High Levels of Ascorbic Acid, Not Glutathione, in the CNS of Anoxia‐Tolerant Reptiles Contrasted with Levels in Anoxia‐Intolerant Species

Abstract

Ascorbic acid and glutathione (GSH) are antioxidants and free radical scavengers that provide the first line of defense against oxidative damage in the CNS. Using HPLC with electrochemical detection, we determined tissue contents of these antioxidants in brain and spinal cord in species with varying abilities to tolerate anoxia, including anoxia‐tolerant pond and box turtles, moderately tolerant garter snakes, anoxia‐intolerant clawed frogs (Xenopus laevis), and intolerant Long‐Evans hooded rats. These data were compared with ascorbate and GSH levels in selected regions of guinea pig CNS, human cortex, and values from the literature. Ascorbate levels in turtles were typically 100% higher than those in rat. Cortex, olfactory bulb, and dorsal ventricular ridge had the highest content in turtle, 5–6 µmol g−1 of tissue wet weight, which was twice that in rat cortex (2.82 ± 0.05 µmol g−1) and threefold greater than in guinea pig cortex (1.71 ± 0.03 µmol g−1). Regionally distinct levels (2–4 µmol g−1) were found in turtle cerebellum, optic lobe, brainstem, and spinal cord, with a decreasing anterior‐to‐posterior gradient. Ascorbate was lowest in white matter (optic nerve) in each species. Snake cortex and brainstem had significantly higher ascorbate levels than in rat or guinea pig, although other regions had comparable or lower levels. Frog ascorbate was generally in an intermediate range between that in rat and guinea pig. In contrast to ascorbate, GSH levels in anoxia‐tolerant turtles, 2–3 µmol g−1 of tissue wet weight, were similar to those in mammalian or amphibian brain, with no consistent pattern associated with anoxia tolerance. GSH levels in pond turtle CNS were significantly higher (by 10–20%) than in rat for several regions but were generally lower than in guinea pig or frog. GSH in box turtle and snake CNS were the same or lower than in rat or guinea pig. The distribution GSH in the CNS also had a decreasing anterior‐to‐posterior gradient but with less variability than ascorbate; levels were similar in optic nerve, brainstem, and spinal cord. The paradoxically high levels of ascorbate in turtle brain, which has a lower rate of oxidative metabolism than mammalian, suggest that ascorbate is an essential cerebral antioxidant. High levels may have evolved to protect cells from oxidative damage when aerobic metabolism resumes after a hypoxic dive.

Illustrated Review of the Embryology and Development of the Facial Region, Part 3: An Overview of the Molecular Interactions Responsible for Facial Development

“…Once these and other remaining questions are answered and there is a more complete understanding of the molecular changes involved in normal facial development, how and why facial malformations occur and how they may possibly be prevented will be better understood. 1,9,10 …”

“…The control of these outgrowths is by epithelial- mesenchymal interactions, and it is primarily the mesenchymal signaling that controls the outgrowth. 9 In addition to retinoic acid, 5 key families of secreted growth factors have been identified that control facial outgrowth via regulation of cell proliferation and survival. These factors include fibroblast growth factors, transforming growth factor ␤ and bone morphogenetic proteins, sonic hedgehog, Wnts, and endothelin-1 (ET-1).…”

“…On the other hand, antagonistic signaling interactions between Fgf8 and BMP4 outline the boundaries of gene expression for a number of homeobox-containing genes, and this can determine the position of the odontogenic field and odontogenic patterning. 1,9 In addition, retinoic acid, Fgf, and BMP are responsible for controlling Shh and overall facial outgrowth. 11 In general, signaling is subject to precise spatial and temporal control: Too much or too little genetic input or input out of the regulated normal temporal sequence results in abnormalities.…”

“…Tables 5 and 6 list some of the gene mutations associated with a cleft palate with and without a cleft lip in humans. 1,9 If any of the above normal signaling does not occur, a cleft palate can occur either as an isolated entity or in combination with a cleft lip, and there are Ͼ300 syndromes in which such clefts are associated-that is, clefts occur when there are abnormalities in the normal process of development.…”

Essential Role of Ascorbic Acid in Neural Differentiation and Development: High Levels of Ascorbic Acid 2-Glucoside Effectively Enhance Nerve Growth Factor-Induced Neurite Formation and Elongation in PC12 Cells

“…[1][2][3][4][5] Therefore, AsA is predicted to play a critical role in the formation and maintenance of the neural microenvironment. Several studies have demonstrated that AsA acts as an antioxidant in the brain and has neuroprotective effects in models of cerebral ischemia.…”