Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression

Gregory A. Ordway, Attila Szebeni, Michelle J. Chandley, Craig A. Stockmeier, Lianbin Xiang, Samuel S. Newton, Gustavo Turecki, Michelle M. Duffourc, Meng Yang Zhu, Hobart Zhu, Katalin Szebeni

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)855-868
Number of pages14
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number7
DOIs
StatePublished - Aug 1 2012

Fingerprint

Bone Morphogenetic Protein 7
Locus Coeruleus
Major Depressive Disorder
Astrocytes
Brain Stem
Depression
Gene Expression
Adrenergic Neurons
Neurons
Brain
Pathology
Laser Capture Microdissection
Oligodendroglia
Transforming Growth Factors
Neuroprotective Agents
Amygdala
Prefrontal Cortex
Antidepressive Agents
Catecholamines
Neurotransmitter Agents

Keywords

  • Astrocyte
  • bone morphogenetic protein
  • glia
  • locud coeruleus
  • major depression
  • noradrenergic
  • suicide

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression. / Ordway, Gregory A.; Szebeni, Attila; Chandley, Michelle J.; Stockmeier, Craig A.; Xiang, Lianbin; Newton, Samuel S.; Turecki, Gustavo; Duffourc, Michelle M.; Zhu, Meng Yang; Zhu, Hobart; Szebeni, Katalin.

In: International Journal of Neuropsychopharmacology, Vol. 15, No. 7, 01.08.2012, p. 855-868.

Research output: Contribution to journalArticle

Ordway, GA, Szebeni, A, Chandley, MJ, Stockmeier, CA, Xiang, L, Newton, SS, Turecki, G, Duffourc, MM, Zhu, MY, Zhu, H & Szebeni, K 2012, 'Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression', International Journal of Neuropsychopharmacology, vol. 15, no. 7, pp. 855-868. https://doi.org/10.1017/S1461145711001350
Ordway, Gregory A. ; Szebeni, Attila ; Chandley, Michelle J. ; Stockmeier, Craig A. ; Xiang, Lianbin ; Newton, Samuel S. ; Turecki, Gustavo ; Duffourc, Michelle M. ; Zhu, Meng Yang ; Zhu, Hobart ; Szebeni, Katalin. / Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression. In: International Journal of Neuropsychopharmacology. 2012 ; Vol. 15, No. 7. pp. 855-868.
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