Expression of the axonal membrane glycoprotein M6a is regulated by chronic stress

• Published in: PloS one Vol. 4; no. 1; p. e3659
• Main Authors: Cooper, Ben, Fuchs, Eberhard, Flügge, Gabriele
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.01.2009; Public Library of Science (PLoS)
• Subjects: Alternative splicing; Animals; Axons; Axons - metabolism; Brain; Brain - metabolism; Brain research; Dendrites; Dendritic spines; Dentate gyrus; Dopamine; Down-Regulation; Gene Expression; Gene Expression Regulation; Glutamatergic transmission; Glycoproteins; Granule cells; Hippocampus; In Situ Hybridization; Information transfer; Kidney - metabolism; Laboratory animals; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membranes; Methyltransferases; Molecular Biology/mRNA Transport and Localization; Morphology; mRNA; N6-methyladenosine; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neurobiology; Neurons; Neurons - metabolism; Neuroscience/Neurobiology of Disease and Regeneration; Neuroscience/Neuronal and Glial Cell Biology; Neurosciences; Physiology; Prefrontal cortex; Protein Isoforms; Pyramidal cells; Rats; Rats, Sprague-Dawley; Restraint, Physical; RNA; RNA, Messenger - metabolism; Rodents; Stress; Stress, Physiological - physiology; Stresses; Topography; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003659

It has been repeatedly shown that chronic stress changes dendrites, spines and modulates expression of synaptic molecules. These effects all may impair information transfer between neurons. The present study shows that chronic stress also regulates expression of M6a, a glycoprotein which is localised in axonal membranes. We have previously demonstrated that M6a is a component of glutamatergic axons. The present data reveal that it is the splice variant M6a-Ib, not M6a-Ia, which is strongly expressed in the brain. Chronic stress in male rats (3 weeks daily restraint) has regional effects: quantitative in situ hybridization demonstrated that M6a-Ib mRNA in dentate gyrus granule neurons and in CA3 pyramidal neurons is downregulated, whereas M6a-Ib mRNA in the medial prefrontal cortex is upregulated by chronic stress. This is the first study showing that expression of an axonal membrane molecule is differentially affected by stress in a region-dependent manner. Therefore, one may speculate that diminished expression of the glycoprotein in the hippocampus leads to altered output in the corresponding cortical projection areas. Enhanced M6a-Ib expression in the medial prefrontal cortex (in areas prelimbic and infralimbic cortex) might be interpreted as a compensatory mechanism in response to changes in axonal projections from the hippocampus. Our findings provide evidence that in addition to alterations in dendrites and spines chronic stress also changes the integrity of axons and may thus impair information transfer even between distant brain regions.