Functional relationship between ammonia and gangliosides in brain

Abstract

The functional significance of ammonia production in brain under physiological or pathological conditions is not clearly known. NH4+ stimulates Na+, K+ activated ATPase causing stabilization of neuronal membranes of which gangliosides are major structural components. Moreover ammonia is known to inhibit lysosomal enzymes which include enzymes degrading gangliosides. Gangliosides have been shown to stimulate neuritogenesis in neuronal cultures and prevent the damage of the neurons from glutamate toxicity particularly in areas of brain ischemia. Hyperammonemia without any behavioural changes was induced in experimental rats by intraperitoneal administration of either a single dose (0.8 mmol/100 g wt.) or by six 'hourly' doses (0.6 mmol/100 g wt.) of ammonium acetate. An increase in the content of gangliosides along with a rise in the content of GD1A and GD1B without any change in beta-galactosidase and N-acetylhexosaminidase was observed in cerebral cortex, cerebellum, and brain stem, following the administration of single dose of ammonium acetate. Gangliosides, after extraction from the different brain regions, were estimated by the thiobarbituric acid method and expressed in terms of sialic acid. Individual gangliosides were separated and estimated by thin layer chromatography using resorcinol as the staining agent. These results suggest that ammonia production in the neuronal pathways in brain either as a result of repeated stimulation under physiological conditions or as a result of focal ischemia or injury, may likewise cause an increase in the content of gangliosides which may help in neuritic growth (physiological conditions facilitating synaptic plasticity) and may exert a protective effect on the neurons in the ischemic area against glutamate toxicity.

A(a)LS: Ammonia-induced amyotrophic lateral sclerosis

“…Indeed, although scantly investigated, some investigators reported increased ganglioside levels in ALS including GM2 ganglioside 142 , 173 , 174 . In line with ammonia’s role in ganglioside metabolism, Perez et al showed that ammonia causes leakage of Hexosaminidase A (Hex A), indicating GM2 accumulation 175 , 176 . Thus, ammonia-induced GM2 accumulation could partly explains the heightened vulnerability of motor neurons in ALS ( Figure 2 ).…”

A(a)LS: Ammonia-induced amyotrophic lateral sclerosis

“…Indeed, although scantly investigated, some investigators reported increased ganglioside levels in ALS including GM2 ganglioside [136,166,167]. In line with ammonia's role in ganglioside metabolism, Perez et al showed that ammonia causes leakage of Hexosaminidase A (Hex A), indicating GM2 accumulation [168,169]. Thus, ammonia-induced GM2 accumulation could partly explains the heightened vulnerability of motor neurons in ALS (fig 2).…”