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Neuronal activity regulates expression of tyrosine hydroxylase in adult mouse substantia nigra pars compacta neurons

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dc.contributor.authorAumann, T.D.
dc.contributor.authorEgan, K.
dc.contributor.authorLim, J.
dc.contributor.authorBoon, W.C.
dc.contributor.authorBye, C.R.
dc.contributor.authorChua, H.K.
dc.contributor.authorBaban, N.
dc.contributor.authorParish, C.L.
dc.contributor.authorBobrovskaya, L.
dc.contributor.authorDickson, P.
dc.contributor.authorHorne, M.K.
dc.date.issued2011
dc.descriptionLink to a related website: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1471-4159.2010.07151.x, Open Access via Unpaywall
dc.description.abstractStriatal delivery of dopamine (DA) by midbrain substantia nigra pars compacta (SNc) neurons is vital for motor control and its depletion causes the motor symptoms of Parkinson’s disease. While membrane potential changes or neuronal activity regulates tyrosine hydroxylase (TH, the rate limiting enzyme in catecholamine synthesis) expression in other catecholaminergic cells, it is not known whether the same occurs in adult SNc neurons. We administered drugs known to alter neuronal activity to mouse SNc DAergic neurons in various experimental preparations and measured changes in their TH expression. In cultured midbrain neurons, blockade of action potentials with 1 lM tetrodotoxin decreased TH expression beginning around 20 h later (as measured in real time by green fluorescent protein (GFP) expression driven off TH promoter activity). By contrast, partial blockade of small-conductance, Ca2+-activated potassium channels with 300 nM apamin increased TH mRNA and protein between 12 and 24 h later in slices of adult midbrain. Twoweek infusions of 300 nM apamin directly to the adult mouse midbrain in vivo also increased TH expression in SNc neurons, measured immunohistochemically. Paradoxically, the number of TH immunoreactive (TH+) SNc neurons decreased in these animals. Similar in vivo infusions of drugs affecting other ion-channels and receptors (L-type voltage-activated Ca2+ channels, GABAA receptors, high K+, DA receptors) also increased or decreased cellular TH immunoreactivity but decreased or increased, respectively, the number of TH+ cells in SNc. We conclude that in adult SNc neurons: (i) TH expression is activity-dependent and begins to change 20 h following sustained changes in neuronal activity; (ii) ion-channels and receptors mediating cell-autonomous activity or synaptic input are equally potent in altering TH expression; and (iii) activity-dependent changes in TH expression are balanced by opposing changes in the number of TH+ SNc cells.
dc.identifier.citationJournal of Neurochemistry, 2011; 116(4):646-658
dc.identifier.doi10.1111/j.1471-4159.2010.07151.x
dc.identifier.issn0022-3042
dc.identifier.issn1471-4159
dc.identifier.urihttps://hdl.handle.net/1959.8/124717
dc.language.isoen
dc.publisherWiley-Blackwell
dc.relation.fundingNHMRC
dc.relation.fundingCASS Foundation Limited
dc.relation.fundingBethlehem Griffiths Research Foundation
dc.rightsCopyright 2011 The Authors, International Society for Neurochemistry
dc.source.urihttps://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1471-4159.2010.07151.x
dc.subjectdopamine
dc.subjectmotor symptoms
dc.subjectnigrostriatal pathway
dc.subjectParkinson’s disease
dc.titleNeuronal activity regulates expression of tyrosine hydroxylase in adult mouse substantia nigra pars compacta neurons
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9915909114701831

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