Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy

Tsuda, Takuya; Oda, Hiroshi; Okabe, Shinichi; Kikuchi, Yoshihiro; Itoyama, Yasuto

doi:10.1002/ana.10296

Cited by 58 publications

(35 citation statements)

References 14 publications

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“…Thus, A5 neurons appear to participate in complex cardiorespiratory interactions, including those associated with sympathetic responses to hypoxia. Therefore, it is conceivable that involvement of these neurons may contribute to respiratory [8,26] or cardiovascular [25] manifestations of MSA. However, given that the role of A5 neurons is not fully characterized by experimental studies, our conclusions regarding their potential contribution to cardiorespiratory manifestations of MSA are speculative at this point.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple system atrophy (MSA) may manifest with prominent impairment of sympathetic cardiovascular and respiratory control [8,26]. Whereas MSA is associated with loss of noradrenergic neurons in both the locus ceruleus [1,13] and A1 area of the caudal ventrolateral medulla [2], involvement of neurons of the A5 group has not been systematically explored.…”

Section: Introductionmentioning

confidence: 99%

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Loss of A5 noradrenergic neurons in multiple system atrophy

et al. 2008

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The A5 noradrenergic group of the pons projects on the medulla and spinal cord and contributes to control of sympathetic activity and respiration. Because these functions are affected in multiple system atrophy (MSA), we sought to determine whether there was involvement of A5 neurons in this disorder. We counted tyrosine-hydroxylase (TH) immunoreactive neurons in the A5 area and locus ceruleus in the pons obtained from six patients with clinical and neuropathological diagnoses of MSA and six age-matched controls using stereological methods. There was a severe loss of A5 neurons in MSA (total cell number 3,215 ± 258 in controls and 321 ± 62 in MSA, P < 0.001). The severity of cell loss was comparable to that of locus ceruleus neurons in these cases. Our results indicate that A5 neurons are severely affected in MSA and this may contribute to some of the manifestations of this synucleinopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of A5 noradrenergic neurons in multiple system atrophy

et al. 2008

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“…Sleep-related breathing problems in MSA mainly consist of (1) upper airway obstruction, such as vocal cord abductor paralysis (VCAP) [6], (2) abnormal respiration due to impairment of the respiratory center [3,7,8], and (3) impaired hypoxemic ventilatory response [9]. VCAP, which results in obstructive sleep apnea, is attributed to a loss of vagal motoneurons in the nucleus ambiguous (NA) [10,11] or dystonia of the vocal cords due to supranuclear impairment [12,13].…”

Section: Introductionmentioning

confidence: 99%

The close relationship between life-threatening breathing disorders and urine storage dysfunction in multiple system atrophy

et al. 2010

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Survival of multiple system atrophy (MSA) depends on whether a variety of sleep-related breathing problems as well as autonomic failure (AF) occur. Since the brainstem lesions that cause respiratory and autonomic dysfunction overlap with each other, these critical manifestations might get worse in parallel. If so, the detection of AF, which is comparatively easy, might be predictive of a latent life-threatening breathing disorder. In 15 patients with MSA, we performed autonomic function tests composed of postural challenges and administered a questionnaire on bladder condition, as well as polysomnography and laryngoscopy during wakefulness and under anesthesia. Polysomnographic variables such as the apnea-hypopnea index (AHI) and oxygen saturation (SpO(2)) and the findings of laryngoscopy were compared with the degree of cardiac and urinary autonomic dysfunction. AHI, mean SpO(2) and the lowest SpO(2) showed significant correlations with urine storage dysfunction. In addition, patients with vocal cord abductor paralysis (VCAP) or central sleep apnea (CSA) contributing to nocturnal sudden death had more severe storage disorders than those without. On the other hand, no significant relationship between polysomnographic variables and orthostatic hypotension was observed except in the case of mean SpO(2). These results indicate that life-threatening breathing disorders have a close relationship with AF, and especially urine storage dysfunction. Therefore, longitudinal assessment of deterioration of the storage function might be useful for predicting the latent progress of VCAP and CSA.

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“…After unilateral preBö tC ablation, there was no significant difference in the responses to hypercapnia or hypoxia during wakefulness; however, impaired chemosensitivity is a symptom of bilateral preBö tC ablation (4) and may reflect a role for the preBö tC in integrating chemoresponsive information. Notably, patients with MSA or PD also have impaired chemosensitivity to hypoxia (49,50), and in patients with MSA there is a depletion of glutamatergic and serotonergic neurons, putative chemoresponsive neurons, within the ventral medullary surface (51).…”

Section: Discussionmentioning

confidence: 99%

Unilateral Ablation of Pre-Bötzinger Complex Disrupts Breathing during Sleep but Not Wakefulness

McKay

Feldman

2008

Am J Respir Crit Care Med

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Rationale: In adult rats, bilateral ablation of pre-Bötzinger complex (preBötC) neurokinin 1-expressing (NK1R) neurons leads to a progressive and irreversible disruption in breathing pattern, initially during sleep, eventually resulting in an ataxic breathing pattern during wakefulness. Objectives: Here we determine whether ablation of fewer preBötC NK1R neurons leads to a persistent pattern of disordered breathing during sleep but not during wakefulness. Methods: Adult male Sprague-Dawley rats (n 5 12) were instrumented to record diaphragmatic, abdominal, and neck EMG, and EEG. Fourteen days later, a second surgery was performed to stereotaxically microinject into the preBötC on one side the toxin saporin conjugated to substance P (SP-SAP), which selectively ablates NK1R neurons. Measurements and Main Results: Postinjection, rats were monitored within a plethysmograph until they were killed (Days 21-51). At Days 6-9 post-unilateral SP-SAP injection, respiratory pattern during sleep, particularly REM sleep, became increasingly disordered, characterized by an increase in frequency of central sleep apnea and hypopneas (36.8 6 7.4 episodes/h of REM vs. 6 6 2.0 episodes/h in preinjection controls; P , 0.05), whereas breathing during resting wakefulness remained stable. Unlike bilateral SP-SAP-injected rats, an ataxic breathing pattern did not develop during wakefulness. Rats that were monitored up to 51 days post-SP-SAP injection continued to have sleep-disordered breathing; breathing during wakefulness remained relatively stable. Histologic analysis of the ventrolateral medulla confirmed that NK1R neurons within the preBötC on the injected but not on the contralateral side of the medulla were ablated. Conclusions: Gradual loss of preBötC NK1R neurons may be an underlying factor of sleep-disordered breathing, in particular of central sleep apnea.

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Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy

Cited by 58 publications

References 14 publications

Loss of A5 noradrenergic neurons in multiple system atrophy

Loss of A5 noradrenergic neurons in multiple system atrophy

The close relationship between life-threatening breathing disorders and urine storage dysfunction in multiple system atrophy

Unilateral Ablation of Pre-Bötzinger Complex Disrupts Breathing during Sleep but Not Wakefulness

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