Jayanarayanan, S; Dr. Paulose, C S(Cochin University Of Science And Technology, December 21, 2012)
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Abstract:
The present study was designed to investigate the protective effect of
curcumin and vitamin D3 in the functional regulation of glutamatergic NMDA and
AMPA receptors in streptozotocin (STZ) induced diabetic rats. Alterations in
glutamatergic neurotransmission in the brain were evaluated by analyzing the
glutamate content, glutamate receptors - NMDA and AMPA receptors binding
parameters and gene expression, GAD and GLAST gene expression.
Immunohistochemistry studies using confocal microscope were carried out to
confirm receptor density and gene expression results of NMDA and AMPA
receptors. The role of glutamatergic receptors in pancreas was studied using the
following parameters; glutamate content, GLAST expression, glutamate receptors
- NMDA and AMPA receptor binding and gene expression. Increasing evidence in
both experimental and clinical studies suggests that oxidative stress plays a major
role in the pathogenesis of diabetes. In the present study SOD assay and GPx gene
expression were done to evaluate the activity of antioxidant enzymes in the brain
regions and pancreas. NeuroD1 and Pdx1 gene expression were performed in
pancreas of experimental rats to evaluate pancreatic islet survival. Gene
expression profiles of caspase 8, Bax, and Akt in brain regions and pancreas were
studied to understand the possible mechanism behind curcumin and vitamin D3
mediated neuroprotection and islet survival. Gene expression studies of
vitamin D3 receptor localisation in the pancreas was done to understand the
mechanism of vitamin D3 in insulin secretion. Curcumin and vitamin D3 mediated
insulin secretion via Ca2+ release were studied using confocal microscope.
Description:
Department of Biotechnology
Cochin University of Science and Technology
Savitha, Balakrishnan; Dr. Paulose, C S(Cochin University of Science and Technology, January , 2008)
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Abstract:
The present study describes that acetylcholine through muscarinic Ml and
M3 receptors play an important role in the brain function during diabetes as a function
of age. Cholinergic activity as indicated by acetylcholine esterase, a marker for
cholinergic function, decreased in the brain regions - the cerebral cortex, brainstem
and corpus striatum of old rats compared to young rats. in diabetic condition, it was
increased in both young and old rats in cerebral cortex, and corpus striatum while in
brainstem it was decreased. The functional changes in the muscarinic receptors were
studied in the brain regions and it showed that muscarinic M I receptors of old rats
were down regulated in cerebral cortex while in corpus striatum and brainstem it was
up regulated. Muscarinic M3 receptors of old rats showed no significant change in
cerebral cortex while in corpus striatum and brainstem muscarinic receptors were
down regulated. During diabetes, muscarinic M I receptors were down regulated in
cerebral cortex and brainstem of young rats while in corpus striatum they were up
regulated. In old rats, M I receptors were up regulated in cerebral cortex, corpus
striatum and in brainstem they were down regulated. Muscarinic M3 receptors were
up regulated in cerebral cortex and brainstem of young rats while in corpus striatum
they were down regulated. In old rats, muscarinic M l receptors were up regulated in
cerebral cortex, corpus striatum and brainstem. In insulin treated diabetic rats the
activity of the receptors were reversed to near control. Pancreatic muscarinic M3
receptor activity increased in the pancreas of both young and old rats during diabetes.
In vitro studies using carbachol and antagonists for muscarinic Ml and M3 receptor
subtypes confirmed the specific receptor mediated neurotransmitter changes during
diabetes. Calcium imaging studies revealed muscarinic M I mediated Ca2
+ release
from the pancreatic islet cells of young and old rats. Electrophysiological studies
using EEG recording in young and old rats showed a brain activity difference during diabetes. Long term low dose STH and INS treated rat brain tissues were used for
gene expression of muscarinic Ml, M3, glutamate NMDARl, mGlu-5,alpha2A, beta2,
GABAAa1 and GABAB, DAD2 and 5-HT 2C receptors to observe the neurotransmitter
receptor functional interrelationship for integrating memory, cognition and
rejuvenating brain functions in young and old. Studies on neurotransmitter receptor
interaction pathways and gene expression regulation by second messengers like IP3
and cGMP in turn will lead to the development of therapeutic agents to manage
diabetes and brain activity.From this study it is suggested that functional improvement of
muscarinic Ml, M3, glutamate NMDAR1, mGlu-5, alpha2A, beta2, GABAAa1 and GABAB,
DAD2 and 5-HT 2C receptors mediated through IP3 and cGMP will lead to therapeutic
applications in the management of diabetes. Also, our results from long term low dose
STH and INS treatment showed rejuvenation of the brain function which has clinical
significance in maintaining healthy period of life as a function of age.
Description:
Department of Biotechnology,
Cochin University of Science and Technology
Sherin, Antony; Dr. Paulose, C S(Cochin University of Science & Technology, May , 2010)
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Abstract:
In the present study, a detailed investigation on the alterations of
muscarinic M1, M3, α7 nicotinic acetylcholine receptor (α7 nAchR), GABA
receptors and its subtypes; GABAAα1 and GABAB in the brain regions of
streptozotocin induced diabetic and insulin induced hypoglycemic rats were
carried out. Gene expression of acetylcholine esterase (AChE), choline
acetyltransferase (ChAT), GAD, GLUT3, Insulin receptor, superoxide dismutase
(SOD), Bax protein, Phospholipase C and CREB in hypoglycemic and
hyperglycemic rat brain were studied. Muscarinic M1, M3 receptors, AChE,
ChAT, GABAAα1, GABAB, GAD, Insulin receptor, SOD, Bax protein and
Phospholipase C expression in pancreas was also carried out. The molecular
studies on the CNS and PNS damage will elucidate the therapeutic role in the
corrective measures of the damage to the brain during hypoglycemia and
hyperglycemia.
Description:
Department of Biotechnology,Cochin University of Science and Technology