Albumin promotes neuronal survival by increasing the synthesis and release of glutamate

Abstract

It is well known that the presence of albumin within the brain and the CSF is developmentally regulated. However, the physiological relevance of this phenomenon is not well established. We have previously shown that albumin specifically increases the flux of glucose and lactate through the pyruvate dehydrogenase reaction in astrocytes. Here we show that, in neurones, albumin also increases the oxidation of glucose and lactate through the pyruvate dehydrogenasecatalysed reaction, the final purpose of this being the synthesis of glutamate. Thus, in neurones, the presence of albumin strongly increased the synthesis and release of glutamate to the extracellular medium. Our results also suggest that glutamate release caused by albumin is designed to promote neuronal survival. Thus, under culture conditions in which neurones die by apoptosis, the presence of albumin promoted neuronal survival and maintained the differentiation programme of these cells, as judged by the expression of the axonal protein, GAP-43. The effect of albumin on neuronal survival was counteracted by the presence of DNQX, an antagonist of non-NMDA-glutamate receptors, suggesting that the glutamate synthesized and released due to the presence of albumin is responsible for neuronal survival. In addition, the effect of albumin seemed to depend on the activity of the NGF receptor, TrkA, suggesting that the glutamate synthesized and released due to the presence of albumin promotes neuronal survival through the activity of TrkA.

Uteroplacental Inflammation Results in Blood Brain Barrier Breakdown, Increased Activated Caspase 3 and Lipid Peroxidation in the Late Gestation Ovine Fetal Cerebellum

“…Many Purkinje cells were also immunopositive for albumin. It has been shown that Purkinje cells are particularly prone to sequestering albumin [28] , which may be a protective response and an attempt to abrogate or forestall apoptosis [29] . Given that Purkinje cells form a population of cells that, after a certain time in development are not replaced, a deficit in these cells may result in significant life-long functional deficits.…”

Cerebrovascular Responses in the Fetal Sheep Brain to Low-Dose Endotoxin

“…Whereas in situ synthesis of albumin by neurons and blood-to-brain transfer of plasma proteins are processes present in the immature brain, these are not present in the fetal sheep brain after approximately 120 d gestation (40). Albumin uptake has been observed in cultured neurons, where it appears to influence glucose utilization, increase glutamate synthesis, and suppress apoptosis, suggesting that it promotes neuronal survival (41).…”

Albumin synthesis in preterm infants on the first day of life studied with [1-13C]leucine

“…Albumin's numerous functions include maintenance of colloid osmotic pressure (accounting for ϳ80%), buffering, and transport of bilirubin, uremic toxins, porphyrins, fatty acids, metals, cortisol, thyroxine, endotoxins, medications, and endogenous nitric oxide. Furthermore, it is thought to be an important antioxidant and as such could play a role in neuronal survival during development (42). These functions are of vital importance to the critically ill preterm neonate.…”