In a second part of our study we used an antibody to the kainate receptor subunit GluR 5/6/7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex

In a second part of our study we used an antibody to the kainate receptor subunit GluR 5/6/7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex. correlation of spine loss with age at death. Our results support the concept of a neurodevelopmental defect in the neuropil affecting glutamatergic neurons in schizophrenia and may help to explain loss of cortical volume without loss of neurons. In a second part of our study we used an antibody to the kainate receptor subunit GluR 5/6/7 and showed a decrease in numerical density of presumed glutamatergic neurons in schizophrenic orbitofrontal cortex. Finally, as glia play a major role in the developing nervous system, we investigated whether schizophrenia was associated with glial changes in frontal and temporal cortex. Astroglia and microglia were identified in schizophrenic and control brains, using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR), respectively. Significant increases were found in microglial Rabbit polyclonal to baxprotein numerical density in schizophrenics compared with controls: 28% in frontal area 9 (115 cells mm?2 compared with 89), and a 57% increase in temporal area 22 (139 cells mm?2 compared with 88). For both areas, astroglia showed no significant differences between schizophrenics and controls. No significant differences were found in cortical thickness or total neuronal numerical density between the two groups. This specific increase in numerical density of microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, could be related to possible changes in cortical neuropil architecture as revealed by loss of dendritic spines. (Johnstone et al. 1976; Weinberger et al. 1979; Andreasen et al. 1982; Reveley et al. 1982; DeLisi et al. 1986; Pfefferbaum et al. 1988; Suddath et al. Ac-Lys-AMC 1989), and may be fully developed before the onset of illness (Frangou & Murray, 1996). Studies showed a decrease in volume of cerebral cortex but no change in that of subcortical white matter (Suddath et al. 1989; Zipursky et al. 1992; Harvey et al. 1993), suggesting that there is no loss of axons or probably of somata of cortical neurons (Selemon et al. 1995; Selemon & Goldman-Rakic, 1999), but there is a loss in neuronal processes, such Ac-Lys-AMC as axon terminals or dendritic branches or spines, in the cortical neuropil. More recent imaging studies have extended the original observations, showing that patients with schizophrenia have decreased grey matter in frontal, temporal and parietal cortices compared with controls (Honea et al. 2008). Furthermore, van Haren et al. (2008) observed that changes in brain volume throughout life were different between schizophrenics and controls. This was particularly evident in the Ac-Lys-AMC first 20 years or so of illness (before the age of 45), when grey matter loss and lateral ventricle increase were most marked in patients relative to controls. Patients also showed increase in third ventricle volume over time. Ac-Lys-AMC Poor outcome patients showed more brain tissue loss than good outcome patients. So, overall there seems to be loss of cerebral tissue, at least in the early stages of schizophrenia. But this may be of neuropil rather than of neuronal cell bodies. To investigate possible changes in neuropil, we carried out studies of dendritic spines (Garey et al. 1993, 1995, 1998), in the light of our evidence of the large changes they undergo during normal development (Michel Ac-Lys-AMC & Garey, 1984; Fig. 1) at a time when major changes are taking place in human cortical neuronal architecture (Mrzljak et al. 1992; Cao et al. 1996; Yan et al. 1996, 1997) and synaptogenesis (Huttenlocher, 1979, 1984; Huttenlocher & Dabholkar, 1997; Huttenlocher et al. 1982; Rakic et al..