title: Differential distribution of hypoxia-inducible factor 1-beta (ARNT or ARNT2) in mouse substantia nigra and ventral tegmental area.
abstract: Hypoxia has been proposed as a mechanism underlying gene-environment interactions in the neurodevelopmental model of schizophrenia, and hypoxia-inducible factor 1 (HIF-1) could mediate the interactions. In the current study, we analyzed the HIF-1 beta subunit, as formed by aryl hydrocarbon receptor nuclear translocator (ARNT) or ARNT2, in the mouse substantia nigra (SN) and the ventral tegmental area (VTA). We performed immunohistochemical studies of ARNT and ARNT2 in the adult mouse brain, and colocalization analyses, with specific emphasis on dopaminergic cells, i.e. tyrosine hydroxylase (TH) immunoreactive cells. Bioinformatic analyses identified shared protein partners for ARNT and ARNT2. ARNT immunoreactivity showed widespread neuronal labeling without overt regional specificity. We observed co-localization of ARNT and TH in the SN compacta and VTA. Nuclei strongly labeled for ARNT2 were observed in the SN reticulata, while only weak immunoreactivity for ARNT2 was found in TH-immunoreactive neurons in SN compacta and VTA. Stereological analysis showed that ARNT was preferentially expressed in dopaminergic neurons in SN compacta and VTA. Nuclei strongly labeled for ARNT2 were present in neocortex and CA1 of hippocampus. Differential expression of ARNT and ARNT2 in dopaminergic neurons may relate to the vulnerability of distinct dopaminergic projections to hypoxia and to functional vulnerability in schizophrenia and other neuropsychiatric disorders.
authors.affiliation: School of Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, Netherlands; Department of Psychology, Neuropsychology Doctoral Subprogram, The City University of New York (CUNY) Graduate Center, New York, NY, USA.
authors.forename: J A D
authors.initials: JA
authors.lastname: Dela Cruz
authors.affiliation: School of Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, Netherlands; C.E. Schmidt College of Medicine, Florida Atlantic University (FAU), Boca Raton, FL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Schmidt-Kastner
authors.affiliation: School of Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: J A A
authors.initials: JA
authors.lastname: Stevens
authors.affiliation: School of Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: H W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: School of Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Maastricht, Netherlands. Electronic address: b.rutten@maastrichtuniversity.nl.
authors.forename: B P F
authors.initials: BP
authors.lastname: Rutten
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000032:analysis* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013378:Substantia Nigra / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; C497397:Arnt protein, mouse; C099817:Arnt2 protein, mouse
keywords: Aryl hydrocarbon receptor nuclear translocator; Dopamine; HIF-1; Hypoxia; Schizophrenia; Tyrosine hydroxylase