Ser31 tyrosine hydroxylase phosphorylation parallels differences in dopamine recovery in nigrostriatal pathway following 6-OHDA lesion

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Abstract

Compensatory mechanisms in dopamine (DA) signaling have long been proposed to delay onset of locomotor symptoms during Parkinson's disease progression until ∼80% loss of striatal DA occurs. Increased striatal dopamine turnover has been proposed to be a part of this compensatory response, but may occur after locomotor symptoms. Increased tyrosine hydroxylase (TH) activity has also been proposed as a mechanism, but the impact of TH protein loss upon site-specific TH phosphorylation in conjunction with the impact on DA tissue content is not known. The tissue content of DA was determined against TH protein loss in the striatum and substantia nigra (SN) following 6-hydroxydopamine lesion in the medial forebrain bundle in young Sprague-Dawley male rats. Although DA predictably decreased in both regions following 6-hydroxydopamine, there was a significant difference in DA loss between the striatum (75%) and SN (40%), despite similar TH protein loss. Paradoxically, there was a significant decrease in DA against remaining TH protein in striatum, but a significant increase in DA against remaining TH in SN. In the SN, increased DA per remaining TH protein was matched by increased ser31, but not ser40, TH phosphorylation. In striatum, both ser31 and ser40 phosphorylation decreased, reflecting decreased DA per TH. However, in control nigral and striatal tissue, only ser31 phosphorylation correlated with DA per TH protein. Combined, these results suggest that the phosphorylation of ser31 in the SN may be a mechanism to increase DA biosynthesis against TH protein loss in an in vivo model of Parkinson's disease.

Original languageEnglish
Pages (from-to)548-558
Number of pages11
JournalJournal of Neurochemistry
Volume129
Issue number3
DOIs
StatePublished - May 2014

Keywords

  • 6-OHDA
  • Parkinson's disease
  • dopamine
  • nigrostriatal
  • substantia nigra
  • tyrosine hydroxylase

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