Neuronal cultures in vitro readily oxidized both D-[ 14 C]glucose and L-[14C]lactate to 14 CO2, whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [ 14 C]Glucose oxidation to 14 CO2 varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [ 14 C]lactate oxidation to 14 CO2 only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvate͞ lactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO2 and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mg͞kg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMRglc). Dichloroacetate raised baseline lCMRglc throughout the brain and decreased the percent increases in lCMRglc evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.G lucose is an essential and normally almost exclusive substrate for cerebral energy metabolism (1). As in other tissues, it is metabolized in brain in two sequential pathways, first to pyruvate͞lactate by glycolysis in cytosol, followed by oxidation in mitochondria to CO 2 and H 2 O. It was recently proposed that the glycolytic and oxidative components of glucose and glycogen metabolism are compartmentalized not only between cytosol and mitochondria but also between astroglia and neurons, i.e., glucose and glycogen metabolism in astroglia to lactate, which is then exported to neurons where it is oxidized to provide the ATP needed for neuronal function (2, 3). Arguments in support of this hypothesis are: (i) capillaries in brain are largely enveloped by astroglial processes that present a barrier to the transport of glucose from blood to neurons; (ii) glycogen in brain is confined almost entirely to astrocytes; (iii) astrocytes in culture readily metabolize glucose to lactate and release it into the medium (4, 5); and (iv) glutamate, the most prevalent excitatory neurotransmitter in brain, stimulates aerobic glycolysis in cultured astrocytes (6, 7). Much of the evidence suppo...
There is growing evidence that serotonin (5-hydroxtryptamine, 5-HT) has major influences on brain development in mammals.
A 74-year-old woman presented with malignant progression of remnant epidermoid cyst manifesting as sudden onset of right ptosis and double vision. She had right oculomotor nerve paresis. She had a history of surgery for right cerebellopontine angle epidermoid cyst 20 years previously. T 1 -weighted magnetic resonance (MR) imaging demonstrated a hypointense mass lesion in the right cerebellopontine angle and basal cistern, and an isointense mass in the right paraclinoid region which was strongly enhanced. Diffusion-weighted MR imaging showed hyperintense areas in the right cerebellopontine angle, ambient cistern, and basal cistern, and the paraclinoid mass as hypointense. Surgery was performed using Dolenc's approach. Histological examination revealed that the paraclinoid tumor adjacent to the epidermoid tumor remnant was malignant transformation of epidermoid cyst into squamous cell carcinoma. She was treated with 46 Gy linac radiotherapy. She has been without tumor recurrence for 17 months. Malignant change of epidermoid cyst is extremely rare, but rapid progress of the symptoms suggests malignant transformation. MR imaging with gadolinium is useful for diagnosis.
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