A limited range of vagus nerve stimulation intensities produce motor cortex reorganization when delivered during training.

Pairing vagus nerve stimulation (VNS) with rehabilitation has emerged as a potential strategy to improve recovery after neurological injury, an effect ascribed to VNS-dependent enhancement of synaptic plasticity. Previous studies demonstrate that pairing VNS with forelimb training increases forelimb movement representations in motor cortex. However, it is not known whether VNS-dependent enhancement of plasticity is restricted to forelimb training or whether VNS paired with other movements could induce plasticity of other motor representations. We tested the hypothesis that VNS paired with orofacial movements associated with chewing during an unskilled task would drive a specific increase in jaw representation in motor cortex compared to equivalent behavioral experience without VNS. Rats performed a behavioral task in which VNS at a specified intensity between 0 and 1.2 mA was paired with chewing 200 times per day for five days. Intracortical microstimulation (ICMS) was then used to document movement representations in motor cortex. VNS paired with chewing at 0.8 mA significantly increased motor cortex jaw representation compared to equivalent behavioral training without stimulation (Bonferroni-corrected unpaired t-test, p < 0.01). Higher and lower intensities failed to alter cortical plasticity. No changes in other movement representations or total motor cortex area were observed between groups. These results demonstrate that 0.8 mA VNS paired with training drives robust plasticity specific to the paired movement, is not restricted to forelimb representations, and occurs with training on an unskilled task. This suggests that moderate intensity VNS may be a useful adjuvant to enhance plasticity and support benefits of rehabilitative therapies targeting functions beyond upper limb movement.

Reproduction and metamorphosis in the Myristica Swamp tree frog, Mercurana myristicapalustris (Anura: Rhacophoridae).

The reproductive biology of the Myristica Swamp tree frog (Mercurana myristicapalustris), a monotypic rhacophorid frog endemic to the foothills of the Western Ghats mountains of India, has remained unknown since the description of the genus and species. We monitored individuals from parental generation amplexus to the completion of offspring generation tadpole metamorphosis. Surprisingly, our observations revealed that this species exhibits many previously unknown characteristics, including the first ever record of the female, and a diverse call repertoire, consisting of five different call types (the functions of which remain incompletely known). We were also able to determine that reproductive activity peaked during the late pre-monsoon season, that males engaged in intraspecific aggressive encounters to occupy and to defend desirable territories, and that oviposition took place in terrestrial nests made by females. Embryonic development in the unattended nest was followed by tadpole development, which concluded within 40 days. The specific breeding mode employed by Mercurana, which restricts its range to the endangered Myristica swamp ecosystem, likely renders it susceptible to multiple threats, which should be considered jointly in future conservation planning.

A novel third species of the Western Ghats endemic genus Ghatixalus (Anura: Rhacophoridae), with description of its tadpole.

The Western Ghats biodiversity hotspot is a recognized center of rhacophorid diversity as demonstrated by several recent studies. The endemic genus Ghatixalus is represented by two species from two separate high-elevation regions within the Ghats. Here, we describe a third species that can be distinguished by morphological and larval characters, as well as by its phylogenetic placement.

Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide A.

In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of TOPRO stained neurons. Enhanced performance of epileptic rats treated with WS and WA was observed in Radial arm maze test. The antioxidant activity of WS and WA was studied using superoxide dismutase (SOD) and Catalase (CAT) assays in the hippocampus of experimental rats. The SOD activity and CAT activity decreased significantly in epileptic group, treatment with WS and WA significantly reversed the enzymatic activities to near control. Real time gene expression studies of SOD and GPx showed significant up-regulation in epileptic group compared to control. Treatment with WS and WA showed significant reversal to near control. Lipid peroxidation quantified using TBARS assay, significantly increased in epileptic rats. Treatment with WS and WA showed significant reversal to near control. NMDA receptor expression decreased in epileptic rats. The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.

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

BACKGROUND: 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. METHODS: In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. RESULTS: Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit 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. CONCLUSIONS: Bacopa monnieri 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; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

Dopamine D1 and D2 receptor subtypes functional regulation in cerebral cortex of unilateral rotenone lesioned Parkinson's rat model: Effect of serotonin, dopamine and norepinephrine.

Parkinson's disease is a progressive neurodegenerative disorder characterized by selective degeneration of dopaminergic neurons in substantia nigra pars compacta leading to marked reduction of dopamine levels in the cerebral cortex. The present study analysed the effect of serotonin, dopamine and norepinephrine as treatment on rotenone induced Hemi-Parkinson's disease in rats and its role in the regulation of dopamine receptor subtypes in the cerebral cortex of the experimental rats. Unilateral stereotaxic single dose infusions of rotenone were administered to the substantia nigra of adult male Wistar rats. Neurotransmitters--serotonin, dopamine and norepinephrine treatments--were given to rotenone induced Hemi-Parkinson's rats. Scatchard analysis of Dopamine D1 and D2 receptor showed a significant increase (p < 0.001) in the cerebral cortex of the Parkinson's rats compared to control. These altered parameters were reversed to near control in the serotonin and norepinephrine treated Parkinson's disease rats and no change was observed in dopamine treated Parkinson's rats. Real-time PCR results confirmed the receptor data. Our results showed serotonin and norepinephrine functionally reversed the dopamine receptors significantly in rotenone induced Hemi-Parkinson's rat. This has clinical significance in the therapeutic management of Parkinson's disease.

Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά1), GABA(Aά5) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

The healing power of well-being.

Neuroendocrine system plays an important role in modulating our body functions and emotions. At the same time, emotions implicate a pivotal role in the regulation of brain function and neuroendocrine system. Negative affective states such as depression and stress are associated with premature mortality and increase the risk of various fatal diseases. It has been suggested that positive affective states are protective and improve our health and productiveness. Several potential mechanisms have been posited to account for these associations including improved health behaviour, direct physiological benefits, enhanced resistance and recovery from stress among individuals with high versus low positive emotional resources. This review summarises information concerning the neuronal and hormonal systems in mood, impact of negative and positive affective states on the level of cortisol, epinephrine, serotonin, dopamine and endorphins. The functional correlation of neuronal and hormonal systems in the development of diseases and their ability to enhance health-relevant biological processes are also evaluated.

Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.

Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT(2A) receptor subtype, gene expression studies on 5-HT(2A), 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters B(max) and Kd showed a significant decrease (p < 0.001) whereas 5-HT(2A) receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT(2A), 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, B(max), Kd of 5-HT, 5-HT(2A) and gene expression of 5-HT(2A), 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.

Cerebellar 5HT2A receptor function under hypoxia in neonatal rats: role of glucose, oxygen, and epinephrine resuscitation.

Molecular processes regulating the cerebellar serotonergic receptors play an important role in the control of respiration and cognitive functions under hypoxia. The present study examined cerebellar 5HT receptor alterations and neuroprotective effect of glucose supplementation prior to current sequence of resuscitation-oxygen and epinephrine supplementation in hypoxic neonatal rats. Hypoxic stress increased the number of total 5HT and 5HT(2A) receptors along with an up-regulation of 5HT transporter and 5HT(2A) receptor gene in cerebellum. These serotonergic alterations were reversed to near control by glucose supplementation. Immunohistochemical studies confirmed the data. Behavioral studies revealed the cognitive impairment due to neonatal hypoxia in the later stages of life and the role of timely glucose supplementation in preventing these behavioral deficits. The enhanced cerebellar 5HT(2A) receptors may act as a modulator of ventilatory response to hypoxia, which can in turn result in cognitive dysfunction. Glucose supplementation helped in managing the serotonergic functional alterations. This has immense clinical significance in neonatal care.

Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: effect of Bacopa monnieri and bacoside-A.

AIM OF THE STUDY: Gamma-aminobutyric acid A receptors are the principal mediators of synaptic inhibition in striatal neurons and play an important role in preventing the spreading of seizures through the striatum. In the present study, effect of Bacopa monnieri (L.) Pennel and its active component bacoside-A on spatial recognition memory deficit and alterations of GABA receptor in the striatum of epileptic rats were investigated. MATERIALS AND METHODS: Total GABA and GABA(A) receptor numbers in the control and epileptic rats were evaluated using [(3)H]GABA and [(3)H]bicuculline binding. GABA(Aalpha1,) GABA(Aalpha5,) GABA(Agamma3) and GABA(Adelta) gene expressions were studied. Behavioral performance was assed using Y-maze. RESULTS: Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the striatum of epileptic rats showed significant decrease in B(max) compared to control. Real-Time PCR amplification of GABA(A) receptor subunits such as GABA(Aalpha1,) GABA(Aalpha5) and GABA(Adelta), were down regulated (p<0.001) in the striatum of epileptic rats compared to control. Epileptic rats have deficit in Y-maze performance. Bacopa monnieri and bacoside-A treatment reversed these changes to near control. CONCLUSION: Our results suggest that decreased GABA receptors in the striatum have an important role in epilepsy associated motor learning deficits and Bacopa monnieri and bacoside-A has a beneficial effect in the management of epilepsy.

Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.

In the present study, the effects of Bacopa monnieri and its active component, bacoside A, on motor deficit and alterations of GABA receptor functional regulation in the cerebellum of epileptic rats were investigated. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats revealed a significant decrease in B(max) compared with control. Real-time polymerase chain reaction amplification of GABA(A) receptor subunits-GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (P<0.001) in the cerebellum of epileptic rats compared with control rats. Epileptic rats exhibit deficits in radial arm and Y-maze performance. Treatment with B. monnieri and bacoside A reversed these changes to near-control levels. Our results suggest that changes in GABAergic activity, motor learning, and memory deficit are induced by the occurrence of repetitive seizures. Treatment with B. monnieri and bacoside A prevents the occurrence of seizures thereby reducing the impairment of GABAergic activity, motor learning, and memory deficit.

Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.

Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats.

Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH and C + IIH). alpha7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and alpha7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar dysfunction associated with hypoglycemia.

Bacopa monnieri and Bacoside-A for ameliorating epilepsy associated behavioral deficits.

Bacopa monnieri is an outstanding nervine tonic used for raising the mental performance. It helps in concentration, comprehension, recall and alertness, Brahmi is particularly beneficial as it aids in categorizing information in brain and its subsequent expression. Bacopa is also called as a natural antioxidant which may give details its neuroprotective role seen in the memory centers of the brain. Epilepsy is neuronal disorder characterized by learning, cognitive and memory impairments. The present review summarizes information concerning botany, chemistry and beneficial effect of Bacopa monnieri on epilepsy associated behavioral deficits.

Cholinergic and glutamergic receptor functional regulation in long-term, low dose somatotropin and insulin treatment to ageing rats: rejuvenation of brain function.

The role of somatotropin and insulin treatment in the regulation of neurotransmitter levels in the ageing brain is not fully established. We evaluated the long-term, low dose effects of somatotropin and insulin on acetylcholine and glutamate receptor subtypes functional regulation in the cerebral cortex of young (4-16 weeks) and old rats (60-90 weeks). Somatotropin and insulin treated young rats showed significant upregulation in muscarinic M1 and M3 expression whereas in old rats, somatotropin and insulin treatment downregulated M1 and M3 expression. N-methyl-D-aspartate and metabotropic glutamate receptor gene expression were significantly downregulated with somatotropin treatment while insulin treatment showed upregulation in both young and old rats. Acetylcholine esterase activity showed a decrease with age and after somatotropin and insulin treatment, the activity increased in both young and old rats. Electroencephalogram studies confirmed the brain wave activity in both young and old somatotropin and insulin treated rats. The results highlight long-term low dose somatotropin and insulin treatment in regulating cholinergic and glutamergic receptors subtypes in ageing rats and rejuvenation of brain function.

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats.

Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR) have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). Previous reports from our laboratory on streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ--diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax) and affinity (Kd) of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

Muscarinic M(1), M(3) receptors function in the brainstem of streptozotocin induced diabetic rats: their role in insulin secretion from the pancreatic islets as a function of age.

In the present study, we have investigated acetylcholine esterase (AChE) activity and muscarinic M(1), M(3) receptors kinetics in the brainstem of both young and old streptozotocin induced and insulin treated diabetic rats (D + I). Also, the functional role of acetylcholine and muscarinic receptors in insulin secretion from the pancreatic islets was studied in vitro. 90 week old control rats showed decreased V(max) (P < 0.001) for AChE compared to 7 week old control rats. V(max) was decreased (P < 0.001) in 7 week diabetic groups whereas 90 week old diabetic groups showed increased (P < 0.001) V(max) when compared to their respective controls. Binding studies using [(3)H]QNB and [(3)H]DAMP of 90 week old control showed significant increase in the B(max) (P < 0.001) and K(d) (P < 0.01) of muscarinic M(1) receptors whereas M(3) receptor number was decreased significantly (P < 0.001) with no change in affinity when compared to 7 week old control respectively. M(1) receptor number was decreased significantly (P < 0.001) whereas M(3) receptor number was increased significantly (P < 0.001) in both 7 week and 90 week old diabetic rat groups compared to their respective controls. The competition curve for [(3)H]QNB fitted for two sited model in 7 week old groups whereas fitted for one sited model in 90 week old groups. [(3)H]DAMP was fitted for two sited model in both 7 week and 90 week old groups. Insulin treatment significantly reversed (P < 0.001) the binding parameters to near control level. In vitro studies showed that acetylcholine through muscarinic M(1) and M(3) receptors stimulated insulin secretion from the pancreatic islets. Thus our studies suggest that both brainstem and pancreatic muscarinic M(1), M(3) receptors differentially regulate the cholinergic activity and insulin secretion which will have clinical significance in the management of diabetes and insulin treatment as a function of age.