Nurr1 regulates RET expression in dopamine neurons of adult rat midbrain

• DOI: 10.1111/j.1471-4159.2010.06841.x
• Publication Date: 2010-06-02T05:33:50Z
• Authors: Danny Galleguillos; José A. Fuentealba; Luis M. Gómez; Mathias Saver; Andrea Gómez; Kevin Nash; Corinna Burger; Katia Gysling; María E. Andrés
• Keywords: Male; Neurons; Transcriptional Activation; 0303 health sciences; Dopamine; Proto-Oncogene Proteins c-ret; Down-Regulation; Response Elements; Transfection; Rats; DNA-Binding Proteins; Rats, Sprague-Dawley; Substantia Nigra; 03 medical and health sciences; Gene Expression Regulation; Mesencephalon; 03 Salud y bienestar; Nuclear Receptor Subfamily 4, Group A, Member 2; Animals; Humans; 03 Good Health and Well-being; RNA, Messenger; Promoter Regions, Genetic

J. Neurochem. (2010) 114 , 1158–1167. Abstract Genesis of midbrain dopamine (DA) neurons depends on Nurr1, a nuclear receptor expressed during development and adulthood in these neurons. Nurr1 is required for the expression genes dopaminergic phenotype such as tyrosine hydroxylase DA transporter. The kinase RET also development. However, it unknown whether regulated by adulthood, mechanism which regulates expression. Using an adeno‐associated vector‐delivered anti‐Nurr1 ribozyme, we knocked‐down unilaterally substantia nigra (SN) adult rats. Animals injected with ribozyme displayed 57.3% decrease mRNA SN accompanied decreased extracellular levels striatum. protein ipsilateral striatum 76.9% 47%, respectively. Tyrosine transporter did not change SN. induced transcription human promoter cell type concentration‐dependent manner. induction independent NBRE elements. These results show that rat suggest transcriptional target this receptor.