Jyothi Prasad (Research Fellow) presented her seminar on "Animal Models of Parkinson's Disease".
Aphang (1st year PhD scholar) presented the paper by A.B. Muñoz-Manchado et al. from Neurobiology of Aging, 2013 titled "Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson’s disease"
ABSTRACT Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches toParkinson's disease. Vidyadhara D J (1st year PhD Scholar) presented a paper by Angot et al titled "Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo" from the journal PLOSone (2012).
Abstract: Several people with Parkinson’s disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture. Alpha-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of alpha-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred alpha-synuclein. We now demonstrate frequent transfer of alpha-synuclein from a rat brain engineered to overexpress human alpha-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of alpha-synuclein. Thus, we present evidence both for the involvement of endocytosis in alpha-synuclein uptake in vivo. and for seeding of aggregation of endogenous alpha-synucleln in the recipient neuron by the transferred 2-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted alpha-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of alpha-synuclein and therefore might retard progression of Parkinson neuropathology. Yarreiphang (UGC Junior Research Fellow) presented a paper by M. Sonia Angeline et al.in the journal Neuroscience(2012) titled 'Rotenone-induced parkinsonism elicits behavioral impairments and differential expression of parkin, heat shock protein and caspases in the rats"
Abstract—Rotenone is a pesticide that inhibits mitochondrial complex I activity, thus creating an environment of oxidative stress in the cell. Many studies have employed rotenone to generate an experimental animal model of Parkinson’s disease (PD) that mimics and elicits PD-like symptoms, such as motor and cognitive decline. Cytoprotective proteins including parkin and heat shock proteins (HSPs) play major roles in slowing PD progression. Moreover, evidence suggests that mitochondrial dysfunction and oxidative stress-dependent apoptotic pathways contribute to dopaminergic neuron degeneration In PD. Here, rats were chronically exposed to rotenone to confirm that it causes a debilitating phenotype and various behavioral defects. We also performed histopathological examinations of nigrostriatal, cortical and cerebellar regions of rotenone-treated brain to elucidate a plausible neurodegenerative mechanism. The results of silver, tyrosine hydroxylase (TH), park in, ubiquitin and caspase staining of brain tissue sections further validated our findings. The stress response is known to trigger HSP In response to pharmacological insult. These protective proteins help maintain cellular homeostasis and may be capable of rescuing cells from death. Therefore, we assessed the levels of different HSPs in the rotenone-treated animals. Collectively, our studies indicated the following findings in the striatum and substantia nigra following chronic rotenone exposure in an experimental PD model: (i) behavioral deficit that correlated with histopathological changes and down regulation of TH signaling, (ii) decreased levels of the cytoprotective proteins parkin, DJI and Hsp7O and robust expression of mitochondrial chaperone Hsp6O according to Western blot, (iii) increased immunoreactivity for caspase 9, caspase 3 and ubiquitin and decreased parkin immunoreactivity. The presentation was neat and drew in valuable discussion among the listeners. The paper tried to emphasize that rotenone-induced Parkinson's disease model in rats, brings out the role of molecular mechanisms like that of HSPs (Heat shock proteins), which could be a potential target for therapeutic interventions. Some interesting thoughts were:
"Effect of a single dose of standard levodopa on cardiac autonomic function in Parkinson's disease" by SJ Sriranjini, Mohan Ganesan, Karuna Datta, Pramod Kumar Pal, Talakad N Sathyaprabha was published in Neurology India. Year : 2011 | Volume : 59 | Issue : 5 | Page : 659-663
ABSTRACT Background: Parkinson's disease (PD) is associated with autonomic dysfunction and chronic levodopa therapy has been reported to impair the autonomic control of heart rate. Aim: Our aim was to assess the immediate effect of a single dose of levodopa on heart rate variability (HRV) in idiopathic PD. Materials and Methods: Eleven patients of idiopathic PD (F:M =2:9, mean age 57.3±8.6 years, duration of illness 4.1±2.8 years, Hoehn and Yahr stage 2.1±0.2) on stable levodopa dosage were studied. Motor part of unified Parkinson's disease rating scale and resting Lead II electrocardiogram (ECG) recordings were performed at baseline (12 hours off medication) and after two tablets of 100/10 mg of standard levodopa/ carbidopa. ECG was recorded continuously in the first hour (H1) followed by a 15-min recording in second (H2), third (H3) and fourth (H4) hours. Artifact free 5-min segments of the ECG were analyzed offline to obtain the HRV parameters in time domain (ms) and frequency domains (ms 2 ). Results: Significant increase was observed in standard deviation of normal to normal intervals (23.5±2.7-46.2±6.6,P<0.05), root mean square of successive differences of NN intervals (16.3±2.9-30.7±5.1, P<0.01), total power (568.9±125.7-2739±667.5, P<0.01), low frequency power (146.5±40.8-614.1±206.7, P<0.05) and high frequency power (107.4±33.9-332.7±85.9, P<0.05) in H1. Conclusion: The results are suggestive of an improvement in the overall variability of the heart rate indicating an enhanced vagal tone. Keywords: Cardiac autonomic dysfunction, levodopa, Parkinson′s disease How to cite the article: Sriranjini SJ, Ganesan M, Datta K, Pal PK, Sathyaprabha TN. Effect of a single dose of standard levodopa on cardiac autonomic function in Parkinson's disease. Neurol India 2011;59:659-63 |
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