M S Nandhu

Publications (12)21.29 Total impact

• Article: Evaluation of GABA-chitosan nanoparticle induced cell signaling activation during liver regeneration after partial hepatectomy.

  J Shilpa, G Naijil, M S Nandhu, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Liver damage due to infection, cirrhosis, accidents and diseases lead to destruction of hepatocytes and their regeneration to its original form is important for the proper functioning of the body. Gamma aminobutyric acid (GABA), a neurotransmitter, was coupled with a biopolymer chitosan and the nanosized complexes were made. The morphology was studied by scanning electron microscope and the interaction of GABA with chitosan was analysed by FT-IR spectroscopy. The interaction of GABA-chitosan nanoparticles with hepatocytes were observed by FITC labeled nanoparticles. After partial hepatectomy in male Wistar rats, DNA synthesis was estimated by tritiated thymidine uptake and the activity of thymidine kinase and protein synthesis by tritiated leucine uptake in hepatocytes. There was an increase in tritiated thymidine uptake in partially hepatectomised groups with nanoparticle treatment (GCNP) when compared to partially hepatectomised groups without nanoparticle treatment (PHNT) and with pure GABA treatment (G). Inositol 1,4,5 trisphosphate (IP3) content and gene expression of phospholipase C mRNA and nuclear factor kappa-light-chain-enhancer of activated B (NF-KB) mRNA was decreased for groups G and GCNP with respect to PHNT. Thus our results showed increased hepatocyte regeneration with decreased cell death in group G and more better with GCNP when compared to PHNT.
  Journal of Nanoscience and Nanotechnology 08/2012; 12(8):6145-55. · 1.56 Impact Factor
• Article: Glutamate and NMDA receptors activation leads to cerebellar dysfunction and impaired motor coordination in unilateral 6-hydroxydopamine lesioned Parkinson's rat: functional recovery with bone marrow cells, serotonin and GABA.

  M S Nandhu, Jes Paul, Korah P Kuruvila, Pretty M Abraham, Sherin Antony, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterised by a profound and selective loss of nigrostriatal dopaminergic neurons. In Parkinson's disease, degeneration of dopaminergic neurons involves motor structures including basal ganglia and cerebellum. Glutamate-mediated degeneration of the cerebellum contributes to motor dysfunction in Parkinson's disease. Targeting neurotransmitter system beyond the dopamine system is of important, both for the motor and for the nonmotor problems of Parkinson's disease. The aim of this study is to assess the glutamate and NMDA receptor functional regulation and motor performance of 6-hydroxydopamine-induced Parkinson's rat and the effects of serotonin (5-HT), gamma aminobutyric acid (GABA) and bone marrow cells supplementation infused intranigrally to substantia nigra individually and in combination. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in B (max) (P < 0.001) in the cerebellum of 6-hydroxydopamine infused rat compared to control. Real-Time PCR amplification of NMDA2B, mGluR5, and bax were significantly (P < 0.001) upregulated in cerebellum of 6-hydroxydopamine infused rats compared to control. Activation of the glutamate and NMDA receptors gave rise to an increased cAMP and IP3 content in the cerebellum. Gene expression studies of GLAST and CREB showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and motor abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.
  Molecular and Cellular Biochemistry 03/2011; 353(1-2):47-57. · 2.06 Impact Factor
• Source

  Available from: PubMed Central

  Article: Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of unilateral 6-hydroxydopamine induced Parkinson's rats: effect of 5-HT, GABA and bone marrow cell supplementation.

  M S Nandhu, Jes Paul, Korah P Kuruvilla, Anitha Malat, Chinthu Romeo, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.
  Journal of Biomedical Science 01/2011; 18:5. · 2.01 Impact Factor
• Source

  Available from: Smijin S

  Article: Opioid system functional regulation in neurological disease management.

  M S Nandhu, George Naijil, Soman Smijin, S Jayanarayanan, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: There is increasing evidence to suggest a role for the opioid system in the control of pathophysiology of neurological disorders (Alzheimer's, Parkinson's, and Huntington's diseases, spinal cord injury, epilepsy, hypoxia, and autism). Resuscitation of the altered expression of the opioid system in various neurological disorders is of therapeutic importance. Such treatment may be beneficial in ameliorating the clinical symptoms of the disorder. This Mini-Review provides a brief update on opioid system regulation in neurological disorders and focuses on the opioids' pharmacological importance.
  Journal of Neuroscience Research 11/2010; 88(15):3215-21. · 2.74 Impact Factor
• Article: Dopamine D₁ and D₂ receptor subtypes functional regulation in corpus striatum of unilateral rotenone lesioned Parkinson's rat model: effect of serotonin, dopamine and norepinephrine.

  Jes Paul, M S Nandhu, Korah P Kuruvilla, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Parkinson's disease (PD) is due to widespread degeneration in the central and peripheral nervous systems. The hallmark pathology remains in the dopaminergic striatal insufficiency and degeneration of dopaminergic neurons in the substantia nigra. The present study analysed the effect of serotonin (5-HT), 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 corpus striatum of the experimental rats. Unilateral stereotaxic single-dose infusions of rotenone were administered to the substantia nigra of adult male Wistar rats. Neurotransmitters serotonin (5-HT), dopamine, and norepinephrine treatments were given to rotenone induced hemi-Parkinson's rats. Dopamine receptor and its subtypes (D₁ and D₂) binding assay were carried out. Gene expression studies of dopamine D₁ and D₂ were carried out using real-time PCR. Scatchard analysis of dopamine and dopamine D₂ receptor showed a significant increase (P<0.001) and dopamine D₁ receptor showed a significant decrease (P<0.001) in the B(max) in corpus striatum of the PD rats compared to control. These altered parameters were reversed to near control in the serotonin- and norepinephrine-treated PD rats and no change was observed in dopamine-treated PD rats. Real-time PCR results confirmed the receptor data. Our results showed that serotonin and norepinephrine functionally reversed in dopamine receptors in rotenone-induced hemi-Parkinson's rat. This has clinical significance in the therapeutic management of PD.
  Neurological Research 11/2010; 32(9):918-24. · 1.52 Impact Factor
• Article: Targeting glutamate mediated excitotoxicity in Huntington's disease: neural progenitors and partial glutamate antagonist--memantine.

  M Anitha, M S Nandhu, T R Anju, P Jes, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Huntington's disease (HD) is a fatal progressive neurodegenerative disorder with autosomal dominant inheritance. In humans mutated huntingtin (htt) induces a preferential loss of medium spiny neurons (MSN) of the striatum and causes motor, cognitive and emotional deficits. One of the proposed cellular mechanism underlying medium spiny neurons degeneration is excitotoxic pathways mediated by glutamate receptors. The hypothesis proposed is restoration of medium spiny neurons in Huntington's disease using neural progenitor cell implantation and attenuation of glutamate mediated excitotoxicity using a partial glutamate antagonist - Memantine. Memantine can block the NMDA receptors and will prevent excess calcium influx into the neurons decreases the vulnerability of medium spiny neurons to glutamate mediated excitotoxicity. Neural progenitor cell implantation can enhance endogenous neurogenesis process replacing the degenerated medium spiny neurons in the striatum. This has immense significance in the management of Huntington's disease.
  Medical Hypotheses 10/2010; 76(1):138-40. · 1.39 Impact Factor
• Article: Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

  Jobin Mathew, Jes Paul, M S Nandhu, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  Fitoterapia 09/2010; 81(6):546-51. · 1.85 Impact Factor
• Article: GYKI-52466: a potential therapeutic agent for glutamate-mediated excitotoxic injury in Cerebral Palsy.

  M S Nandhu, Jes Paul, Jobin Mathew, T Peeyush Kumar, C S Paulose
  Medical Hypotheses 11/2009; 74(3):619-20. · 1.39 Impact Factor
• Article: Dopamine D1 and D2 receptor functional down regulation in the cerebellum of hypoxic neonatal rats: neuroprotective role of glucose and oxygen, epinephrine resuscitation.

  Binoy Joseph, M S Nandhu, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Brain damage due to an episode of hypoxia remains a major problem in infants causing deficit in motor and sensory function. Molecular processes regulating the dopamine receptors play a very important role in motor and cognitive functions. Disturbances in the development of the dopaminergic system lead to dyskinesia, dystonia, tics and abnormal eye movements. The present study is to understand the hypoxic damage to the dopamine content and dopamine D(1), dopamine D(2) receptors in cerebellum and the neuroprotective effect of glucose supplementation prior to the current sequence of resuscitation-oxygen and epinephrine supplementation in neonatal rats. Dopamine content in the cerebellum showed a significant decrease in hypoxic neonatal rats when compared to control. Dopamine D(1) and dopamine D(2) receptors showed a decrease in B(max) during hypoxia. The cerebellar dopamine, dopamine D(1) and dopamine D(2) receptors showed significant decrease on supplementation of 100% oxygen alone to hypoxic rats when compared to control rats. Dopamine D(1) and dopamine D(2) receptors mRNA showed significant decrease during epinephrine supplementation prior to resuscitation. These dopaminergic receptor alterations were reversed to near control by glucose supplementation. Thus our results suggest that glucose acts as a neuroprotective agent in dopaminergic receptors function. This has immense clinical significance to correct the resuscitation sequence in neonatal care.
  Pharmacological Research 09/2009; 61(2):136-41. · 4.44 Impact Factor
• Article: Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri.

  Amee Krishnakumar, M S Nandhu, C S Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Emotional disturbances, depressive mood, anxiety, aggressive behavior, and memory impairment are the common psychiatric features associated with temporal lobe epilepsy (TLE). The present study was carried out to investigate the role of Bacopa monnieri extract in hippocampus of pilocarpine-induced temporal lobe epileptic rats through the 5-HT(2C) receptor in relation to depression. Our results showed upregulation of 5-HT(2C) receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Also, there was an increase in 5-HT(2C) gene expression and inositol triphosphate content in epileptic hippocampus. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT(2C) receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats. The forced swim test confirmed the depressive behavior pattern during epilepsy that was nearly completely reversed by B. monnieri treatment.
  Epilepsy & Behavior 09/2009; 16(2):225-30. · 2.34 Impact Factor
• Article: Dopamine D1 and D2 receptor functional down regulation in the cerebellum of hypoxic neonatal rats: Neuroprotective role of glucose and oxygen, epinephrine resuscitation

  Binoy Joseph, M.S. Nandhu, C.S. Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Brain damage due to an episode of hypoxia remains a major problem in infants causing deficit in motor and sensory function. Molecular processes regulating the dopamine receptors play a very important role in motor and cognitive functions. Disturbances in the development of the dopaminergic system lead to dyskinesia, dystonia, tics and abnormal eye movements. The present study is to understand the hypoxic damage to the dopamine content and dopamine D1, dopamine D2 receptors in cerebellum and the neuroprotective effect of glucose supplementation prior to the current sequence of resuscitation—oxygen and epinephrine supplementation in neonatal rats. Dopamine content in the cerebellum showed a significant decrease in hypoxic neonatal rats when compared to control. Dopamine D1 and dopamine D2 receptors showed a decrease in Bmax during hypoxia. The cerebellar dopamine, dopamine D1 and dopamine D2 receptors showed significant decrease on supplementation of 100% oxygen alone to hypoxic rats when compared to control rats. Dopamine D1 and dopamine D2 receptors mRNA showed significant decrease during epinephrine supplementation prior to resuscitation. These dopaminergic receptor alterations were reversed to near control by glucose supplementation. Thus our results suggest that glucose acts as a neuroprotective agent in dopaminergic receptors function. This has immense clinical significance to correct the resuscitation sequence in neonatal care.
  Pharmacological Research.
• Article: Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: Antagonism by Bacopa monnieri

  Amee Krishnakumar, M.S. Nandhu, C.S. Paulose
  [show abstract] [hide abstract]
  ABSTRACT: Emotional disturbances, depressive mood, anxiety, aggressive behavior, and memory impairment are the common psychiatric features associated with temporal lobe epilepsy (TLE). The present study was carried out to investigate the role of Bacopa monnieri extract in hippocampus of pilocarpine-induced temporal lobe epileptic rats through the 5-HT2C receptor in relation to depression. Our results showed upregulation of 5-HT2C receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Also, there was an increase in 5-HT2C gene expression and inositol triphosphate content in epileptic hippocampus. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT2C receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats. The forced swim test confirmed the depressive behavior pattern during epilepsy that was nearly completely reversed by B. monnieri treatment.
  Epilepsy & Behavior.