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Title: Telmisartan ameliorates dopaminergicand astrocytic functions against MPTP induced parkinsonism in experimental mice models
Researcher: Sathiya, S
Guide(s): Saravana Babu, C
Keywords: Telmisartan MPTP astrocyte dopaminergic interactions motor function Parkinsons disease
University: Dr. M.G.R. Educational and Research Institute
Completed Date: 04/06/2015
Abstract: Parkinsons disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in substantia nigra pars compacta and depletion of dopamine in striatum Existence of intense hyperactivated glial cells such as astrocytes and microglia is a hallmark pathophysiology in PD This reveals that restoration of dopaminergic functions alone may not be sufficient in the management of PD Various treatment strategies are available but none has curative effect or functions without side effects on long term exposure Evidences have shown that renin angiotensin system plays a major role in both glial and neuronal functions The present study was aimed to investigate the effects of telmisartan an angiotensin II type one receptor blocker on MPTP intoxicated acute and chronic mice models of PD with respect to the glial neuronal functions In acute model mice were intoxicated with MPTP eighty mg kg to induce neurodegeneration TEL was administered one hour prior to first MPTP injection and thereafter for two consecutive days In chronic model mice were injected with MPTP two and fifty mg kg along with probenecid two and fifty mg kg Probenecid was used to decrease the renal excretion of MPTP and its metabolite MPP thereby maintaining the effects of the neurotoxin during three point five days injection interval TEL was challenged against MPTP intoxication and administered one hour prior to first MPTP injection and thereafter daily once till completion of the experiment The neuroprotective effects of TEL against MPTP induced motor dysfunctions and dopaminergic degeneration were ascertained through investigating the alterations in dopamine transporters tyrosine hydroxylase expressions mutant protein alpha synuclein and neurotransmitters dopamine and its metabolites three comma four Dihydroxyphenylacetic acid and homovanillic acid contents in mice Further the role of TEL on glial markers glial fibrillary acidic protein and glial derived neurotrophic factor oxidative stress markers reduced glutathione nitric oxide and inducible nitric oxide synthase and inflammatory markers tumor necrosis factor alpha and interleukin one beta were also studied in SNpc and ST regions of MPTP mice brain TEL administration restored the motor functions which was further supported by the significant increase in dopamine DOPAC and HVA levels It upregulates DAT and TH and down regulates alpha syn expression in both acute and chronic MPTP models This restoration of dopaminergic function by TEL highly correlates with the decreased glial and inflammatory markers and increased anti oxidant stature partly in acute state and considerably higher in chronic stage of PD Present study clearly revealed that TEL not only restores dopaminergic functions but also alleviates astrocytic dysfunctions in PD The results obtained from the present study establishes the neuroprotective effect of TEL in an acute and chronic model of Parkinsonism with respect to the astrocytic dopaminergic association and adds evidence to the disease modifying therapeutic potential of central ATIR antagonism
Appears in Departments:Department of Biotechnology

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