Sensory regions of brain disrupted in Parkinson’s: Mouse study
Scans might detect disease in people with sight, smell deficits
Nerve cells in the brain that are responsible for processing smells and sight show deficits in Parkinson’s disease, according to research done in a mouse model.
The findings may lay the groundwork for new approaches to diagnose Parkinson’s, according to scientists.
“I think this work is a nice first demonstration of the fact that we can detect multisensory impairments in the brain fairly robustly,” Noam Shemesh, PhD, co-author of the study and leader of the preclinical MRI lab at the Champalimaud Foundation in Portugal, said in a foundation news story. “And it gives us some hope that, with future studies, there will be more things we can look at that hint at early development stages of PD [Parkinson’s disease] and also determine which treatments might help if they’re given early on.”
The study, “Neural and vascular contributions to sensory impairments in a human alpha-synuclein transgenic mouse model of Parkinson’s disease,” was published in the Journal of Cerebral Blood Flow & Metabolism.
Parkinson’s disease is characterized by motor symptoms, but it also commonly causes issues with the senses. Loss of the sense of smell is frequently an early nonmotor symptom of Parkinson’s. People with Parkinson’s also may experience problems with vision ranging from reduced visual acuity to hallucinations.
Tracking pathways in brain’s sensory regions
Although it’s well established that these sensory issues are common in Parkinson’s, there hasn’t been much research into how the disease affects pathways in the brain that are responsible for controlling vision and smell. To learn more, scientists conducted a series of experiments using a mouse model engineered to make a human version of alpha-synuclein, a protein that characteristically forms toxic clumps in the brains of people with Parkinson’s.
To track brain activity, the researchers used an imaging technology called functional magnetic resonance imaging (fMRI). In essence, fMRI works by identifying which parts of the brain have more blood flow and electrical signaling, indicative of increased activity.
“The vast majority of fMRI studies in animal models focus on a single sense,” Shemesh said. “We analysed both visual and olfactory [smell] sensory modalities. That’s pretty rare in fMRI experiments.”
The researchers found that when they exposed alpha-synuclein-expressing mice to flashing lights or odors, the parts of the mice’s brains responsible for processing vision and smell were significantly less active than in healthy mice that don’t express alpha-synuclein.
This reduction in activity could potentially be driven by decreased activity of neurons (nerve cells), but it also could reflect reduced blood flow to these parts of the brain — a limitation of fMRI is that it cannot easily distinguish between the two. To gain more clarity, the researchers measured levels of C-FOS, a protein released when nerves are active, in the mice’s brains. This indicated that, although blood flow was slightly decreased, most of the decrease in activity was due to the neurons themselves.
“To our knowledge, this is the first observation of a combined visual and olfactory sensory aberration in the brain activity of PD rodent models in general and the alpha-synuclein model in particular,” the researchers wrote.
The findings may have implications for how Parkinson’s is diagnosed, the researchers said. A diagnosis of Parkinson’s is made based on the appearance of motor symptoms, but the study data imply it may be possible to detect early signs of the disease by looking for dysfunction in parts of the brain responsible for processing sensory information.
“Assuming that the effects of alpha-synuclein in the mouse brain and in the human brain are similar, which I think is a reasonable assumption, one of the things we could now do would be to check fMRI signals in the brain of people who are reporting some [loss of smell], as well as their visual responses,” Shemesh said. “And if we saw something weird in both sensory modalities, we could potentially say that there is something more global happening in their neural circuits, and that we need to follow up on that.”
Tiago Outeiro, PhD, study co-author and a neuroscientist at the University Medical Center Gottingen in Germany, said this type of diagnostic approach would be “truly non-invasive and easy to perform” and “could add to the toolbox for diagnosing and classifying [Parkinson’s], something that is urgently needed.”
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