Activation of the immune system during pregnancy can have varied effects on fetal development, and converging evidence highlights maternal immune activation as a risk factor for multiple neurological conditions. In this Review, Knuesel and colleagues discuss the involvement of maternal immune activation in schizophrenia, austim spectrum disorders, epilepsy and other disorders. The authors then discuss how preclinical data indicate a possible link between prenatal exposure to infection and susceptibility to neurodegenerative disease, and they go on to identify fertile ground for further translational research.

Maternal immune activation and abnormal brain development across CNS disorders.

Immunological aspects in the neurobiology of suicide : Elevated microglial density in schizophrenia and depression is associated with suicide

Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium.

Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study

Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disor- ders, which occur in childhood. They are charac- terized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunolog- ical, and neurological factors are thought to play a role in the development of ASD. Recently, increas- ing research has focused on the connections be- tween the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual's lifetime, with successful neurodevelop- ment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnor- mal or skewed T helper cell type 1 (TH1)/TH2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbal- ance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including hu- man leukocyte antigen (HLA)-DRB1 and comple- ment C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dys- function characteristic of ASD. This review will examine the status of the research linking the im- mune response with ASD. J. Leukoc. Biol. 80: 1-15; 2006.

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The immune response in autism: a new frontier for autism research

Glia play a major role in neuronal migration, synapse formation, and control of neurotransmission in the developing and mature nervous system. This study investigated whether chronic schizophrenia is associated with glial changes in 3 regions of the cerebral cortex: dorsolateral prefrontal cortex (Brodmann's area 9), the superior temporal gyrus (area 22), and the anterior cingulate gyrus (area 24). In a blind study, astroglia and microglia were identified immunocytochemically in frozen sections from postmortem schizophrenic and control brains. Astroglia and microglia were identified using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR) respectively. They were then quantified for each cortical layer. Significant differences were found in HLA-DR+ microglial numerical density in 2 of the areas. A 28% increase (p < 0.05) was found in area 9 in 8 schizophrenics (115 +/- 9 cells/mm2) compared with 10 controls (89 +/- 5 cells/mm2), when combining all cortical layers and both cerebral hemispheres. For area 22, there was a 57% increase (p < 0.01) in microglia in 7 schizophrenics (139 +/- 6 cells/mm2) compared with 10 controls (88 +/- 5 cells/mm2). In area 24 the same trend was evident, but the results did not reach significance. Microglial number was further analyzed for each cortical layer, which confirmed the overall pattern. For all areas, numerical density of astroglia showed no significant differences between schizophrenics and controls. Cortical thickness was measured in all areas and total neuronal numerical density was estimated for area 22. Again, no significant differences were found between schizophrenics and controls. This study demonstrates a specific increase in the numerical density of HLA-DR+ microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, which might be implicated in possible changes in cortical neuropil architecture in schizophrenia.

Katrina Radewicz

Papers

Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics.

Increase in microglia in frontal and temporal cortex of schizophrenics

A neuroanatomical study of glial cells in schizophrenia