Smells Like Parkinsonís Disease
Posted by Dr. Pulkit Agarwal on
Friday, 25th May 2012
Parkinsonís disease has always been primarily seen as a movement disorder resulting in symptoms of shaking, tremors, rigidity, and trouble walking. Interestingly, however, at least 90% of patients with Parkinsonís experience either loss or decreases in the sense of smell. Studies have shown that problems with olfaction actually generally precede the onset of other motor symptoms. Most people are not personally aware of changes in their olfactory acuity, but the increasing range and prevalence of smell tests offer a quick, easy, cheap, and non-invasive diagnostic test, as well as a measure of disease progression. In addition, the shift of focus for researchers from Parkinsonís as a motor disorder to a more global neurodegenerative disorder allows consideration of new paradigms about the causes and disease progression.
The cellular basis of olfactory dysfunction in Parkinsonís remains an enigma. Post-mortem studies have confirmed shrinkage of the olfactory bulb, but this fails to shed light onto the root causes as it only demonstrates the end effect. Experimental models of Parkinsonís have demonstrated various results such as protein aggregation in the olfactory bulb, changes in levels of neurotransmitters, microglial activation, and loss of cells in the olfactory bulb. However, as all of these effects are inter-related, none of these clarify the actual initial cause of damage.
Many of the hypotheses as to why olfactory dysfunction occurs and precedes other symptoms remain grounded in the long-held paradigm of Parkinsonís as a motor disease caused by the loss of dopaminergic neurons in the substantia nigra. For example, in some experimental models an increase in dopamine was found in the olfactory bulb. The researchers suggested this occurs as a compensatory mechanism in response to the loss of dopamine in the substantia nigra. As it has also been shown that sense of smell is particularly vulnerable to changes in dopamine, excess dopamine in the olfactory bulb would, thus, lead to olfactory dysfunction.
However, a number of other theories have been proposed suggesting that perhaps the olfactory bulb is the first brain structure to exhibit signs of damage because Parkinsonís could be caused by respiratory viruses or inhaled toxins that enter the brain through the nose. The cause of Parkinsonís has not been conclusively determined. And while a genetic component has been uncovered, the causes are clearly much more complex with various environmental factors involved. A number of studies have been performed demonstrating Parkinsonís-like symptoms following exposure to viruses, heavy metals, and pesticides in experimental models. Epidemiological studies have also linked pesticides exposure to an increased risk of Parkinsonís. It is certainly an interesting hypothesis that inhaled toxins could cross the blood brain barrier, and that the damage in Parkinsonís could begin first in the olfactory bulb and then spread from there to the substantia nigra. In addition, as the olfactory bulb is heavily involved in adult neurogenesis, any damage to this structure could severely limit the brainís ability to repair itself by replenishing damaged neurons with new ones. Perhaps, then, Parkinsonís disease does not depend on a single source of damage, but rather multiple insults occurring. For example, genetically induced damage to the dopaminergic neurons in the substantia nigra combined with inhaled toxins damaging the olfactory bulb could, together, cause Parkinsonís, while one or the other would be insufficient.