Respiratory activity in the 6-hydroxydopamine model of Parkinson's disease in the rat.
Respiratory disturbances accompany Parkinson's disease. Weakness of the respiratory muscles or lowering of central respiratory drive might be responsible for respiratory disability. Striatal injection of 6-hydroxydopamine (6-OHDA) simulates motor symptoms of Parkinson's disease in the rat. Present study investigated whether unilateral infusion of 6-OHDA into the striatum may evoke respiratory disorders and therefore be a model for the study of the respiratory aspects of Parkinson's disease. Two weeks after the infusion the animals were anesthetized, vagotomized, paralyzed and artificially ventilated. Neural respiratory activity in the vehicle and 6-OHDA treated groups of animals was assessed from the peak amplitude of the phrenic and hypoglossal bursts, frequency of bursts and minute activity during baseline ventilation and acute intermittent hypoxia composed of five 1.5 minute long episodes of 11 percent oxygen introduced every 3 minutes. An impairment of dopaminergic pathways by 6-OHDA evoked separate effects on phrenic and hypoglossal activity. Under baseline conditions the respiratory parameters taken from the integrated phrenic nerve activity unchanged, while the preinspiratory part of the hypoglossal activity (pre-I HG) was reduced both in terms of its onset and amplitude. 6-OHDA did not affect the phrenic response to acute intermittent hypoxia but it increased the hypoglossal response (Fig. 2). Hypoxia activated the pre-I HG in both experimental groups. Although the pre-I HG increased strongly during hypoxic stimulation, the ratio of the pre-inspiratory hypoglossal amplitude to the inspiratory hypoglossal amplitude never achieved similar values as in the sham group. This ratio decreased significantly during secondary decline of the hypoxic respiratory response. A decline of the hypoxic response was more intense in the hypoglossal activity than in the phrenic activity and moved into hypoxic apnoea more frequently in the Parkinson's disease model. The results indicate a differential modulation of the phrenic and hypoglossal neural output with increased chemical drive when dopaminergic pathways were impaired by 6-OHDA suggesting that such a mechanism may contribute to respiratory insufficiency in Parkinson's disease. An involvement of a modified mechanism of dopamine efflux and of serotonin and orexin during hypoxia is suggested in the observed changes in the hypoglossal activity in the 6-OHDA model of PD.
Department of Respiratory Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland, k.budzinska93@upcpoczta.pl.
Krystyna
K
Budzinska
Kryspin
K
Andrzejewski
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D007002:Hypoglossal Nerve / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology*; D010791:Phrenic Nerve / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012120:Respiration Disorders / Q000209:etiology*
D018663:Adrenergic Agents; D016627:Oxidopamine