Transient focal cerebral ischemia differentially decreases Homer1a and 1b/c contents in the postsynaptic density

Homer is a scaffold protein in the postsynaptic density (PSD) and binds to the intracellular tail of group I metabotropic glutamate receptors (mGluRs). Although Homer contributes to the regulation of physiological function in synapses, the role of Homer proteins under pathophysiological conditions, such as cerebral ischemia, is still not fully clear. In the present study, we sought to determine whether transient focal cerebral ischemia would affect the level of Homer1 in the isolated-PSD fraction from rats. We showed that Homer1a (short form) and Homer1b/c (long form) as well as group I mGluR were localized in the cortical PSD. Cerebral ischemia decreased the content of Homer1a, which is a dominant-negative inhibitor of the long form of Homer proteins, in the PSD at 4 h of reperfusion without changing the level of Homer1a in cortical homogenates. On the other hand, the levels of Homer1b/c in the both PSD and homogenates were decreased at 24 h of reperfusion. These results suggest that these decreases in the level of Homer1 proteins after cerebral ischemia may contribute to the disturbance of synaptic function and subsequent development of cerebral ischemia.

► Homer1a and Homer1b/c were present in a higher concentration in the PSD fraction.
► Cerebral ischemia decreased the Homer1a levels in the PSD at 4 h of reperfusion.
► The levels of Homer1b/c in the PSD were decreased at 24 h of reperfusion.