Increased cortical neuronal survival during liver injury: effect of gamma aminobutyric acid and 5-HT chitosan nanoparticles.

Use of nanoparticulate drug delivery system for an effective therapeutic outcome against diseases gains immense hope in the study of drug delivery to partially hepatectomised rats. In the present study, partially hepatectomised rats treated with Gamma aminobutyric acid (GABA) and serotonin (5-HT) chitosan nanoparticles, individually and in combination, were evaluated to analyse their role in GABAB, and 5-HT2A receptors functional regulation, interrelated neuronal survival mechanisms by nuclear factor kappa B (NF-kappaB), tumour necrosis factor-a (TNF-alpha), Akt-1 and the antioxidant enzyme superoxide dismutase (SOD) in the cerebral cortex. A significant decrease in GABA, and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the cerebral cortex to trigger the sympathetic innervations during elevated DNA synthesis in the liver. GABAB, and 5-HT2A signalling directly influenced the cyclic AMP response element binding protein (CREB) expression, neuronal survival and ROS mediated cell damage which was confirmed from the gene expression of NF-kappaB, TNF-alpha, Akt-1 and SOD. In addition to enhanced hepatocyte proliferation, GABA and 5-HT chitosan nanoparticle treatment protected the neurons from ROS mediated cell damage and promoted their survival in the cerebral cortex. This has application in liver based diseases and treatments with nanosized active compounds.

Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.

Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p < 0.001) in dopamine D1 receptor number in the hypoglycaemic condition, suggesting cognitive dysfunction. cAMP content was significantly (p < 0.001) downregulated in hypoglycaemic neonatal rats indicating the reduction in cell signalling of the dopamine D1 receptors. It is attributed to the deficits in spatial learning and memory. Hypoglycaemic neonatal rats treated with Bacopa extract alone and Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

Disruption of cerebellar cholinergic system in hypoxic neonatal rats and its regulation with glucose, oxygen and epinephrine resuscitations.

Cholinergic system is important for respiratory control from the first days of life. Disturbances in cholinergic pathway due to early life stress like hypoxic shock can adversely affect the ventilatory response. The present study evaluates neonatal hypoxic insult mediated cholinergic disturbances and the 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 cerebellum were analyzed. Hypoxic stress decreased cerebellar muscarinic receptor density with a decreased muscarinic M1, M2 and M3 receptor gene expression. The metabolic shift in the acetylcholine synthesis and release is indicated by the decreased cholineacetyl transferase mRNA expression and increased acetylcholine esterase gene expression. Glucose, acting as a precursor for acetyl choline synthesis and an immediate energy source, helps in reversing the cholinergic disturbances in hypoxic neonates. The limitation of immediate oxygenation and epinephrine administration in ameliorating cholinergic disturbances in hypoxic neonates was also reported. This will help in devising a better resuscitation program for the management of neonatal hypoxia.

Accumulation of intracellular polyhydroxybutyrate in Alcaligenes sp. d(2) under phenol stress.

Alcaligenes sp. d(2) isolated from soil was earlier reported as a potent phenol-degrading organism. In the Fourier transform/infrared spectroscopic analysis of the biodegraded sample, the aromatic stretching was missing and the spectrum gave evidence for the presence of polyhydroxybutyric acid along with its depolymerized products. In the gas chromatogram of the biodegraded sample, the peak of phenol at 14.997 min was absent and there were many peaks after 20 min. The organism could carry out 100% degradation of phenol in 32 h and could progressively result in early accumulation of polyhydroxybutyrate (PHB) intracellularly from 8 h onwards. The various conditions optimized for the maximum accumulation of intracellular PHB were pH 7.0, incubation time 24 h, phenol concentration 15 mg/100 ml, and ammonium sulfate concentration 25 mg/100 ml.