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

Autor: Hobart Zhu, Gustavo Turecki, Katalin Szebeni, Meng-Yang Zhu, Michelle J. Chandley, Samuel S. Newton, Attila Szebeni, Lianbin Xiang, Gregory A. Ordway, Michelle M. Duffourc, Craig A. Stockmeier
Rok vydání: 2011
Předmět:
Adult
Male
medicine.medical_specialty
Adolescent
Tyrosine 3-Monooxygenase
Bone Morphogenetic Protein 7
Bone Morphogenetic Protein Receptors
Type II
Young Adult
Norepinephrine
Noradrenergic neuron differentiation
Internal medicine
Glial Fibrillary Acidic Protein
Gene expression
medicine
Animals
Humans
Pharmacology (medical)
Aged
Retrospective Studies
Aged
80 and over
Pharmacology
Depressive Disorder
Major
biology
Brain
Middle Aged
Rats
Bone morphogenetic protein 7
Disease Models
Animal
Psychiatry and Mental health
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Astrocytes
Case-Control Studies
embryonic structures
biology.protein
Locus coeruleus
Female
Locus Coeruleus
Catecholaminergic cell groups
Psychology
Microdissection
Neuroscience
Astrocyte
medicine.drug
Neurotrophin
Zdroj: The International Journal of Neuropsychopharmacology. 15:855-868
ISSN: 1469-5111
1461-1457
DOI: 10.1017/s1461145711001350
Popis: 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.
Databáze: OpenAIRE
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