group. 

Rotenone triggered the activation of olfactory-specific astrocytes — star-shaped neuroglia or neural support cells — and microglia, a type of brain-specific immune cell. The accumulation of these cells was accompanied by a significant increase in the production of pro-inflammatory markers. 

An examination of the mitochondria in the control animals found typical rod-like shapes characteristic of healthy olfactory cells. In contrast, large numbers of mitochondria in the rotenone-treated group were small and damaged. 

Rotenone injection also caused a dramatic reduction of Drp1 outside of the mitochondria and a significant increase on the inside. 

Finally, the researchers found that adding a Drp1 inhibitor led to a significant reduction in the loss of dopaminergic neurons, increased the presence of healthy mitochondria, and blocked the production of pro-inflammatory markers. 

“In summary, the present findings demonstrate that Drp1-mediated mitochondrial fragmentation induced by rotenone injection participated in neuropathologic changes in the olfactory bulb,” the researchers concluded. 

They said further study needs to be done “to elucidate the network as well as focus on the aberrant mitochondrial dynamics to explore the mechanism.”

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In Addition to a Cure for Parkinson’s, What Else Do We Really Want?

things

We all want something in life. We want to win the lottery or find our perfect mate. For those of us with a chronic illness, we’d be more than satisfied with a cure for our disease. 

Until we find a cure for Parkinsons’s disease, I’ve compiled a list of things that might help people with the disease to live with greater ease:

1. Some Parkinson’s patients would do anything to regain their sense of smell. It is a brighter day when we get a whiff of a rose’s fragrance or the aroma of garlic bread.

2. We want to feel good. I’m not merely referring to the absence of nausea, although that comes into play with all of the medications that can make us feel sick. We also want to feel positive about ourselves despite this disease taking so much from us.

3. We often feel that we have nothing left to offer, and we would like someone to remind us that we still have a purpose despite Parkinson’s.

4. I’ve heard of people with Parkinson’s whose family members or friends believed they were pretending to have the disease. Here’s what I say to them: “Don’t you think we have better things to do with our time than pretend to have an incurable disease?”

5. We want others to understand that although some of our symptoms can be hard to see, the disease is real. Our tremors, pain, lack of balance, and risk of falls are genuine.

6. Parkinson’s disease can be summed up as a loss of dopamine in the brain.

7. Our constant companion is this little monster, but we would like a reprieve from frequent shaking.

8. It would be fantastic if others were aware of the struggles and invisible symptoms that we live with so that they can fully understand the urgency of a cure.

9. It is common for people with Parkinson’s to experience sleepiness as a symptom and as a medication side effect. As a result, we can spend a good deal of our day sleeping. We also struggle to get a good night’s sleep. It can be a vicious cycle. We would love a treatment that doesn’t knock us out for half of the day but instead knocks out Parkinson’s.

10. Besides having a little plastic bat to bonk others over the head when they make thoughtless comments such as, “You don’t look like you have Parkinson’s disease,” a cure would also be welcome!

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Scientist Lands $5M Grant to Study Link Between Pesticides, Smell and Parkinson’s

pesticides and Parkinson's

The National Institutes of Health (NIH) has granted a Michigan State University scientist $5 million to study a possible link between pesticides, a diminished sense of smell, and early symptoms of diseases such as Parkinson’s among older farmers.

The investigator is Honglei Chen, MD, PhD, a professor of epidemiology whose research focuses on neurodegenerative disorders. His primary scientific interests include environmental and genetic risk factors for Parkinson’s disease.

“Our battle against Alzheimer’s and Parkinson’s may depend on early disease identification and intervention, and poor olfaction [sense of smell] has been identified as an early warning for these diseases,” he said in a press release.

“This grant will allow us to connect the dots by identifying factors that contribute to poor olfaction among older adults, and evaluating how this sensory deficit may progress to early stages of neurodegenerative diseases,” Chen said.

Early analyses, published in the journal Environmental Health Perspectives, revealed a link between high pesticide exposure and a self-reported impaired sense of smell.

The team studied more than 11,200 farmers, of whom 16% experienced a high pesticide exposure event, over a 20-year period. At the end of the study, participants were asked if they suffered a partial-to-complete loss of sense of smell. Those who were exposed to high pesticide levels were 50% more likely to report a poor sense of smell. Importantly, an immediate washing with soap and water after a large amount of pesticide contacting the body, for example, could lower this risk.

A study published last December in the Journal of Neurology suggested that an impaired sense of smell or taste can raise an individual’s risk of developing Parkinson’s disease 2.5 times. Presently, Parkinson’s is diagnosed chiefly through assessment of motor symptoms and their severity. However, non-motor symptoms have gained attention due to their potential to predict Parkinson’s-related motor symptoms.

Chen and his team will use the grant to measure the ability to smell among roughly 2,200 farmers. After using a scratch-and-sniff method to try to identify a dozen common smells — smoke, lemon and cinnamon, for example — some 450 farmers will get a home visit from researchers who will test the farmers’ cognitive function and motor symptoms.

Researchers are using resources from the Agricultural Health Study (AHS) and its NIH scientists, along with research assistance from partners at Duke University, the University of Chicago and Penn State University.

A collaboration of the National Institute of Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), the Environmental Protection Agency (EPA) and the National Institute for Occupational Safety and Health (NIOSH), the AHS is a prospective investigation of licensed pesticide applicators from North Carolina and Iowa who were recruited for the study from 1993 to 1997.

Through 2014, after rounds of questionnaires, a telephone interview, and collecting a buccal-cell DNA sample, follow-up is ongoing to see what, if any, diseases develop among study subjects.

In addition, researchers annually link the study group to state cancer registries and vital records to monitor cancer incidence and mortality.

The AHS is believed to be the world’s largest study of farmers and their families.

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