Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

<p>Abstact</p> <p>Background</p> <p>Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue.</p> <p>Methods</p> <p>In the present study, alterations of the general GABA, GABA_Aand GABA_Breceptors in the cerebral cortex of the epileptic rat and the therapeutic application of <it>Bacopa monnieri </it>were investigated.</p> <p>Results</p> <p>Scatchard analysis of [³H]GABA, [³H]bicuculline and [³H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in B_max(P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABA_Aά1, GABA_Aγ, GABA_Aδ, GABA_Band GAD where down regulated (P < 0.001) in epileptic rats. GABA_Aά5subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance.</p> <p>Conclusions</p> <p><it>Bacopa monnieri </it>and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; <it>Bacopa monnieri </it>and Bacoside-A have therapeutic application in epilepsy management.</p

Muscarinic M1 and M3 Receptors,IP3 and cGMP Functional Regulation in Streptozotocin Induced Diabetic Rats: Insulin and Somatotropin Induced Rejuvenation as a Function of Age

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.Department of Biotechnology, Cochin University of Science and Technolog

Glutamate (mGluR-5) gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets <it>in vitro</it>

Abstract Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function.</p

A study of donor area in follicular unit hair transplantation

Background: The advent of follicular unit transplantation (FUT) has given a natural appearance in the recipient area in the past two decades, but has left behind an unsightly scar in the donor area. A study of donor area and techniques to make it cosmetically acceptable is lacking. Aim: The aim of this study was to evaluate the donor area after follicular unit hair transplantation and to show a few techniques to make the donor scar aesthetically pleasing. Materials and Methods: The donor area was examined for scar width and patient satisfaction scores of donor area in 30 consecutive patients from March 2012 to February 2013 retrospectively after a minimum of 3 months after the procedure. Complications such as effluvium along suture line, wound infection, dehiscence, necrosis, folliculitis, keloids and wide scars were also noted. Results: Scar width increased with increase in width of the donor strip. Patient satisfaction scores declined with larger strip widths. The most common complication seen was folliculitis-like lesions. Double trichophytic closure yielded the most aesthetically acceptable scar. Conclusion: FUT produces a linear scar in the donor area, which can be a significant concern in patients wishing to cut their hair short. Restricting the width of the donor strip and trichophytic closure has greatly improved the appearance of the scar

Railroading technique of dermal grafting for linear atrophic scarring

Dermal grafting is a valuable technique in the field of dermatosurgery for the treatment of atrophic scars where the source of filler material is the patient′s own dermis. However, it is underused for the reasons being difficulties in placing the graft in the tunnel, keratin cysts and complications due to biofilms. Railroading technique used in urology for rupture urethra has been described for dermal grafts to overcome the technical difficulties of graft placement

Glutamate (mGluR-5) gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

Metabotrophic glutamate receptors (mGluRs) modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5) in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I) as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10(-7 )M) stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function