Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization
- 537 Downloads
Immunological alterations have been demonstrated in peripheral blood and cerebrospinal fluid of patients with schizophrenia, while previous postmortem studies have provided an inconsistent picture as to the role of microglia in the context of schizophrenia. Microglial activation is a sensitive indicator of changes in the CNS microenvironment, such as inflammatory and neurodegenerative processes. The aim of the present postmortem study was to examine HLA class II (HLA-DR) expression on microglia in brain regions which are particularly relevant for schizophrenia, with regard to hemispheric lateralization. Dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus and mediodorsal thalamus (MD) were studied in 16 cases with schizophrenia and 16 control subjects. Immunostaining was found in all brain regions and was not restricted to macrophage-like ameboid cells, but also appeared in ramified cells. Region-specific HLA-DR-positive cell density was not significantly different between cases with schizophrenia and controls. However, ameboid microglial cells were lateralized towards the right hemisphere in healthy subjects but not in the schizophrenia group (P=0.01). Postmortem interval correlated with ramified cell numbers in ACC/DLPFC (P=0.01/0.04) and ameboid cell density in hippocampus (P=0.03). Age, gender, duration of disease, medication dosage, storage delay and whole brain volume had no effect. Single case analysis revealed highly elevated microglial cell numbers in ACC and MD of two schizophrenic patients who had committed suicide during acute psychosis. In conclusion, the present data suggest the absence of microgliosis but decreased cerebral lateralization of ameboid microglia in schizophrenia.
KeywordsSchizophrenia Microglia HLA-DR Lateralization
The Saxony-Anhalt Ministry of Research (XN3594O/0405M, Signaltransduzierende Netzwerke N2), German Ministry of Research (BMBF-NBL3 01ZZ0107, BrainNet) and Stanley Foundation supported the present study. We thank Dr. Alan Richardson-Klavehn for checking the English language of the manuscript. Gabriele Meyer-Lotz and Sieglinde Funke provided excellent technical assistance.
- 7.Damadzic R, Bigelow LB, Krimer LS, Goldenson DA, Saunders RC, Kleinman JE, Herman MM (2001) A quantitative immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia, bipolar disorder and major depression: absence of significant astrocytosis. Brain Res Bull 55:611–618PubMedCrossRefGoogle Scholar
- 20.Hirsch S (2004) Clinical changes measured by [11C](R)-PK11195 PET in patients with psychosis and cognitive decline are associated with impaired event related potential mismatch negativity (abstract from the 12th biennial winter workshop on schizophrenia, Davos, Switzerland). Schizophr Res 67:103Google Scholar
- 26.Mai JK, Assheuer J, Paxinos G (2003) Atlas of the human brain. Academic, San DiegoGoogle Scholar
- 29.Mittelbronn M, Dietz K, Schluesener HJ, Meyermann R (2001) Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude. Acta Neuropathol (Berl) 101:249–255Google Scholar
- 46.van Berckel B, Boellaard R, Caspers E, Cahn W, Lammertsma A, Kahn R (2005) Microglia activation in schizophrenia: an (R)-[11C]-PK11195 positron emission tomography study (abstract from the 2005 international congress on schizophrenia research, Savannah, Georgia). Schizophr Bull 31:448Google Scholar
- 48.Wagner-Jauregg J (1887) Über die Einwirkung fieberhafter Erkrankungen auf Psychosen. Allg Z Psychiatr 27:93–131Google Scholar