Excessive expression of synaptojanin in brains with Down syndrome

We investigated the expression of synaptojanin, which has been mapped on 21q22.2 on human chromosome, in the cerebral cortex of patients with Down syndrome (DS), using immunohistochemistry and immunoblotting. Synaptojanin expression was observed in Cajal-Retzius cells, cortical plate neurons, subplate neurons, intermediate neurons, germinal matrix cells and the ventricular neuroepithelium of the fetal cerebrum in both controls and DS. After birth, synaptojanin immunoreactivity was mainly observed in cytoplasm of cortical neurons and neurophils. These expressions of synaptojanin suggest a broader role in not only synaptic vesicle recycling, but also the regulation of neuronal migration and synaptogenesis in the fetal period. In comparison with controls, DS brains clearly showed higher immunoreactivity of synaptojanin in every structure, and most of the large neurons showed immunoreactivity. Western blotting with synaptojanin confirmed the increased expression in DS brains. Although the reason for excessive expression of synaptojanin in DS brains is obscured, one possibility can be explained on the basis of a gene dosage effect. As another possibility, on the assumption that synaptojanin modulates synaptic transmission and plays roles in clathrin-mediated synaptic vesicle endocytosis and signaling, the excessive expression of synaptojanin may be involved in compensatory mechanisms occurring in developing DS brains, such as neuronal loss, atrophic basilar dendrites, decreased spines and abnormal synaptic density and length.