Functional relationship of ammonia to DNA, RNA and protein in brain

Abstract

The functional significance of the production of ammonia during neuronal activity is not known, although a number of studies are available concerning the mechanism of ammonia toxicity in brain. Hyperammonemia without behavioural change was induced in experimental rats by i.p. administration of either a single dose of ammonium acetate or 6 doses with an interval of 1 h during the day or one single dose daily for 7 days. No significant change was observed in the content of DNA, RNA and protein in cerebral cortex, cerebellum and brain stem following the administration of a single dose. There was a marked decrease in the content of DNA in all three brain regions after the administration of 6 hourly doses of ammonium acetate. Under these conditions the RNA was found to increase in all three brain regions. A decrease in the content of protein per gram wet weight was observed in cerebral cortex and brain stem while the change in cerebellum was found to be insignificant. However, the content of RNA and protein was found to show a very significant increase when expressed per microgram of DNA for each region under these conditions, indicating an increase in RNA and protein in the cells surviving the toxic damage caused by ammonia. A marked and significant increase in the content of RNA and protein was observed in all three brain regions following the administration of a single dose per day for 7 days. These results are discussed not only with respect to toxic damage to the glial cells by ammonia, but also with respect to the probable effect of ammonia liberated during neuronal activity on inhibition of lysosomal degradation of protein, and on its stimulatory effects of transcriptional and translational activities. The increased RNA and protein under these conditions may be contributing not only in the proliferation of glial cells (Alzheimer Type II cells) but also in the dendritic spinous growth.