Wednesday, August 26, 2015

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

 2015 Aug 19. pii: S0306-4522(15)00728-9. doi: 10.1016/j.neuroscience.2015.08.005. [Epub ahead of print]


Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced dopamine were not defined. In order to clarify the effects of infection on host dopamine biosynthetic enzymes and dopamine packaging we examined enzyme levels and activity and dopamine accumulation and release in T. gondii infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase and DOPA decarboxylase did not change significantly in infected cultures, DOPA decarboxylase was found within the parasitophorous vacuole, the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DOPA decarboxylase was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of dopamine within tissue cysts in infected brain as a parasite-encoded enzyme with tyrosine hydroxylase activity was also localized within tissue cysts. In contrast, cellular dopamine packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased dopamine was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated dopamine within dopaminergic cells without the toxic ramifications of free cytosolic dopamine. The mechanism for synthesis and packaging of dopamine by T. gondii infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.


Apicomplexa; Dopa decarboxylase; Manipulation; Neurotransmitter; Tyrosine hydroxylase
[PubMed - as supplied by publisher] 

1 comment:

Chloe said...

I think the article should be cited because it has introduced the issue in details. But I was wondering whether there are some substances can control the expression of genes that adapts the cellular condition to accommodate oxidative stress.