ABSTRACT
Molecular processes regulating cholinergic functions play an important role in the control of respiration under neonatal hypoxia. The present study evaluates neonatal hypoxic insult-mediated cholinergic alterations and the protective role of glucose, oxygen and epinephrine resuscitation. The changes in total muscarinic, muscarinic M1, M2, M3 receptors and the enzymes involved in acetylcholine metabolism--cholineacetyl transferase and acetylcholine easterase in the brain stem were analyzed. Hypoxic stress decreased total muscarinic receptors along with a reduction in muscarinic M1, M2 and M3 receptor genes in the brain stem. The reduction in acetylcholine metabolism is indicated by the down regulated cholineacetyl transferase and up regulated acetylcholine easterase expression. These cholinergic disturbances in the brain stem were reversed by glucose resuscitation to hypoxic neonates. The adverse effects of immediate oxygenation and epinephrine administration were also reported. This has immense clinical significance in establishing a proper resuscitation for the management of neonatal hypoxia.
Subject(s)
Blood Glucose/metabolism , Brain Stem/metabolism , Choline O-Acetyltransferase/metabolism , Epinephrine/pharmacology , Hypoxia, Brain/pathology , Receptors, Muscarinic/metabolism , Animals , Animals, Newborn , Brain Stem/drug effects , Choline O-Acetyltransferase/genetics , Cholinesterases/genetics , Cholinesterases/metabolism , Coloring Agents , Disease Models, Animal , Gene Expression/drug effects , Glutathione/genetics , Glutathione/metabolism , Muscarinic Antagonists/pharmacokinetics , Protein Binding/drug effects , Quinuclidinyl Benzilate/pharmacokinetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Muscarinic/genetics , Regression Analysis , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Tritium/pharmacokineticsABSTRACT
Liver damage due to infection, cirrhosis, accidents and diseases lead to destruction of hepatocytes and their regeneration to its original form is important for the proper functioning of the body. Gamma aminobutyric acid (GABA), a neurotransmitter, was coupled with a biopolymer chitosan and the nanosized complexes were made. The morphology was studied by scanning electron microscope and the interaction of GABA with chitosan was analysed by FT-IR spectroscopy. The interaction of GABA-chitosan nanoparticles with hepatocytes were observed by FITC labeled nanoparticles. After partial hepatectomy in male Wistar rats, DNA synthesis was estimated by tritiated thymidine uptake and the activity of thymidine kinase and protein synthesis by tritiated leucine uptake in hepatocytes. There was an increase in tritiated thymidine uptake in partially hepatectomised groups with nanoparticle treatment (GCNP) when compared to partially hepatectomised groups without nanoparticle treatment (PHNT) and with pure GABA treatment (G). Inositol 1,4,5 trisphosphate (IP3) content and gene expression of phospholipase C mRNA and nuclear factor kappa-light-chain-enhancer of activated B (NF-KB) mRNA was decreased for groups G and GCNP with respect to PHNT. Thus our results showed increased hepatocyte regeneration with decreased cell death in group G and more better with GCNP when compared to PHNT.
Subject(s)
Chitosan/chemistry , Hepatectomy , Liver Regeneration , Nanoparticles , Signal Transduction , gamma-Aminobutyric Acid/chemistry , Animals , Male , Microscopy, Electron, Scanning , Rats , Rats, Wistar , Spectroscopy, Fourier Transform InfraredABSTRACT
Intensive glycemic control during diabetes is associated with an increased incidence of hypoglycemia, which is the major barrier in blood glucose homeostasis during diabetes therapy. The CNS neurotransmitters play an important role in the regulation of glucose homeostasis. In the present study, we showed the effects of hypoglycemia in diabetic and non- diabetic rats on motor functions and alterations of GABA receptor and CREB expression in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. Scatchard analysis of [(3)H]GABA binding in the cerebellum of diabetic hypoglycemic and control hypoglycemic rats showed significant (P<0.01) decrease in B(max) and K(d) compared to diabetic and control rats. Real-time PCR amplification of GABA receptor subunit GABA(Aα1) and GAD showed significant (P<0.001) down-regulation in the cerebellum of hypoglycemic rats compared to diabetic and control rats. Confocal imaging study confirmed the decreased GABA receptors in hypoglycemic rats. CREB mRNA expression was down-regulated during recurrent hypoglycemia. Both diabetic and non-diabetic hypoglycemic rats showed impaired performance in grid walk test compared to diabetic and control. Impaired GABA receptor and CREB expression along with motor function deficit were more prominent in hypoglycemic rats than hyperglycemic which showed that hypoglycemia is causing more neuronal damage at molecular level. These molecular changes observed during hypo/hyperglycemia contribute to motor and learning deficits which has clinical significance in diabetes treatment.
