High molecular weight microtubule-associated protein 2 over-expression in neuronal migration disorders caused by N-methyl-D-aspartate receptor activation in hamsters

To evaluate the neuronal cytoarchitectural changes in neuronal migration disorders, the immunohistochemical expression of microtubule-associated proteins (MAPs) was analyzed using the experimental model induced by ibotenate in newborn hamsters. The cortical lesions observed after intracerebral ibotenate injections strongly resembled the following neuronal migration disorders: (1) microgyria; (2) focal subcortical heterotopia; (3) focal subependymal heterotopia; and (4) leptomeningeal glioneuronal heterotopia. Microgyria and leptomeningeal glioneuronal heterotopia had MAP2 (HM-2: high and low-molecular-weight forms of MAP2) immunoreactive dendritic processes or neuronal elements. The high molecular weight isoform of MAP2 (AP-20), which is more characteristic of mature neurons, showed enhanced expression in neurons of focal subcortical or subependymal heterotopia, although MAP1B (AA6: early form of MAP) immunoreactive elements were not detected in these heterotopic areas. We conclude that high molecular weight isoform of MAP2 is closely associated with cytoarchitectural repair and remodeling of neuronal processes, resulting in neuronal heterotopia after NMDA receptor activation.