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1.
J Neurol Sci ; 331(1-2): 31-7, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23726276

RESUMO

Oxidative stress-induced neuronal cell death has been implicated in Parkinson's disease (PD). Oxidative stress initiated by 6-hydroxydopamine (6-OHDA) causes mitochondrial dysfunction leading to apoptosis and Parkinsonian neurodegeneration. We investigated the neuroprotective potential of serotonin (5-HT), gamma amino butyric acid (GABA) and autologous bone marrow cells (BMC) in combination against oxidative stress-induced cell death. PD was induced in adult male Wistar rats by intranigral infusion of 6-OHDA (8 µg/µl). The activities of antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analysed. The extent of lipid peroxidation was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARs). Real Time PCR gene expression of SOD, CAT and GPx were performed using specific Taqman probes. 6-OHDA induced decreased activity of SOD, CAT and GPx in corpus striatum was significantly reversed to near control (p<0.001) by treatment with 5-HT, GABA and bone marrow cells. Gene expression studies of SOD, CAT and GPx using Real Time PCR confirmed the above observation. TBAR levels were elevated (p<0.001) in 6-OHDA treated rats indicating lipid peroxidation. 5-HT and GABA along with autologous bone marrow cell supplementation significantly ameliorated 6-OHDA-induced lipid peroxidation (p<0.001). Our results suggest a new therapeutic strategy of neuroprotection against damage by oxidative stress in Parkinson's disease.


Assuntos
Adrenérgicos/toxicidade , Transplante de Medula Óssea/métodos , Corpo Estriado , Oxidopamina/toxicidade , Doença de Parkinson , Serotonina/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Análise de Variância , Animais , Catalase/genética , Catalase/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
2.
Mol Cell Biochem ; 353(1-2): 47-57, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21384157

RESUMO

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.


Assuntos
Doenças Cerebelares/fisiopatologia , Atividade Motora/fisiologia , Doença de Parkinson Secundária/fisiopatologia , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Ligação Competitiva , Doenças Cerebelares/induzido quimicamente , Doenças Cerebelares/terapia , Cerebelo/metabolismo , Cerebelo/fisiopatologia , AMP Cíclico/metabolismo , Maleato de Dizocilpina/metabolismo , Fosfatos de Inositol/metabolismo , Masculino , Microscopia Confocal , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/terapia , Ratos , Ratos Wistar , Receptor de Glutamato Metabotrópico 5 , Receptores de Glutamato/genética , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
3.
J Biomed Sci ; 18: 5, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21235809

RESUMO

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.


Assuntos
Transplante de Medula Óssea , Córtex Cerebral/metabolismo , AMP Cíclico/metabolismo , Ácido Glutâmico/metabolismo , Fosfatos de Inositol/metabolismo , Oxidopamina/efeitos adversos , Doença de Parkinson Secundária/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Masculino , Oxidopamina/farmacologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologia , Doença de Parkinson Secundária/terapia , Ratos , Ratos Wistar , Substância Negra/metabolismo , Substância Negra/patologia , Transplante Homólogo
4.
Fitoterapia ; 81(6): 546-51, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20117182

RESUMO

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.


Assuntos
Anticonvulsivantes/uso terapêutico , Bacopa , Epilepsia/tratamento farmacológico , Fitoterapia , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Carbamazepina/uso terapêutico , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Epinefrina/sangue , Insulina/sangue , Malato Desidrogenase/metabolismo , Masculino , Agonistas Muscarínicos , Miocárdio/enzimologia , Norepinefrina/sangue , Pilocarpina , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Tri-Iodotironina/sangue
5.
J Mol Neurosci ; 41(1): 1-11, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19578995

RESUMO

Parkinson's disease is the second most common neurodegenerative disorder and remains incurable. Many potential compensatory mechanisms have now been proposed; these are both dopaminergic, focused on enhancing effects or exposure to existing dopamine, and non-dopaminergic, being focused on reducing activity of the indirect striatal output pathway. In the present study, the effects of serotonin, gamma-aminobutyric acid, and bone marrow cell supplementation intranigrally to the substantia nigra on unilateral 6-hydroxydopamine-infused rats were analyzed individually. Dopaminergic binding parameters were done by Scatchard analysis of dopamine D(1) receptor-binding assay using [(3)H]SCH 23390. In the corpus striatum, 6-hydroxydopamine-infused rats showed a significant decrease in B (max) (P < 0.001), and in cerebral cortex, they showed a significant increase in B (max) (P < 0.001) compared to control. Real-time polymerase chain reaction amplification of dopamine D(1) was downregulated (P < 0.001) in the corpus striatum of 6-hydroxydopamine-infused rats compared to control, whereas in the cerebral cortex, it showed a significant upregulation (P < 0.001). Behavioral studies were carried out to confirm the biochemical and molecular studies. Serotonin and gamma-aminobutyric acid supplementation reversed these changes to control. The bone marrow cell-treated group of our studies does not show much significant change as compared to the serotonin and gamma-aminobutyric acid-supplemented groups. The alterations in dopamine D(1) receptor-binding parameters and gene expression during Parkinson's model were reversed by serotonin and gamma-aminobutyric acid supplementation in our experiments, which has clinical significance in the management of the disease.


Assuntos
Adrenérgicos/toxicidade , Transplante de Medula Óssea , Oxidopamina/toxicidade , Transtornos Parkinsonianos , Receptores de Dopamina D1 , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Dopamina/metabolismo , Masculino , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/terapia , Ensaio Radioligante , Ratos , Ratos Wistar , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo
6.
Fitoterapia ; 81(5): 315-22, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19944749

RESUMO

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.


Assuntos
Antioxidantes/uso terapêutico , Bacopa/química , Cognição/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Antioxidantes/farmacologia , Epilepsia/psicologia , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Triterpenos/farmacologia
7.
Epilepsy Behav ; 16(2): 225-30, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19700373

RESUMO

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.


Assuntos
Anticonvulsivantes/uso terapêutico , Bacopa/química , Epilepsia , Hipocampo/metabolismo , Pilocarpina , Preparações de Plantas/uso terapêutico , Receptor 5-HT2C de Serotonina/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Carbamazepina/uso terapêutico , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Ergolinas/metabolismo , Hipocampo/efeitos dos fármacos , Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Ligação Proteica/efeitos dos fármacos , Ensaio Radioligante/métodos , Ratos , Ratos Wistar , Receptor 5-HT2C de Serotonina/genética , Antagonistas da Serotonina/metabolismo , Estatísticas não Paramétricas , Natação , Trítio/metabolismo
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