The Appearance of the Warburg Effect in the Developing Avian Eye Characterized In Ovo: How Neurogenesis Can Remodel Neuroenergetics

Abstract

The avian eye is an established model for exploring mechanisms that coordinate morphogenesis and metabolism during embryonic development. Less is known, however, about trafficking of bioenergetic and metabolic signaling molecules that are involved in retinal neurogenesis. METHODS. Here we tested whether the known 3-day delayed neurogenesis occurring in the pigeon compared with the chick was associated with a deferred reshaping of eye metabolism in vivo. Developmental metabolic remodeling was explored using 1 Hmagnetic resonance spectroscopy of the whole eye and vitreous body, in ovo, in parallel with biochemical and molecular analyses of retinal, vitreous, and lens extracts from bird embryos. RESULTS. Cross-species comparisons enabled us to show that a major glycolytic switch in the retina is related to neurogenesis rather than to eye growth. We further show that the temporal emergence of an interlocking regulatory cascade controlling retinal oxidative phosphorylation and glycolysis results in the exchange of lactate and citrate between the retina and vitreous. CONCLUSIONS. Our results point to the vitreous as a reservoir and buffer of energy metabolites that provides trophic support to oxidative neurons, such as retinal ganglion cells, in early development. Through its control of key glycolytic regulatory enzymes, citrate, exchanged between extracellular and intracellular compartments between the retina and vitreous, is a key metabolite in the initiation of a glycolytic switch.

Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

“…Recently, Cherix et al (2020) demonstrated the existence of a glycolytic switch in the in ovo avian retina related to neurogenesis. This study also illustrated how neurogenesis can remodel neuroenergetics and showed the value of MRS in this instance.…”

“…For example, Koush et al (2019) showed that j-edited fMRS at 4 T demonstrated good sensitivity and specificity for task-induced lactate modulation as well as for a smaller peak at 1.28 ppm in the motor cortex. These methodological developments could be useful for in vivo evaluation of the accumulated changes in lactate seen in other studies on neurogenesis (Prevot et al, 2018;Cherix et al, 2020).…”

Increased neuron density in the midbrain of foveate birds results from profound change in tissue morphogenesis

“…In precocial Galloanserae, the need for a functional visual system at the time of hatching requires the production of RGCs at early stages, thereby de facto limiting their number. In pigeon, high level of retinoic acid and robust mitochondrial activity contribute to maintain retinal progenitors in proliferation, thereby prolonging their uncommitted status (Brodier et al, 2021; Cherix et al, 2020; Rodrigues et al, 2016). At the end of neurogenesis, the density of newborn RGCs is about three times higher in pigeon than in chicken.…”

Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

“…Brain was extracted, DH was removed, frozen on liquid nitrogen and stored at −80 °C. Samples were then ground on mortar using liquid nitrogen, weighed and followed by a CHCl 3 /MeOH Folch-Pi extraction [ 36 , 37 ]. Samples were stirred at 4 °C in a 1:1:1 mixture of CHCl 3 :MeOH:H 2 O for 30 min after what the aqueous phase was collected and lyophilized.…”