title: Tolerance of hyperammonemia in brain of Heteropneustes fossilis is supported by glutamate-glutamine cycle.
abstract: This report presents analysis of molecular switches associated with tolerance to hyperammonemia in Heteropneustes fossilis because it tolerates about 100-fold more ammonia than mammals. Brains of Heteropneustes fossilis exposed to 100mM ammonium chloride were dissected after Zero hour as control, 16h and 20h exposure. The status of neuron and glia were analysed by Golgi staining, Luxol Fast Blue, and Nissl's staining. The expression patterns of genes associated to homeostasis of neuron and glia, management of oxidative stress and inflammation, ammonia metabolism and brain derived neurotrophic factor were analysed through reverse-transcriptase-polymerase chain reaction. After 20h of hyperammonemia glia were more degenerated than neurons. The expression of mRNA of lactate dehydrogenase (Ldh), super oxide dismutase (Sod), catalase (Catalase), arginase-I (Arg I), inducible nitric oxide (iNos), glutaminase (GA), and brain derived neurotrophic factor (Bdnf) was up-regulated than the control. The levels of mRNA of Arg II, glutamate dehydrogenase (Gdh), glutamine synthetase (GS), glial fibrillary acidic protein (Gfap), proliferating cell nuclear antigen (Pcna) and S100β were down-regulated than control due to hyperammonemia. It appears first observation on impact of hyperammonemia on the status of neurons, myelination and glial cells in brain of Heteropneustes fossilis by Golgi staining, Nissl's and Luxol Fast Blue staining. The distribution of ammonia and glutamate metabolising enzymes in brain supports multi-centric mechanism (s) of regulation. The expression of Arg I and Arg II gets inversely regulated and glutamate-glutamine cycle also operates in Heteropneustes fossilis against hyperammonemia in brain.
authors.affiliation: Biochemistry and Molecular Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Biochemistry and Molecular Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address: rmishraa@bhu.ac.in.
authors.forename: Rajnikant
authors.initials: R
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002397:Catfishes / Q000378:metabolism*; D004660:Encephalitis / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D022124:Hyperammonemia / Q000097:blood* / Q000235:genetics / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D012313:RNA; D001119:Arginase
keywords: Arginase; Glutaminase; Golgi staining; Hyperammonemia; Neuronal degeneration