[Show abstract][Hide abstract] ABSTRACT: Salsolinol (SAL), a catechol isoquinoline has invited considerable attention due to its structural similarity with dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Its high endogenous presence in Parkinsonian brain implicated its possible association with the disease process. SAL is also present in alcohol beverages and certain food materials and can get access to brain especially in conditions of immature or impaired BBB. Besides this, the effect of SAL on neural stem cells (NSCs) which are potential candidates for adult neurogenesis and transplantation mediated rejuvenating attempts for Parkinson's disease (PD) brain has not been known so far. NSCs in both the cases have to overcome suppressive cues of diseased brain for their survival and function.
[Show abstract][Hide abstract] ABSTRACT: The present invention relates to bioactive extracts its fractions and isolation of compound from RauwolSa tetraphylla. The extracts and fractions are useful for the treatment of psychosis based on in-vivo validation on animal model and proportional binding affinities for dopaminergic - D2, Cholinergic (muscarinic) and Serotonergic (5HT2A) receptors for antipsychotic activity. The present invention relates to novel antipsychotic activity in the leaf alkaloids of Formula 1 and 2 named tetrahydroalstonine, 10-methoxytetrahydroalstonine, isoreserpiline, 10- derαethoxyreserpiline, 11-demethoxyreserpiline, reserpiline and α -yohimbine. The present invention also relates to processes for obtaining antipsychotic extracts as well as for the isolation of alkaloids of formula 1 and 2 from the leaves of Rauwolfia tetraphylla. The present invention particularly relates to significant antipsychotic activity in the MeOH extract, ethylacetate and chloroform fractions of R. tetraphylla and in the isolated compounds α -yohimbine, reserpiline and in a mixture 10- demethoxyreserpiline and 11-demethoxyreserpiline in 1:1.5 ratios for treating psychosis without any extra pyramidal symptoms (EPS).►1. R1=R2 = OMe R3 = α-H (Isoreserpiline) ► 2. R1=R2 = OMe R3 = β-H (Reserpiline) "3. R1 = OMe R2 = HR3 = β-H (11-Demethoxy reserpiline) "4. R1 = H R2 = OMe R3 = β-H (10-Demethoxy reserpiline) "5. R1 = R2 = H R3 = α -H (Tetrahydroalstonine) * 7. R1 = OMe R2 = H R3 = α -H (10-Methoxytetrahudroalstonine)
[Show abstract][Hide abstract] ABSTRACT: Neural progenitor cell transplantation has emerged as a promising approach for cell replacement therapy in the brain of neurodegenerative diseases. These are multipotent stem cells with self-renewal capabilities and can give rise to cells of all the three lineages of nervous system and can be maintained and differentiated to desirable neuronal subtypes in vitro with known trophic factors. However, like fetal cells, neural progenitor cells after differentiating to specific neuronal type also require continuous neurotrophic factor support for their long-term survival following transplantation. Recent reports suggest that olfactory ensheathing cells are capable of providing continuous neurotrophic factor to the transplanted neural progenitor cells for their long-term survival. In the present investigation, an attempt has been made to validate functional restoration in kainic acid lesioned rat model of cognitive dysfunction following co-transplantation of neural progenitor cells with olfactory ensheathing cells.Animals lesioned with kainic acid in CA3 subfield of hippocampal region were transplanted with neural progenitor cells, olfactory ensheathing cells or neural progenitor cells + olfactory ensheathing cells together. Twelve weeks post-transplantation functional restoration was assessed using neurobehavioral, neurochemical, and immunohistochemical approaches. Significant recovery in learning and memory (89%) was observed in co-transplanted group when compared to lesioned group. This was accompanied by significantly higher expression of choline acetyltransferase and restoration in cholinergic receptor binding in co-transplanted group (61%) over the animals transplanted either olfactory ensheathing cells or neural progenitor cells alone. Role of olfactory ensheathing cells in supplementing neurotrophic factors was further substantiated in vitro by pronounced differentiation of neural progenitor cells to choline acetyltransferase/acetylcholine esterase immunoreactive cells when co-cultured with olfactory ensheathing cells as compared to neural progenitor cells alone. The results strengthened the hypothesis that co-transplantation of olfactory ensheathing cells and neural progenitor cells may be a better approach for functional restoration in kainic acid induced rat model of cognitive dysfunction.
No preview · Article · Sep 2008 · International Journal of Developmental Neuroscience
[Show abstract][Hide abstract] ABSTRACT: During transplantation of VMC in Parkinson's disease their degeneration is very high due to lack of trophic support and mismatch conditions. To overcome this problem, Glial cell line-derived Neurotrophic Factor (GDNF) known to increase the functional viability and regeneration of dopaminergic cells. In the present study an attempt has been made to validate the role of GDNF cotransplanted with fetal VMC in functional restoration in rat model of Parkinson's disease. A significant restoration was observed in apomorphine induced rotation in rats co transplanted with GDNF and VMC (66%) as compare to VMC alone (42%). Apomorphine induced locomotor activity was restored by 67, 38% in cotransplanted and VMC alone transplanted rats, respectively. Level of dopamine and 3,4 dihydroxy-phenyl acetic acid (DOPAC) in the striatum were significantly restored by 67 and 62, 42 and 33% in cotransplanted and VMC alone transplanted rats, respectively. A significant restoration was observed in striatum dopamine receptors by 69% in rats cotransplanted with VMC & GDNF, and 45% in those transplanted with VMC alone. GDNF alone transplantation did not show significant restoration in either of the parameters. Functional viabilty of dopaminergic neurons was further confirmed by Tyrosine Hydroxylase (TH) immunopositivity in striatal region where a significantly high expression was observed in cotransplanted animals when compared with VMC alone.Results of the present study suggests that cotransplantation of GDNF and VMC may help in better functional restoration in 6-OHDA lesioned rat model of Parkinson's disease studied at 4 weeks post transplantation.
Full-text · Article · Jun 2008 · Journal of Neurochemistry
[Show abstract][Hide abstract] ABSTRACT: Transplantation of neural stem cells (NSC) derived dopamine (DA) neurons has emerged as an alternative approach to fetal neural cell transplantation in Parkinson's disease (PD). However, similar to fetal neural cell, survival of these neurons following transplantation is also limited due to limited striatal reinnervation (graft with dense neuronal core), limited host-graft interaction, poor axonal outgrowth, lack of continuous neurotrophic factors supply and principally an absence of cell adhesion molecules mediated appropriate developmental cues. In the present study, an attempt has been made to increase survival and function of NSC derived DA neurons, by co-grafting with Zuckerkandl's organ (a paraneural organ that expresses neurotrophic factors as well as cell adhesion molecules); to provide continuous NTF support and developmental cues to transplanted DA neurons in the rat model of PD. 24 weeks post transplantation, a significant number of surviving functional NSC derived DA neurons were observed in the co-transplanted group as evident by an increase in the number of tyrosine hydroxylase immunoreactive (TH-IR) neurons, TH-IR fiber density, TH-mRNA expression and TH-protein level at the transplantation site (striatum). Significant behavioral recovery (amphetamine induced stereotypy and locomotor activity) and neurochemical recovery (DA-D2 receptor binding and DA and DOPAC levels at the transplant site) were also observed in the NSC+ZKO co-transplanted group as compared to the NSC or ZKO alone transplanted group. In vivo results were further substantiated by in vitro studies, which suggest that ZKO increases the NSC derived DA neuronal survival, differentiation, DA release and neurite outgrowth as well as protects against 6-OHDA toxicity in co-culture condition. The present study suggests that long-term and continuous NTF support provided by ZKO to the transplanted NSC derived DA neurons, helped in their better survival, axonal arborization and integration with host cells, leading to long-term functional restoration in the rat model of PD.
Full-text · Article · May 2008 · Experimental Neurology
[Show abstract][Hide abstract] ABSTRACT: In the present study, an attempt has been made to explore the neuroprotective and neuroreparative (neurorescue) effect of black tea extract (BTE) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In the neuroprotective (BTE + 6-OHDA) and neurorescue (6-OHDA + BTE) experiments, the rats were given 1.5% BTE orally prior to and after intrastriatal 6-OHDA lesion respectively. A significant recovery in d-amphetamine induced circling behavior (stereotypy), spontaneous locomotor activity, dopamine (DA)-D2 receptor binding, striatal DA and 3-4 dihydroxy phenyl acetic acid (DOPAC) level, nigral glutathione level, lipid peroxidation, striatal superoxide dismutase and catalase activity, antiapoptotic and proapoptotic protein level was evident in BTE + 6-OHDA and 6-OHDA + BTE groups, as compared to lesioned animals. BTE treatment, either before or after 6-OHDA administration protected the dopaminergic neurons, as evident by significantly higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons, increased TH protein level and TH mRNA expression in substantia nigra. However, the degree of improvement in motor and neurochemical deficits was more prominent in rats receiving BTE before 6-OHDA. Results suggest that BTE exerts both neuroprotective and neurorescue effects against 6-OHDA-induced degeneration of the nigrostriatal dopaminergic system, suggesting that possibly daily intake of BTE may slow down the PD progression as well as delay the onset of neurodegenerative processes in PD.
Full-text · Article · Jun 2006 · Neurobiology of Disease
[Show abstract][Hide abstract] ABSTRACT: An attempt has been made to compare the potentiality of readily available chemicals and their combinations as best storage/transport media for avulsed tooth. Cultured human periodontal ligament cells were exposed to either of tap water, human saliva, normal saline 0.9%, Dextrose solution 5.0%, Milk 0.5% or with combination of dextrose+normal saline (DNS) and DNS+milk 0.5% for a time range between 30 minutes to 96 hr at three different temperatures i.e., 4°C, 20°C and 37°C. Tetrazolium bromide salt (MTT) assay was selected as endpoint to assess the cell viability. It was observed in general that the survival rate was increased with the increase in temperature and highest at 37°C in all the storage media used except tap water. Tap water had a detrimental effect, whereas both the combinations "dextrose+normal saline (DNS) and DNS+milk 0.5%" were found best storage media to preserve significantly high viable cells than the other experimental solutions. Low-fat milk and dextrose solution 5% could serve as an alternative for short period of time at 370C, if the other solutions are not readily available.
No preview · Article · Jun 2005 · Journal of Ecophysiology and Occupational Health
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the in vitro attachment behavior of human periodontal ligament fibroblasts on periodontally involved root surface after conditioning with CO2 laser and to compare its efficacy with chemical conditioning agents, namely tetracycline hydrochloride, citric acid, hydrogen peroxide (H2O2) and EDTA, using scanning electron microscopy.
A total of 84 scaled and root-planed specimens from periodontally involved single-rooted human teeth showing hopeless prognosis were selected and assigned to two groups. One group was lased with a CO2 laser (from 5 cm at 3 W for 0.8, 1.0 and 1.2 s), and the other group was treated with either tetracycline hydrochloride (2.5%), citric acid (saturated solution, pH 1), H2O2 (6%) or EDTA (5%; pH 7.4) for 3 min. The specimens were then seeded with human periodontal ligament fibroblasts, incubated for either 12 h or 24 h, and then the cell attachment behavior was observed.
CO2 laser irradiation for 1.0 s was found to be the most efficient, showing consistently good cell attachment with the highest mean value (15.00 +/- 3.41 cells/10,000 microm2 after incubation for 12 h and 29.17 +/- 2.04 cells/10,000 microm2 after 24 h), followed by irradiation for 0.8 s (13.11 +/- 3.04 cells/10,000 microm2 after incubation for 12 h and 22.91 +/- 7.10 cells/10,000 microm2 after 24 h). Charring was observed following irradiation for 1.2 s. Amongst chemical conditioning agents, citric acid was found to be the most efficient, with a mean cell attachment of 17.82 +/- 2.16 cells/10,000 microm2 after incubation for 12 h and 23.62 +/- 1.94 cells/10,000 microm2 after 24 h. EDTA and H2O2 did not do well in the study.
The results suggest that CO2 laser irradiation for 1.0 s may promote comparatively better attachment of periodontal ligament fibroblast on dentinal root surfaces than the conventional chemical conditioning agents used in the study.
No preview · Article · Jan 2005 · Journal of Periodontal Research
[Show abstract][Hide abstract] ABSTRACT: Free radical mediated damage has been reported to contribute significantly towards low survival (5-10%) of grafted dopaminergic neurons, post transplantation. In the present study, an attempt has been made to explore the neuroprotective potential of the combination of two major antioxidants ascorbic acid (AA) and glutathione (GSH) on ventral mesencephalic cells (VMC) and nigral dopamine (DA) neurons when co-transplanted together with VMC in rat model of Parkinson's disease (PD). GSH and AA have been reported to act co-operatively in the conditions of oxidative stress thereby helping in maintaining the cellular GSH/GSSG redox status. Functional recovery was assessed 12 weeks post transplantation, where a significant restoration (p<0.001) in d-amphetamine induced circling behavior (62%), spontaneous locomotor activity (SLA; 64%), dopamine-D2 receptor binding (63%), dopamine (65%) and 3,4-dihydroxy phenyl acetic acid (DOPAC) level (64%) was observed in co-transplanted animals as compared to lesioned and VMC alone grafted rats. VMC and GSH+AA co-transplanted animals exhibited a significantly higher surviving TH-immunoreactive (TH-ir) neurons number (p<0.01), TH-ir fibers outgrowth (p<0.05) in striatal graft and TH-ir neurons in substantia nigra pars compacta (SNpc) (p<0.01), as compared to VMC alone transplanted rats. An attempt was made to further confirm our in vivo observations through in vitro experiments where following in vitro exposure to 6-OHDA, a higher cell survival (p<0.01), TH-ir cell counts (p<0.001) and DA and DOPAC levels (p<0.01) were also observed in 8-day-old VMC culture in presence of GSH+AA as compared to VMC cultured in absence of antioxidants. The results suggest that GSH+AA when co-transplanted with VMC provide higher restoration probably by increasing the survival of grafted VMC and simultaneously supporting nigral TH-immunopositive neurons in rat model of PD.
Full-text · Article · Dec 2004 · Journal of Chemical Neuroanatomy
[Show abstract][Hide abstract] ABSTRACT: Exogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study the functional restoration following co-transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co-transplanted animals at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA-D(2) receptor binding (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-immunoreactive (IR) fiber density in striatum, as well as TH-IR neurons in substantia nigra pars compacta in co-transplanted animals over VMC-transplanted animals. The result suggests that co-transplantation of CB cells along with VMC provides better and long-term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons.
Full-text · Article · Nov 2004 · Journal of Neurochemistry
[Show abstract][Hide abstract] ABSTRACT: Different strategies have been worked out to promote survival of transplanted fetal ventral mesencephalic cells (VMCs) using trophic and nontrophic support. Olfactory ensheathing cells (OECs) express high level of growth factors including NGF, bFGF, GDNF, and NT3, which are known to play important role in functional restoration or neurodegeneration. In the present investigation, an attempt has been made to study functional restoration in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) following cotransplantation of VMC and OECs (cultured from olfactory bulb, OB) in striatal region. The functional restoration was assessed using neurobehavioral, neurochemical, and immunohistochemical approach. At 12 weeks, post-transplantation, a significant recovery (P < 0.001) in D-amphetamine induced circling behavior (73%), and spontaneous locomotor activity (SLA, 81%) was evident in cotransplanted animals when compared with 6-OHDA-lesioned animals. A significant restoration (P < 0.001) in [3H]-spiperone binding (77%), dopamine (DA) (82%) and 3,4-dihydroxy phenyl acetic acid (DOPAC) level (75%) was observed in animals cotransplanted with OECs and VMC in comparison to lesioned animals. A significantly high expression and quantification of tyrosine hydroxylase (TH)-positive cells in cotransplanted animals further confirmed the supportive role of OECs in viability of transplanted dopaminergic cells, which in turn may be helping in functional restoration. This was further substantiated by our observation of enhanced TH immunoreactivity and differentiation in VMC cocultured with OECs under in vitro conditions as compared to VMC alone cultures. The results suggest that cotransplantation of OECs and VMC may be a better approach for functional restoration in 6-OHDA-induced rat model of Parkinson's disease.
Full-text · Article · Aug 2004 · Neurobiology of Disease
[Show abstract][Hide abstract] ABSTRACT: Pyrethroid-based mosquito repellents (MR) are commonly used to protect humans against mosquito vector. New born babies and children are often exposed to pyrethroids for long periods by the use of liquid vaporizers. Occupational and experimental studies indicate that pyrethroids can cause clinical, biochemical and neurological changes, and that exposure to pyrethroids during organogenesis and early developmental period is especially harmful. The neurotoxicity caused by MR has aroused concern among public regarding their use. In the present study, the effect of exposure of rat pups during early developmental stages to a pyrethroid-based MR (allethrin, 3.6% w/v, 8h per day through inhalation) on blood-brain barrier (BBB) permeability was investigated. Sodium fluororescein (SF) and Evan's blue (EB) were used as micromolecular and macromolecular tracers, respectively. Exposure during prenatal (gestation days 1-20), postnatal (PND1-30) and perinatal (gestation days 1-20 + PND1-30) periods showed significant increase in the brain uptake index (BUI) of SF by 54% (P < 0.01), 70% (P < 0.01), 79% (P < 0.01), respectively. This increase persisted (68%, P < 0.01) even 1 week after withdrawal of exposure (as assessed on PND37). EB did not exhibit significant change in BBB permeability in any of the group. The results suggest that MR inhalation during early prenatal/postnatal/perinatal life may have adverse effects on infants leading to central nervous system (CNS) abnormalities, if a mechanism operates in humans similar to that in rat pups.
Full-text · Article · Feb 2004 · International Journal of Developmental Neuroscience