Parkinson’s
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 Parkinson’s 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 Parkinson’s 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 Parkinson’s
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 Parkinson’s 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 Parkinson’s 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.
Epidemiological studies have also linked pesticides exposure to an increased risk of Parkinson’s. It is certainly an interesting hypothesis that inhaled toxins could cross the blood brain barrier, and that the damage in Parkinson’s 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 brain’s ability to repair itself by replenishing damaged neurons with new ones. Perhaps, then, Parkinson’s 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 Parkinson’s, while one or the other would be insufficient.
References
Prediger, R., Aguiar, A., Matheus, F., Walz, R., Antoury, L., Raisman-Vozari, R., & Doty, R. (2011). Intranasal Administration of Neurotoxicants in Animals: Support for the Olfactory Vector Hypothesis of Parkinson’s Disease Neurotoxicity Research, 21 (1), 90-116 DOI:10.1007/s12640-011-9281-8
Doty, R. (2011). Olfaction in Parkinson’s disease and related disorders Neurobiology of Disease DOI: 10.1016/j.nbd.2011.10.026
Ubeda-Bañon, I., Saiz-Sanchez, D., Rosa-Prieto, C., & Martinez-Marcos, A. (2011). ?-Synuclein in the olfactory system of a mouse model of Parkinson’s disease: correlation with olfactory projections Brain Structure and Function DOI: 10.1007/s00429-011-0347-4
