Multinuclear NMR Studies on the Energy Metabolism of Glial and Neuronal Cells

Abstract

In this multinuclear NMR study myo-inositol is identified as a glia-specific marker for in vivo NMR studies. The unusually high inositol concentration may participate in the osmoregulatory system in asupcytes. Primary astrocytes also synthesize and export high amounts of hypotaurine, an intermediate of taurine synthesis. Taurine – another osmolyte – is synthesized from cysteine by astrocytes but not by primary neurons. Taurine as well as hypotaurine is accumulated by neurons from the extracellular medium. ¹³C NMR labelling results with 2-¹³C pyruvate indicate a considerable contribution of the anaplerotic pathway in primary neurons from rat. The activity is only half of the activity in primary astrocytes. The ratio of pyruvate carboxy-lase/malic enzyme activity versus pyruvate dehydrogenase activity reflects the degree of maturation. The ¹³C isotopomer ratio of glutamate and glutamine is different for pure astrocyte cultures. Therefore, the different isotopomer ratios of glutamate to glutamine obtained from intact brain studies alone do not prove TCA cycle compartimentation in the brain. Finally, the PCr/ATP ratio in primary astrocytes is 3 times higher than in primary neurons. This has to be considered in case of recovery from ischemic insults.

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H‐MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

“…Another explanation is that the [Cr] corr increase is a general phenomenon associated with the gliosis often co-existing with brain atrophy at the neuropathological examination in patients with degenerative diseases of the CNS (27). This explanation is in line with the observations that [Cr] is higher in astrocytes than in neurons (28,29) and that neurodegeneration suggests death of NAA containing neurons which are partially substituted by proliferation of glial cells. This hypothesis was purported in a prior study in patients with ataxia (23) but needs to be further investigated.…”

IMPA1 is Essential for Embryonic Development and Lithium-Like Pilocarpine Sensitivity

“…The fact that the adult IMPA1 À/À mice did not show reduced inositol levels in various brain regions does not rule out inositol depletion as a mechanism of the observed seizures. Several pools of inositol are suggested to exist in the brain (Bersudsky et al, 1994;Brand et al, 1993;Fisher et al, 2002;Frey et al, 1998;Novak et al, 1999Novak et al, , 2000a and the IMPA1-dependent inositol pool likely makes up only a small, possibly spatially delineated but clearly significant part. Actually, inositol depletion as a result of dietary inositol restriction (Shaldubina et al, 2006b) or hyponatremia (Bersudsky et al, 1994) has been shown not to sensitize pilocarpine-induced seizures.…”

Metabonomic analysis identifies molecular changes associated with the pathophysiology and drug treatment of bipolar disorder

“…Myo-inositol is a significant intracellular osmolyte, and the changes may indicate alterations in tissue osmolarity. 21,43 Additionally, the metabolite is known to be more abundant in glia than in neurons, 44 and the change may thus suggest neuronal atrophy in the disorder and a shift in the neuronal/glial balance toward neuronal cells with mood stabilizer treatment.…”