The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes.

No abstract

Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. In normal situations, cells are protected against methylglyoxal toxicity by different mechanisms and in particular the glyoxalase system, which represents the most important pathway for the detoxification of methylglyoxal. While the neurotoxic effects of methylglyoxal and AGEs are well characterized, our understanding the glyoxalase system in the brain is more scattered. Considering the high energy requirements (i.e., glucose) of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regard to its activity in astrocytes and neurons. A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.

Amyloid-␤(A␤)peptidesplayakeyroleinthepathogenesisofAlzheimer'sdiseaseandexertvarioustoxiceffectsonneurons;however,relatively littleisknownabouttheirinfluenceonglialcells.Astrocytesplayapivotalroleinbrainhomeostasis,contributingtotheregulationoflocalenergy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of A␤ peptides on glucose metabolism in cultured astrocytes. Following A␤ 25-35 exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. A␤ increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of A␤ on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by A␤ impair neuronal viability. The effects of the A␤ 25-35 fragment were reproduced by A␤ 1-42 but not by A␤ 1-40 . Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that A␤ aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.

1. The aim of this study was to document the kinematics and the electromyographic activity recorded from several muscles during treadmill locomotion in the same cat (N = 4), before and after spinalization by using a chronic implantation method. Because identical experimental and control conditions were used, it was possible to establish similarities and differences in the timing and amplitude of the muscular activity and kinematics under the intact and spinal conditions in the same animal. The data presented in this paper were collected when the cats had fully recuperated a stable locomotor pattern, walking at a constant speed of approximately 0.4 m/s. 2. The adult spinal cats retained many of the general locomotor features and electromyographic (EMG) characteristics seen before transection. However, there were also important differences. 3. There was a reduction in the step length that was principally due to the forward placement of the paw at the onset of the stance. Similarly, there was a decrease in the step cycle duration which was attributed to a reduction of both the stance and swing phases. 4. The overall angular excursions of the hip, knee, and ankle were generally similar, although joints were sometimes more flexed at all phases of the step cycle. In contrast, the overall excursions of the metatarsophalangeal joints was much greater in all four cats after spinalization due to a paw drag during the initial portion of the swing phase that exaggerated the plantarflexion. 5. There was an increase in the EMG amplitude of the flexor muscles at two of three joints (i.e., hip, knee, and ankle) in each cat after spinalization. The change in the EMG amplitude of the extensors did not appear to be as consistent as that observed in the flexor muscles. When looking at each cat individually, the postspinalization extensor activity decreased at two of three joints in two cats, whereas the opposite was true for the other two cats. 6. There was a delay in the onset of the knee flexor (semitendinosus) activity while the ankle dorsiflexor (tibialis anterior) activity started earlier with respect to the beginning of the swing phase. The onset of hip flexors was somewhat more variable. This change in the timing of flexor activity was most probably responsible for the paw drag at the onset of the swing phase. 7. The present results reveal that despite the few differences, the spinal cord and the hindlimbs afferents are capable of generating very good locomotor patterns with almost normal kinematics and EMG characteristics.