Yes, that’s the one. It’s written very broadly with each chapter reading like a review paper. It felt a bit repetitive at times; multiple chapters conclude by calling for more studies to be done, but I suppose that’s expected. I was surprised that it didn’t have much discussion related to free diving as I would think many papers would have been done in that area related to hypoxia. I feel like to get more out of the book, you’d need to find and read some of the studies on specific topics of interest. Overall, it’s good and I enjoyed it and I may re-read it at some point.
Parkinson’s disease (PD) is characterized by inclusions of α-synuclein (α-syn) and mitochondrial dysfunction in dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). Patients with PD anecdotally experience symptom improvement at high altitude; chronic hypoxia prevents the development of Leigh-like brain disease in mice with mitochondrial complex I deficiency. Here we report that intrastriatal injection of α-syn preformed fibrils (PFFs) in mice resulted in neurodegeneration and movement disorder, which were prevented by continuous exposure to 11% oxygen. Specifically, PFF-induced α-syn aggregation resulted in brain tissue hyperoxia, lipid peroxidation and DA neurodegeneration in the SNpc of mice breathing 21% oxygen, but not in those breathing 11% oxygen. This neuroprotective effect of hypoxia was also observed in Caenorhabditis elegans. Moreover, initiating hypoxia 6 weeks after PFF injection reversed motor dysfunction and halted further DA neurodegeneration. These results suggest that hypoxia may have neuroprotective effects downstream of α-syn aggregation in PD, even after symptom onset and neuropathological changes.
Because our RNA-seq and proteomics results showed upregulation of several HIF-dependent genes in the SN of mice breathing 11% O2, it is possible that the beneficial effects of hypoxia breathing are partially mediated via HIF-dependent mechanisms. Alternatively, it is also conceivable that chronic continuous hypoxia breathing prevents and reverses the progression of PD pathology through distinct mechanisms (for example, mitigating brain tissue hyperoxia) from intermittent hypoxia breathing. Our current study provides timely evidence showing robust neuroprotective effects of chronic continuous hypoxia breathing in a mouse model of PD induced by a templated conversion of endogenous α-syn to inclusions. Because chronic continuous hypoxia has been shown to be beneficial also in mouse models of Friedreich’s ataxia41, multiple sclerosis52 and premature aging53, it is likely to be broadly neuroprotective via multiple mechanisms. Further preclinical studies are needed to determine the safety and efficacy of chronic hypoxia breathing, including the optimal concentrations of hypoxic gas mixtures, longer durations of exposure and the effects of hypoxia at different disease stages. These results motivate more research into the effects of chronic continuous hypoxia breathing42, or pharmacological strategies that reduce oxygen delivery54, potentially leading to new therapeutic strategies to prevent and even halt the progression of PD.