This project has continued to examine the reciprocal relationship which has been found to exist between neurons and the surrounding astroglial cells. This relationship involves metabolic trafficking which not only supplies neurons with products such as lactic acid which can be used for energy production, but also products which serve an essential anaplerotic role in the neuronal cells. These products are formed in the astroglial cells either as a result of CO2 fixation, oxidative metabolism or glycolytic metabolism.Using 14CO2 as a precursor, we have followed the formation and release of products from astroglial cells and have found that there is marked selectivity in which products are retained and which are released. For example,newly synthesized glutamine is promptly released into the extracellular fluid (ECF) whereas newly synthesized glutamate is mostly retained within the astroglial cell. The hypothesis underlying metabolic trafficking is that metabolic intermediates are being released from the glial cells in response to a signal or signals from nearby neurons. One of these signals may be the potassium concentration in the ECF. This concentration can increase several fold when neurons are stimulated either normally or abnormally. We have found that changes in the ECF potassium concentration can either increase or decrease the formation and the release of the astroglial products included in this study. This provides an important link between neuronal activity, the resulting metabolic requirements of the neurons and the metabolism of the surrounding astroglial cells. Astroglial cells have been found to utilize glucose at a much more rapid rate than neurons. The rate of glycolysis in astroglial cells is high; over ninety percent of the glucose taken up by these cells is converted to lactate .Only a small percent of the glucose is converted to carbon dioxide and water in the astroglial cells .Although neurons do not convert glucose to lactate at a rapid rate they have been found to oxidize both glucose and lactate to carbon dioxide and water at a much more rapid rate than do the astroglial cells. Neurons are therefore capable of oxidizing the lactate formed in the astroglial cells ; there is evidence to suggest that they may have a preference for lactate when presented with both lactate and glucose.These data present a second example of metabolic trafficking between neurons and astroglia. D-beta-Hydroxybutyrate , a substrate of importance to newborn animal , has been found to be oxidized to carbon dioxide and water by both neurons and astroglia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002414-11
Application #
6111144
Study Section
Special Emphasis Panel (LCM)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code