ABSTRACT
The development of nanoparticles containing active molecules having improved stability, sustained release and maximum half life helps in cell proliferation result in enhanced tissue regeneration. Our study focuses on the use of Gamma amino butyric acid (GABA) and serotonin (5-HT) coupled chitosan nanoparticles for the active liver regeneration in male Wistar rats. The nanoparticles were prepared and the morphology was studied using SEM. The FT-IR spectra of the nanoparticles and the maximum encapsulation efficiency of GABA and 5-HT binding to chitosan nanoparticles were observed. The in vitro release studies provided the percentage release of GABA and 5-HT from the nanoparticles at different time intervals. The quantification of DNA and protein syntheses was done using [(3)H] thymidine and [(3)H] leucine uptake studies that determined the enhancement in hepatocyte proliferation. Our results project the role of GABA and 5-HT chitosan nanoparticles in the treatment of liver based diseases.
Subject(s)
Chitosan/chemistry , Hepatocytes/cytology , Nanoparticles/chemistry , Serotonin/chemistry , gamma-Aminobutyric Acid/chemistry , Animals , Cell Culture Techniques , Cell Proliferation , Leucine/chemistry , Male , Materials Testing , Microscopy, Electron, Scanning/methods , Neurotransmitter Agents/chemistry , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared/methods , Thymidine/chemistryABSTRACT
Neurotransmitter receptor functional regulation plays an important role in controlling the excitability and responsiveness of hippocampal neurons. Deregulation of its function is associated with seizure generation, motor deficits, and memory impairment. In the present study we investigated the changes in hippocampal cholinergic and GABA receptor binding and gene expression in insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. Expression of cholinergic enzymes; acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) upregulated and downregulated, respectively, in diabetic group, which was further exacerbated by hypoglycemia. Total muscarinic receptor, muscarinic M1, and GABA maximal binding (B(max)) significantly decreased in hypoglycemic and diabetic rats. In hypoglycemic group, the B(max) showed further decline compared with diabetes. Muscarinic M3 receptor B(max) and gene expression upregulated in hypoglycemic and diabetic group. Alpha7 nicotinic acetylcholine receptor (α7 nAChR) expression significantly downregulated in hypoglycemic and diabetic rats. Gene expression of glutamate decarboxylase (GAD), GABAAα1, and GABAB in hypoglycemic and diabetic rats downregulated, with more significant decrease in hypoglycemic group. Present findings show altered cholinergic, muscarinic, nicotinic receptor expression and thereby function. Decreased GABA receptor expression is associated with decline in GABAergic neurotransmission. Thus cholinergic receptor dysfunction and decreased GABAergic neuroprotective inhibitory function in the hippocampus of hypoglycemic and diabetic rats account for the increased vulnerability of hippocampus predisposing to neuronal damage, which is suggested to contribute to cognitive impairment and memory deficit reported in hypoglycemia and diabetes. Also, recurrent hypoglycemia in diabetes exacerbates the hippocampal dysfunction induced by diabetes, which has clinical significance in diabetes therapy.
