Glial cells and metabolic compartmentation / S. Berl, W.J. Nicklas, and D.D. Clarke Dept. of Neurology, MT. Sinai School of Medicine, N.Y., N.Y. 10029 Dept. of Chemistry, Fordham University, N.Y. 10458, U.S.A.

Abstract

The study of metabolic compartmentation in brain has been under investigation for some twenty years. Most interpretations of the data have focused on attempts to assess the relative contributions of glia and neurons to the metabolic pictures since anatomically and functionally they are distinct. It is very probable that these cell types contain other metabolic compartments based on anatomic and subcellular subdivisions. However, the presently available experimental data is insufficient to specify precisely the total number of such metabolic pools functioning in nervous tissue. The initial observations that set in motion most of the work were a) in the adult animal there is a very marked blood-brain barrier to glutamate, and b) labelled glutamate administered intracranially is converted to glutamine much more rapidly than it mixes with the total glutamate endogenous to the brain. This results in a radiospecific activity of isolated glutamine several times that of its precursor glutamate even at time periods of a few minutes. This characteristic phenomenon could also be elicited with other labelled substrates e.g. aspartate as well as by peripheral administration of labelled substrates which more readily enter the brain from the circulation such as acetate, leucine, bicarbonate and ammonium salts. These in vivo studies were confirmed by in vitro studies which allow greater experimental manipulation. One of the ways of studying these compartments and determining their physiological importance is to perturb the normal metabolic state and attempt to relate the subsequent alterations in metabolic flux of labelled tracers to hypothesis of compartment localizatio