Tyvitumakkeiden GABAergisen neurotransmission adaptiiviset muutokset Parkinsonin taudissa

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http://urn.fi/URN:NBN:fi-fe201801151276
Title: Tyvitumakkeiden GABAergisen neurotransmission adaptiiviset muutokset Parkinsonin taudissa
Author: Kontti, Arttu
Contributor: University of Helsinki, Faculty of Pharmacy
Publisher: Helsingfors universitet
Date: 2014
Language: fin
URI: http://urn.fi/URN:NBN:fi-fe201801151276
http://hdl.handle.net/10138/144178
Thesis level: master's thesis
Discipline: Farmakologi
Pharmacology
Farmakologia
Abstract: Parkinson's disease causes changes in the basal ganglia GABAergic neurotransmission in addition to the well-known dopaminergic changes. These GABAergic modulations may cause somed of the symptoms not responding well to the standard dopaminergic medication. Neurotrophic factors are a group of endogenous proteins showing promise as a future treatment for Parkinson's disease. They are known to have neuroprotective and neurorestorative effects on the dopaminergic cells. Their effects to the GABAergic cells are still mostly unknown. Intrastriatal injection of GDNF to rats caused significantly slower weight gain compared to CDNF, MANF one week after stereotaxic operation (p=0,002 for CDNF vs. GDNF and p<0,001 for MANF vs. GDNF). Difference to the vehicle (phosphate buffered saline) used as a negative control was not statistically significant (p=0,055). Three weeks after the operation the differences between the treatment groups were no longer statistically significant. Because of problems with the separation in analysis, microdialysis samples remain still to be analysed. To help the analysis of GABA in the future we determined the analytical parameters of the analytical apparatus. We also defined differences in probe permeability between 1 mm and 2 mm probes and between old and new batches. GABA analysis was performed with a HPLC-fluorometric detection of o-phtaldialdehyde-derived GABA. Detection limit for old apparatus was 7,2 nM and for new apparatus 6,2 nM in a sample of 15 µl (0,11 pmol and 93 fmol respectively). Quantification limits defined were 22 nM and 19 nM (0,33 pmol and 0,28 pmol) for the old and the new apparatus, respectively. Upper limit of quantification was estimated to be 246 nM (3,7 pmol). Probes had significant differences in permeability between 1 mm and 2 mm probes, as well as between batches. The variance of permeability of 1 mm probes was estimated to be approximately twofold compared to the 2 mm probes. Furthermore the permeability of 1 mm probes varied between batches significantly. An average of permeability of the old batch was 34 % lower than that of a new batch (p<0,001).
Subject: GDNF
CDNF
MANF
GABA
Parkinson's disease
Basal ganglia
Neurotrophic factors
Microdialysis
HPLC


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