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.