title: Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression.
abstract: The noradrenergic locus coeruleus (LC) is the principal source of brain norepinephrine, a neurotransmitter thought to play a major role in the pathology of major depressive disorder (MDD) and in the therapeutic action of many antidepressant drugs. The goal of this study was to identify potential mediators of brain noradrenergic dysfunction in MDD. Bone morphogenetic protein 7 (BMP7), a member of the transforming growth factor-β superfamily, is a critical mediator of noradrenergic neuron differentiation during development and has neurotrophic and neuroprotective effects on mature catecholaminergic neurons. Real-time PCR of reversed transcribed RNA isolated from homogenates of LC tissue from 12 matched pairs of MDD subjects and psychiatrically normal control subjects revealed low levels of BMP7 gene expression in MDD. No differences in gene expression levels of other members of the BMP family were observed in the LC, and BMP7 gene expression was normal in the prefrontal cortex and amygdala in MDD subjects. Laser capture microdissection of noradrenergic neurons, astrocytes, and oligodendrocytes from the LC revealed that BMP7 gene expression was highest in LC astrocytes relative to the other cell types, and that the MDD-associated reduction in BMP7 gene expression was limited to astrocytes. Rats exposed to chronic social defeat exhibited a similar reduction in BMP7 gene expression in the LC. BMP7 has unique developmental and trophic actions on catecholamine neurons and these findings suggest that reduced astrocyte support for pontine LC neurons may contribute to pathology of brain noradrenergic neurons in MDD.
authors: Department of Pharmacology, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. ordway@etsu.edu
authors: Gregory A
authors: GA
authors: Ordway
authors: Attila
authors: A
authors: Szebeni
authors: Michelle J
authors: MJ
authors: Chandley
authors: Craig A
authors: CA
authors: Stockmeier
authors: Lianbin
authors: L
authors: Xiang
authors: Samuel S
authors: SS
authors: Newton
authors: Gustavo
authors: G
authors: Turecki
authors: Michelle M
authors: MM
authors: Duffourc
authors: Meng-Yang
authors: MY
authors: Zhu
authors: Hobart
authors: H
authors: Zhu
authors: Katalin
authors: K
authors: Szebeni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D051381:Rats; D012189:Retrospective Studies; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult
chemical_list: D055419:Bone Morphogenetic Protein 7; D005904:Glial Fibrillary Acidic Protein; D014446:Tyrosine 3-Monooxygenase; D052006:Bone Morphogenetic Protein Receptors, Type II