Deficiency of Biogenic Amines Modulates the Activity of Hypoglossal Nerve in the Reserpine Model of Parkinson's Disease.

Monika Jampolska,Katarzyna Kaczyńska,Kryspin Andrzejewski,Ilona Joniec-Maciejak,Małgorzata Zaremba

doi:10.3390/cells10030531

Abstract

The underlying cause of respiratory impairments appearing in Parkinson’s disease (PD) is still far from being elucidated. To better understand the pathogenesis of respiratory disorders appearing in PD, we studied hypoglossal (HG) and phrenic (PHR) motoneuron dysfunction in a rat model evoked with reserpine administration. After reserpine, a decrease in the baseline amplitude and minute HG activity was noted, and no depressive phase of the hypoxic ventilatory response was observed. The pre-inspiratory time of HG activity along with the ratio of pre-inspiratory time to total respiratory cycle time and the ratio of pre-inspiratory to inspiratory amplitude were significantly reduced during normoxia, hypoxia, and recovery compared to sham rats. We suggest that the massive depletion of not only dopamine, but above all noradrenaline and serotonin in the brainstem observed in our study, has an impact on the pre-inspiratory activity of the HG. The shortening of the pre-inspiratory activity of the HG in the reserpine model may indicate a serious problem with maintaining the correct diameter of the upper airways in the preparation phase for inspiratory effort and explain the development of obstructive sleep apnea in some PD patients. Therapies involving the supplementation of amine depletion other than dopamine should be considered.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after Alzheimer’s disease, associated with substantial damage of dopaminergic neurons in the nigrostriatal pathway that is responsible for the characteristic motor symptoms of the disease [1,2,3]
During a ventilatory response to acute 8% (O2 in N2 ) hypoxia (HVR), the HG nerve amplitude in the reserpine group increased three times compared to its baseline value, while in sham rats only twice (Figure 2B)
We found that a substantial disruption of the bioavailability of three biogenic amines (DA, NA, and 5-HT) that modulate respiration significantly affects the activity of vital respiratory motoneurons in a non-invasive, repetitive model of PD, widely used as a predictive indicator of likely symptomatic efficacy of new agents [31]

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after Alzheimer’s disease, associated with substantial damage of dopaminergic neurons in the nigrostriatal pathway that is responsible for the characteristic motor symptoms of the disease [1,2,3]. It is suspected that respiratory disturbances may be associated with deficits in two other monoamine systems, such as noradrenergic and serotoninergic systems, that apart from dopaminergic, are depleted in PD brains [7,8,9,10,11]. All these monoamines are transmitters of neurons present in structures important for the generation and modulation of the respiratory rhythm or neurons localized in their immediate vicinity [10,12,13,14,15,16,17,18]. OSA prevalence in PD subjects has been demonstrated in several studies [24,25,26]

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