Long-term controlled GDNF over-expression reduces dopamine transporter activity without affecting tyrosine hydroxylase expression in the rat mesostriatal system

Neurobiology of Disease
Pedro Barroso-ChineaTomás González-Hernández

Abstract

The dopamine (DA) transporter (DAT) is a plasma membrane glycoprotein expressed in dopaminergic (DA-) cells that takes back DA into presynaptic neurons after its release. DAT dysfunction has been involved in different neuro-psychiatric disorders including Parkinson's disease (PD). On the other hand, numerous studies support that the glial cell line-derived neurotrophic factor (GDNF) has a protective effect on DA-cells. However, studies in rodents show that prolonged GDNF over-expression may cause a tyrosine hydroxylase (TH, the limiting enzyme in DA synthesis) decline. The evidence of TH down-regulation suggests that another player in DA handling, DAT, may also be regulated by prolonged GDNF over-expression, and the possibility that this effect is induced at GDNF expression levels lower than those inducing TH down-regulation. This issue was investigated here using intrastriatal injections of a tetracycline-inducible adeno-associated viral vector expressing human GDNF cDNA (AAV-tetON-GDNF) in rats, and doxycycline (DOX; 0.01, 0.03, 0.5 and 3mg/ml) in the drinking water during 5weeks. We found that 3mg/ml DOX promotes an increase in striatal GDNF expression of 12× basal GDNF levels and both DA uptake decrease and TH down-regulati...Continue Reading

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Citations

Sep 13, 2016·Neurobiology of Disease·Deniz KirikÅsa Petersén
Dec 15, 2020·Biomaterials Science·João ConniotJoão Conde
Jan 24, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Diego Luis-RaveloTomas Gonzalez-Hernandez
Apr 16, 2021·PLoS Genetics·Alvaro Ingles-PrietoHarald Janovjak

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