Design Of Metal Architectures: Synthesis And Study Of Their Photophysical And Biomolecular Recognition Properties

Design and study of molecular receptors capable of mimicking natural processes has found applications in basic research as well as in the development of potentially useful technologies. Of the various receptors reported, the cyclophanes are known to encapsulate guest molecules in their cavity utilizing various non–covalent interactions resulting in significant changes in their optical properties. This unique property of the cyclophanes has been widely exploited for the development of selective and sensitive probes for a variety of guest molecules including complex biomolecules. Further, the incorporation of metal centres into these systems added new possibilities for designing receptors such as the metallocyclophanes and transition metal complexes, which can target a large variety of Lewis basic functional groups that act as selective synthetic receptors. The ligands that form complexes with the metal ions, and are capable of further binding to Lewis-basic substrates through open coordination sites present in various biomolecules are particularly important as biomolecular receptors. In this context, we synthesized a few anthracene and acridine based metal complexes and novel metallocyclophanes and have investigated their photophysical and biomolecular recognition properties.

Decreased GABAA Receptors Functional Regulation 3 in the Cerebral Cortex and Brainstem of Hypoxic Neonatal Rats: 4 Effect of Glucose and Oxygen Supplementation

Hypoxia in neonates can lead to biochemical and molecular alterations mediated through changes in neurotransmitters resulting in permanent damage to brain. In this study, we evaluated the changes in the receptor status of GABAA in the cerebral cortex and brainstem of hypoxic neonatal rats and hypoxic rats supplemented with glucose and oxygen using binding assays and gene expression of GABAAa1 and GABAAc5. In the cerebral cortex and brainstem of hypoxic neonatal rats, a significant decrease in GABAA receptors was observed, which accounts for the respiratory inhibition. Hypoxic rats sup- plemented with glucose alone and with glucose and oxygen showed, respectively, a reversal of the GABAA receptors, andGABAAa1 and GABAAc5 gene expression to control. Glucose acts as an immediate energy source thereby reducing the ATP-depletion-induced increase in GABA and oxygenation, which helps in encountering anoxia. Resuscitation with oxygen alone was less effective in reversing the receptor alterations. Thus, the results of this study suggest that reduction in the GABAA receptors functional regulation during hypoxia plays an important role in mediating the brain damage. Glucose alone and glucose and oxygen supplementation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.

GABA, serotonin, muscarinic receptors - their second messengers and transcription factors functional regulation in the brain regions of hypoxic neonatal rats: Resuscitation with glucose, oxygen and epinephrine

The present study was designed to investigate the protective effect of glucose, oxygen and epinephrine resuscitation on impairment in the functional role of GABAergic, serotonergic, muscarinic receptors, PLC, BAX, SOD, CAT and GPx expression in the brain regions of hypoxia induced neonatal rats. Also, the role of hormones - Triiodothyronine (T3) and insulin, second messengers – cAMP, cGMP and IP3 and transcription factors – HIF and CREB in the regulation of neonatal hypoxia and its resuscitation methods were studied. Behavioural studies were conducted to evaluate the motor function and cognitive deficit in one month old control and experimental rats. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The sequence of glucose, epinephrine and oxygen administration at the molecular level is an important aspect of the study. The additive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures by initial supply of glucose to hypoxic neonatal rats showed from the molecular study when brought to practice will lead to healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

Bone marrow cells differentiation to neurons in the rat brain using Serotonin and GABA:Their role on glutamate receptors, IP3, cAMP and cGMP functional regulation in unilateral Parkinsonism induced by 6-hydroxydopamine

Parkinson's disease is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Our findings demonstrated that glutamatergic system is impaired during PD. The evaluations of these damages have important implications in understanding the molecular mechanism underlying motor, cognitive and memory deficits in PD. Our results showed a significant increase of glutamate content in the brain regions of 6- OHDA infused rat compared to control. This increased glutamate content caused an increase in glutamatergic and NMDA receptors function. Glutamate receptor subtypes- NMDAR1, NMDA2B and mGluR5 have differential regulatory role in different brain regions during PD. The second messenger studies confirmed that the changes in the receptor levels alter the IP3, cAMP and cGMP content. The alteration in the second messengers level increased the expression of pro-apoptotic factors - Bax and TNF-α, intercellular protein - α-synuclein and reduced the expression of transcription factor - CREB. These neurofunctional variations are the key contributors to motor and cognitive abnormalities associated with PD. Nestin and GFAP expression study confirmed that 5-HT and GABA induced the differentiation and proliferation of the BMC to neurons and glial cells in the SNpc of rats. We also observed that activated astrocytes are playing a crucial role in the proliferation of transplanted BMC which makes them significant for stem cell-based therapy. Our molecular and behavioural results showed that 5-HT and GABA along with BMC potentiates a restorative effect by reversing the alterations in glutamate receptor binding, gene expression and behaviour abnormality that occur during PD. The therapeutic significance in Parkinson’s disease is of prominence.