The effect of bacterial contamination on the neurodegeneration phenotype of the Drosophila melanogaster SCA3 model upon antibiotic treatment or induction of hydrogen sulfide biosynthesis pathway.

Grotenhuis, K.A. (Kai-Anne) (2014) The effect of bacterial contamination on the neurodegeneration phenotype of the Drosophila melanogaster SCA3 model upon antibiotic treatment or induction of hydrogen sulfide biosynthesis pathway. thesis, Medicine.

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Abstract

Spinocerebellar ataxia 3 (SCA3) is a heritable neurodegenerative polyglutamine (polyQ) disease that is associated with aggregate formation in neurons. It has been previously shown that the Drosophila melanogaster model of SCA3 possesses an eye degeneration phenotype. In the lab of Prof. Sibon, the presence of bacteria has been demonstrated on the surface of some of affected eyes. In this research, we investigate the effect of two interventions on the eye phenotype, the presence of bacteria and the immune response: treatment with the antibiotic ampicillin by supplementing it to the fly food or upregulation of hydrogen sulfide biosynthesis pathway (H2S) by overexpressing hydrogen sulfide producing enzyme cystathionine-γ-lyase (CSE). The bacteria on the eye surface can be eliminated by the cellwall destructive abilities of ampicillin. H2S can inhibit expression of pro-inflammatory factors, next to its anti-apoptotic and neuroprotective properties. Also, the effect of both interventions on the immune response genes is studied. This study reveals that neither ampicillin nor CSE has an effect on the eye phenotype. These treatments also do not reduce the percentage of eyes with bacteria on the surface suggesting that ampicillin is not efficient against these bacteria and overexpression of CSE in the eye does not protect it from bacterial colonization. Overexpression of the polyQ protein leads to an increase in immune response genes, which is reversed by the overexpression of CSE. This implies that the initial increase in the immune response in the Drosophila SCA3 model and its decrease upon overexpression of CSE is not associated with bacterial colonization on the eye surface. Treatment with ampicillin does not have an effect on the immune response genes. To investigate the actual effect of bacteria on the eye phenotype in Drosophila, further research with an improved method of eradicating bacteria should be performed.

Item Type:	Thesis (Thesis)
Supervisor name:	Sibon, Prof. Dr. O.C.M. and Baratashvili, M.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:49
Last Modified:	25 Jun 2020 10:49
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1024

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