Karl, I don't know if there's a connection to your use of that machine or not. But other studies say the same thing:

"Parallel results indicating that reduced oxygen levels can also promote the survival, proliferation, and catecholaminergic differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels."

From:

Culture in Reduced Levels of Oxygen Promotes Clonogenic Sympathoadrenal Differentiation by Isolated Neural Crest Stem Cells

http://www.jneurosci.org/cgi/content...act/20/19/7370

http://www.jneurosci.org/cgi/content...act/20/19/7377

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"These results suggest that although hypoxia induces an increase in the extracellular dopamine levels (hence, an apparent increase in the activity of the dopaminergic neurons), this increase is not the result of an increase in dopamine release itself, but rather the result of inhibition of the dopamine reuptake mechanism."
http://www.blackwell-synergy.com/doi...1991.tb08249.x

Well, this sort of sounds like the often referenced rock and hard place. I need the machine to breathe but it may be facilitating the progression of PD.

It sounds from the discussion that the onset of PD symptoms and the onset of sleep apnea are probably unrelated. That was my original question. I certainly wasn't expecting to learn about a possible beneficial role of hypoxemia. I had anticipated that it would make PD worse.

I'm not sure where to go from this point. At 6'3" and 210 lbs, I'm not what most would call over-weight. I am trying to get my weight down to about 190, which is what it was when I was in my 30's. It's also what I weighed when the apnea started, however. Also, Heidi has recommended a gluten-free diet. I'm looking into that as well.

Perhaps, with the right changes, I may be able to get off the CPAP machine. It has helped so much that it's difficult to accept that there may be a down side to its use.

I have to say that I'm a bit taken aback by this turn of events. Perhaps I should visit the sleep apnea forum to see what I can learn there.

Karl

Karl, I wouldn't worry about the machine making your PD worse. Possibly, the dopamine reuptake mechanism is temporarily affected, but this doesn't mean your PD is getting worse because of it. Also:

"Effects of the Obstructive Sleep Apnea Syndrome (OSAS): Patients with obstructive sleep apnea syndrome (OSAS) ( which includes difficulty sleeping, sleep fragmentation and nocturnal hypoxemia) have sown short-term memory and cognitive impairment."

That sounds pretty bad, too, so OSAS should be addressed.

Also, PWPD respond subnormally to hypoxia which can be dangerous, so it should be avoided:

Parkinson's disease and impaired chemosensitivity to hypoxia

Correspondence

Parkinson's disease and impaired chemosensitivity to hypoxia

Hiroshi Onoderaa, Corresponding Author Contact Information, Shinichi Okabeb, Yoshihiro Kikuchib, Takehide Tsudab and Yasuto Itoyamab
aDepartment of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan
bFirst Department of Internal Medicine, Sendai, Japan

Available online 1 April 2005.

Refers to: Parkinson's disease and impaired chemosensitivity to hypoxia
The Lancet, Volume 356, Issue 9247, 16 December 2000, Page 2099
Georg Röggla, Wim Weber and Martin Röggla



Authors' reply

Sir—We reported that patients with Parkinson's disease had an impaired hypoxic ventilatory response (HVR) accompanied by blunted perception of dyspnoea, even at an early stage of disease. Since dopamine decreases HVR and dopamine receptor antagonists increase HVR,1 Georg Röggla and colleagues raise an important issue; whether the disease itself or the therapy is causal for impaired HVR. We believe that Parkinson's disease itself impairs the chemosensitivity to hypoxia, as evidenced by the fact that parkinsonian patients taking no drugs that affect dopaminergic functions (levodopa, dopamine-receptor agonists, or both) had a significant reduction of HVR compared with controls.

We compared HVR in patients who had no history of taking dopaminergic drugs (mean age 54·2 years [SD 9·7]) with that in patients taking levodopa, dopamine-receptor agonists, or both (mean age 60·2 years [SD 7·6]). Patients with Parkinson's disease (Hoehn and Yahr stage 2–3) and controls (mean age 53·8 years [9·5]) did not smoke and had no history of respiratory disorders during the previous 6 months. In the hypoxic test, end-tidal carbon dioxide tension (PETCO2) was maintained at the value of each participant's resting PETCO2 during the procedure. The chemosensitivities to hypoxia were expressed as the slope of the regression line relating ventilation to changes in oxygen saturation in arterial blood calculated by least-squares linear regression analysis and measured in L/min, divided by the percentage change in saturation. All patients and controls had normal basic pulmonary functions, such as vital capacity, forced expiratory volume in 1 s, arterial oxygen tension, and arterial carbon dioxide tension.

Chemosensitivity to hypoxia was significantly lower in parkinsonian patients taking dopaminergic medications than in controls. Patients who received no dopaminergic medication had significantly lower HVR than controls. Interestingly, the degree of impairment in HVR of patients without dopaminergic medication was similar to that of patients taking these drugs. These results clearly show that Parkinson's disease itself impairs the chemosensitivity to hypoxia. Dopaminergic drugs at the doses commonly used to treat patients with Parkinson's disease might not, therefore, impair further the HVR in patients with Parkinson's disease. Investigation would be useful of whether dopamine receptor antagonists that do not cross the blood-brain barrier could have a beneficial effect on HVR in patients with Parkinson's disease.2 As Röggla and colleagues mention a study is needed of whether patients with Parkinson's disease have a higher risk of respiratory disorders or sudden death in conditions than non-parkinsonian patients when hypoxia is induced, for example, while flying or at high altitude.

The impaired HVR in Parkinson patients cannot be explained solely by a dysfunction of the dopaminergic system. If only dopaminergic systems in the carotid body were damaged in Parkinson's disease, patients would have higher HVR than controls.1 and 2 We must take into account the possibility that other neurotransmitter systems commonly affected in Parkinson's disease, such as serotonergic or noradrenergic systems, play a critical part in the impaired HVR.3

http://www.sciencedirect.com/science...f66f6aac8aa8d6

Annals of the New York Academy of Sciences 939:33-44 (2001)
© 2001 New York Academy of Sciences

Lack of Protective Effect by Intermittent Hypoxia on MPTP-Induced Neurotoxicity in Mice

GIN-HEUY LAIa, CHAU-FONG CHENb, YU SUc, LOW-TONE HOa AND ANYA MAAN-YUH LINa,c

In contrast to acute ischemia and subsequent reperfusion that produce excess free radicals, intermittent hypoxia (IH) is reported to play an important role in upregulation of antioxidative defensive mechanisms. In the study we report here, the neuroprotective effect of IH was evaluated using intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in ICR mice. Adult male ICR mice were subjected to 380 mmHg in an altitude chamber for 15 hours/day for 14 or 28 days. MPTP decreased striatal dopamine content in normoxic mice.

However, IH did not significantly alter the MPTP-induced depletion of striatal dopamine content. Furthermore, MPTP had no effect on GSH content but reduced GSH/GSSG ratio in mouse striatum. IH altered neither GSH content nor MPTP-induced reduction in GSH/GSSG ratio. Although MPTP had no effect on striatal SOD activity in normoxic mouse, IH increased SOD activity in the saline and MPTP groups. Neither MPTP nor IH affected GPx in mouse striatum.

Furthermore, in our ex vivo study, both the autooxidation and iron induced lipid peroxidation of cortical homogenates were lower in the IH-treated group than those of the normoxic group, indicating a reduced oxidative status after IH treatment.

In conclusion, exposure to IH has been suggested to be beneficial in preventing iron-induced oxidative injuries in biological organisms, and our data support this notion in that IH not only decreased iron-induced lipid peroxidation but also increased antioxidative defense enzyme activity in mouse brain.

Furthermore, the lack of neuroprotective effect by IH of MPTP-induced depletion of striatal dopamine content suggests that oxidative stress may not be the only mechanism for the MPTP-induced neurotoxicity.

Intermittent hypoxia (IH) improves hypoxic ventilatory sensitivity and blood dopamine (DA) in patients with parkinson's disease (PD)


Abstract:

DA takes part in respiratory control system as a neurotransmitter in carotid bodies and central structures. Adaptation to IH produces enhanced hypoxic ventilatory responses (HVR) in healthy humans.

This study tested the hypothesis that decreased HVR in PD patients is associated with disturbances in DA metabolism which could be improved by IH training. 18 healthy young (23+/-2 yr: G1), 17 healthy old (60+/-1.4 yr: G2) males, and 18 PD patients (59+/-2.1 yr: G3) were studied before and after 15 days of IH.

Before training, HVR in G3, when compared to G2 and G1, was 24% and 42% lower, venous blood DA content was 26% and 73% higher, and precursor DOPA content was 98% and 460% higher, respectively.

IH training provoked a doubling in HVR in both G1 and G2, and increase by 250% in G3. This increased HVR was accompanied by augmentation of DA/DOPA in G1 (24% and 190%, respectively), and monoamines reduction in G2 (by 29% and 40%, respectively) and G3 (by 66% and 34%, respectively).

Thus, IH training normalized the hypoxic ventilatory sensitivity in PD patients and approached blood DA/DOPA level to healthy subjects. We suggest that the relationships between HVR and reciprocal DA/DOPA values in associated with age decrease of DA receptor sensitivity and an enhance DA reuptake during IH traning.

http://www.ingentaconnect.com/conten...00001/art81209

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Fiziol Zh. 2003;49(3):95-103.

[Respiratory regulation during adaptation to intermittent hypoxia in patients with Parkinson disease]

[Article in Ukrainian]

Serebrovs'ka TV, Kolesnikova IeE, Karaban' IM.

Bogomoletz Institute of Physiology, Institute of Gerontology, Kiev, Ukraine.

Ventilatory responses to hypoxic (HVR) and hypercapnic (HCVR) stimuli in relation with dopamine (DA) and DAs precursor dihydroxy phenylalanine (DOPA) venous blood content were studied in healthy people aged 55-65 years (Gr. 1) and Parkinson's disease (PD) patients without (Gr. 2) and with (Gr. 3) L-DOPA treatment under intermittent hypoxic training (IHT, three identical daily isocapnic, progressive, hypoxic rebreathing sessions separated by 5-minute breaks for 14 consecutive days). HVR in Gr. 2, when compared to Gr. 1, was 48% lower showing almost linear dependence and was accompanied by lower levels of blood DOPA and DA content (26% and 20%, respectively). HVR in Gr. 3 was only 17% lower compared to Gr. 1 and was accompanied by higher levels of blood DOPA and DA content (40% and 147%, respectively). No differences in HCVR between groups were registered. IHT produced a 75% increase in HVR in Gr. 1 (p < 0.05), 52% augmentation of HVR in Gr. 2 (p < 0.05, at that the curves became hyperbolic in shape), and 2.2-fold increase in Gr. 3 (p < 0.01). The augmentation of hypoxic sensitivity under IHT was accompanied by significant decrease in DOPA blood concentration in Gr. 1 and Gr. 3, although no changes in Gr. 2 were observed. It was no changes in DA blood content in all groups. IHT produced no significant changes in HCVR.

This investigation confirms the conception that PD is accompanied by DA deficit not only in basal ganglia but also in peripheral chemoreceptors provoking a decrease in hypoxic ventilatory sensitivity. PD does not influence on hypercapnic sensitivity. L-DOPA-treatment as well as IHT improve the functioning of respiratory system, increase HVR and do not influence on HCVR. The method of IHT can be involved in complex therapy of PD.