Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3–5 day-old flies, from 15–20 and from 27–30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments.
Highlights
Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders and is usually described by the overt clinical motor triad: tremor, bradykinesia and rigidity
It must be emphasized that the substantia nigra, whose impairment plays a key role in the motor impairment, is involved only in a later step in PD, while typical PD-related alterations can initially be observed in the anterior olfactory nucleus
PINK1B9 Mutants Display Shortened Longevity To determine the longevity of PINK1 mutant flies, individuals were examined for their life span and compared to wild type (WT) flies
Summary
Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders and is usually described by the overt clinical motor triad: tremor, bradykinesia and rigidity. Previous studies have demonstrated that several non-motor symptoms may precede the onset of motor impairment [1] [2] Of these symptoms, a decreased olfactory function in PD is a common finding, which likely occurs early in the disease process [3]. According to neuropathological studies in humans [6], it is clear that the PD-related intraneuronal pathology evolves through at least six progressive steps, which include the medulla oblongata and olfactory bulb to the midbrain, diencephalic nuclei and neocortex In this context, it must be emphasized that the substantia nigra, whose impairment plays a key role in the motor impairment, is involved only in a later step in PD, while typical PD-related alterations can initially be observed in the anterior olfactory nucleus
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