Abstract
Ever since it was shown for the first time that lactate can support neuronal function in vitro as a sole oxidative energy substrate, investigators in the field of neuroenergetics have been debating the role, if any, of this glycolytic product in cerebral energy metabolism. Our experiments employed the rat hippocampal slice preparation with electrophysiological and biochemical methodologies. The data generated by these experiments (a) support the hypothesis that lactate, not pyruvate, is the end-product of cerebral aerobic glycolysis; (b) indicate that lactate plays a major and crucial role in affording neural tissue to respond adequately to glutamate excitation and to recover unscathed post-excitation; (c) suggest that neural tissue activation is accompanied by aerobic lactate and NADH production, the latter being produced when the former is converted to pyruvate by mitochondrial lactate dehydrogenase (mLDH); (d) imply that NADH can be utilized as an endogenous scavenger of reactive oxygen species (ROS) to provide neuroprotection against ROS-induced neuronal damage.
Highlights
Almost a quarter of century ago we demonstrated for the first time the ability of cerebral tissue in vitro to sustain normal neuronal function by utilizing lactate aerobically as its sole energy substrate (Schurr et al, 1988)
Slices in paradigm A were exposed to a lower Glut concentration (5 mM) than slices in paradigm B (20 mM), since the higher the glucose concentration in the aCSF, the higher Glut concentration slices could tolerate and the higher the level of lactate slices could produce during exposure to Glut
Less than 10% of the slices showed recovery of neuronal function when supplied with 10 mM glucose and exposed to 20 mM Glut for 15 min
Summary
Almost a quarter of century ago we demonstrated for the first time the ability of cerebral tissue in vitro to sustain normal neuronal function by utilizing lactate aerobically as its sole energy substrate (Schurr et al, 1988). For many who still hold that lactate is the end-product of anaerobic glycolysis, it is difficult to visualize this monocarboxylate as a major player in cerebral energy metabolism. The findings of Pellerin and Magistretti (1994) and the hypothesis they have offered to explain them, i.e., the astrocytic-neuronal lactate shuttle hypothesis (ANLSH), have been supported by many studies over the years (Hu and Wilson, 1997a; Schurr et al, 1997a,b, 1999a,b; Mangia et al, 2003; Kasischke et al, 2004; Schurr, 2006; Atlante et al, 2007; Schurr and Payne, 2007; Larsen et al, 2008; Passarella et al, 2008; Gallagher et al, 2009). The prevailing assumption of those who discount the role of lactate is that as long as there are sufficient supplies of oxygen and glucose, glycolysis should produce enough pyruvate to satisfy the heightened energy demands upon activation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
