ABSTRACT
Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities. The changes in microglial phagocytosis on a functional and transcriptional level were similar to those observed in a mouse model of Alzheimer's disease hinting to a related microglial phenotype in neurodegenerative and psychiatric disorders. Minocycline treatment of adult MIA offspring reverted completely the transcriptional, functional and behavioral deficits, highlighting the potential benefits of therapeutic targeting of microglia in psychiatric disorders.
Subject(s)
Adult Children/psychology , Anti-Bacterial Agents/pharmacology , Immune System Phenomena/drug effects , Microglia/drug effects , Minocycline/pharmacology , Synaptic Transmission/physiology , Transcriptome/genetics , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Animals , Anti-Bacterial Agents/administration & dosage , Behavior, Animal/drug effects , Disease Models, Animal , Female , Humans , Immune System Phenomena/physiology , Mice , Mice, Inbred C57BL/immunology , Microglia/metabolism , Minocycline/administration & dosage , Phagocytosis/immunology , Pregnancy , Schizophrenia/drug therapy , Schizophrenia/geneticsABSTRACT
The Reporter's Test requires the patient to verbally report to a hypothetical third person the actions the examiner is performing on an array of tokens, so as to enable him to replicate them. These performances correspond for the most part to the commands of the Token Test. The aim is to have the patient produce connected sequences of words, the choice and order of which is determined in advance and can be easily scored. The test was given to 70 normal controls, 60 aphasics (selected for absence of severe expressive impairment), 20 non-aphasic left brain-damaged patients and 20 right brain-damaged patients. Years of schooling, but not age, were found to significantly influence and the scores were consequently corrected. The inferior 5% limit of the 90% tolerance interval around the controls' mean was choosen as the cutting score discriminating a normal from a pathological performance. The hit rate of the Reporter's Test was 92% in the aphasic group. The percentage of non-aphasic left brain-damaged patients and right brain-damaged patients who scored below the cutting point and would, therefore, be erroneously classified as aphasic, was 10% and 15%, respectively. The screening power of the Reporter's Test was clearly superior to that of other expressive tests that were given to aphasic and non-aphasic brain-damaged patients. Besides the pass or fail score, a wheighted score, which takes into account the number of correct words chosen in the first four parts of the test, was used. Although somewhat inferior as a screening device, it presents the advantage of allowing a more graded evaluation of aphasics' performance.
