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中国神经科学学会第十二届全国学术会议

作者： klaus-armin nave Max Planck Institute of Experimental Medicine

Myelin is the multilayered membrane ensheathment of axons, made by oligodendrocytes and Schwann cells, which enables rapid saltatory impulse propagation. However, myelin also deprives the insulated axonal compartment from the outside milieu and thus from rapid access to essentual metabolites, such as glucose. Thus for fastspiking axons with elevated energy consumption the myelin architecture poses a potential metabolic problem. In different mouse mutants with oligodendrocyte defects, we found that oligodendrocytes are required for both myelination and the survival of axons. In fact, two cellular functions in myelination and in axon support can be genetically uncoupled in different mutant mice. Recently, we discovered an underlying mechanism, by which oligodendroytes provide lactate to the axonal compartment for the generation of ATP. Trying to understand how lactate supply is matched to the real axonal energy needs, which can differ widely, we noticed that activation of oligodendroglial NMDA receptors（as a proxy for axonal spiking activity） causes the rapid redistribution of the glucose transporter GLUT1 and enhanced glucose import. In mice lacking oligodendroglial NMDA receptors, functional GLUT1 expression in the myelin compartment is reduced, which perturbs axon conduction, most visibly under metabolic stress and at higher spiking frequency. Reduced axonal ATP levels can be measured real time when using transgenic mice with neuronally expressed metabolic sensors. Loss of metabolic support by oligodendrocytes is likely a contributing factor for a range of myelin diseases, and is also relevant for neurodegenerative diseases, since long axons are a bottle neck of neuronal integrity.

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Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress

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Neuroprotection 2023年第1期1卷 9-19页

作者： Hannelore Ehrenreich Max Gassmann Luise Poustka Martin Burtscher Peter Hammermann PhD Anna-Leena Sirén klaus-armin nave Kamilla Miskowiak Clinical Neuroscience Max Planck Institute for Multidisciplinary SciencesGöttingenGermany Institute of Veterinary Physiology and Zürich Center for Integrative Human Physiology University of ZürichZürichSwitzerland Department of Child and Adolescent Psychiatry and Psychotherapy University Medical Center GöttingenGöttingenGermany Faculty of Sports Science University of InnsbruckInnsbruckAustria HBL Investmentpartners GmbH München‐FrankfurtGermany Departments of Neurophysiology and Neurosurgery University of WürzburgWürzburgGermany Department of Neurogenetics Max Planck Institute for Multidisciplinary SciencesGöttingenGermany Psychiatric Centre Copenhagen University HospitalRigshospitaletCopenhagenDenmark Department of Psychology University of CopenhagenCopenhagenDenmark

Hypoxia is increasingly recognized as an important physiological driving force.A specific transcriptional program,induced by a decrease in oxygen(O2)availability,for example,inspiratory hypoxia at high altitude,allows cells to adapt to lower O2 and limited energy *** transcriptional program is partly controlled by and partly independent of hypoxia-inducible ***,this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise,leading to a relative decrease in O2 supply,compared to the acutely augmented O2 *** have coined the term“functional hypoxia”for this important demand-responsive,relative reduction in O2 *** hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial“brain hardware upgrade,”underlying advanced ***-induced erythropoietin expression in the brain likely plays a decisive role in these processes,which can be imitated by recombinant human erythropoietin *** article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain *** thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain ***,it sketches a planned multistep pilot study in healthy volunteers and first patients,about to start,aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.

关键词： brain EPO circle erythropoietin functional hypoxia HIF human pilot study hyperoxia inspiratory oxygen manipulations motor-cognitive performance PBMC translation

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