Transcription Factors Phox2a/2b Upregulate Expression of Noradrenergic and Dopaminergic Phenotypes in Aged Rat Brains
- PDF / 1,499,381 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 3 Downloads / 164 Views
ORIGINAL ARTICLE
Transcription Factors Phox2a/2b Upregulate Expression of Noradrenergic and Dopaminergic Phenotypes in Aged Rat Brains Yan Fan 1,2 & Fei Zeng 1,3 & Russell W. Brown 1 & Jennifer B. Price 4 & Thomas C. Jones 4 & Meng-Yang Zhu 1 Received: 28 March 2020 / Revised: 30 May 2020 / Accepted: 25 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The present study investigated the effects of forced overexpression of Phox2a/2b, two transcription factors, in the locus coeruleus (LC) of aged rats on noradrenergic and dopaminergic phenotypes in brains. Results showed that a significant increase in Phox2a/ 2b mRNA levels in the LC region was paralleled by marked enhancement in expression of DBH and TH per se. Furthermore, similar increases in TH protein levels were observed in the substantial nigra and striatum, as well as in the hippocampus and frontal cortex. Overexpression of Phox2 genes also significantly increased BrdU-positive cells in the hippocampal dentate gyrus and NE levels in the striatum. Moreover, this manipulation significantly improved the cognition behavior. The in vitro experiments revealed that norepinephrine treatments may increase the transcription of TH gene through the epigenetic action on the TH promoter. The results indicate that Phox2 genes may play an important role in improving the function of the noradrenergic and dopaminergic neurons in aged animals, and regulation of Phox2 gene expression may have therapeutic utility in aging or disorders involving degeneration of noradrenergic neurons. Keywords Tyrosine hydroxylase . Dopamine-β-hydroxylase . Locus coeruleus . Dopamine . Neurogenesis . Morris water maze
Abbreviation AD Alzheimer’s disease BrdU 5-Bromo-2-deoxyuridine ChIP Chromatin immunoprecipitation assay DA Dopamine DBH Dopamine-β-hydroxylase DG Dentate gyrus ECL Enhanced chemiluminescence FBS Fetal bovine serum FC Frontal cortex GCL Granule cell layer
* Meng-Yang Zhu [email protected] 1
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
2
Department of Biochemistry, Nantong University College of Medicine, Nantong, China
3
Department of Neurology, Remin Hospital of the Wuhan University, Wuhan, China
4
Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN, USA
HPLC HP LC MWM NE PBS PD qPCR SDS SN Sp1 TH VTA
High-performance liquid chromatography Hippocampus Locus coeruleus Morris water maze Norepinephrine Phosphate-buffer saline Parkinson’s disease Quantitative real-time polymerase chain reaction Sodium lauryl sulfate Substantia nigra Specificity protein 1 Tyrosine hydroxylase Ventral tegmental area
Introduction The locus coeruleus (LC) is the primary source of norepinephrine (NE) in brains. The LC not only sends ascending projections to the cortex and hippocampus (HP), NE arising from the LC also influences activity of the substantia nigra (SN) and ventral tegmental area (VTA) by enhancing the release of dop
Data Loading...
