engleski

D2, D3 and D4 dopamine receptor expression in the prefrontal cortex of normal and schizophrenic brains

The knowledge of the dopamine system is enormously important for understanding the human behavior, as well as for the pathophysiology of many neurological and psychiatric diseases. Functional disturbance of the midbrain dopamine trajectories to the prefrontal cortex (PFC) have been commonly implicated to psychiatric disorders like schizophrenia, autism, depression and drug abuse. So far, the majority of studies addressing the localization of dopamine receptors (DR) in the human brain used crude scintigraphic approach of ligand binding, while the precise anatomical localization of dopamine receptors in the PFC, particularly of the D2 group, has been largely neglected. Human brain tissue was taken during autopsy from 4 schizophrenic patients (age range: 51-59 years) and 3 age-matched controls (48-56 years) with no history of neurological and psychiatric disorders. Tissue specimens from the right orbitomedial PFC (BA11/12) of each brain were analyzed. The blocks were fixed in 4% paraformaldehyde, dehydrated, paraffin-embedded and cut in 12-micron thick sections. For immunocytochemistry the sections were stained using novel anti-DRD2, DRD3 and DRD4 antibodies. The specificity of the antibodies used was previously characterized by Wolstencroft, Šimić et al. in 2007. In schizophrenic brains, we found strong DRD2 immunoreactivity in pyramidal neurons of layer III and moderate in layer V pyramidal cells. Inversely, the expression of DRD4 was stronger in layer V pyramidal neurons. The expression of DRD3 was generally weaker than for DRD2 and DRD4. Contrary to normal controls, a significant number of DRD2-immunoreactive reactive astroglial cells, predominantly in the subcortical white matter, were found in all four schizophrenic brains. This finding represented the major difference in the dopamine receptors expression between normal and schizophrenic brains. Pyramidal cell expression of DR of the D2 group confirms that the activity of the prefrontal neuronal circuits is strongly modulated by dopamine transmission. The pronounced expression of the DRD2 receptors in reactive astrocytes of all four schizophrenic brains analyzed suggests its possible importance for the pathogenesis of schizophrenia.

confocal microscopy; dopamine receptors; expression pattern; glia; immunocytochemistry; immunofluorescence; prefrontal cortex; pyramidal neurons; schizophrenia

This poster presentation was also presented at the symposium "Neurogenomics and neuroimaging of developmental disrders" held from 30 April - 5 May 2009. in Dubrovnik