Immune-defective mice show developmental brain anomalies that are similar to those seen in dyslexics and exhibit abnormal learning behaviors. Dyslexics and their families may have a greater incidence of some immune disorders. In the first period of the Program Project, we documented brain, behavioral and immunological abnormalities in strains of immune- defective mice and searched for causes of the brain abnormalities. We also developed a second model of induced minor developmental brain anomalies, which share many features of the spontaneous anomalies and offer experimental advantages. We carried out preliminary research that suggests a special role of the uterine environment for some immunological and behavioral characteristics. The purpose of the continuation research is to pursue lines of evidence that have been productive and convergent. One is the further study of minor developmental brain malformations. A detailed analysis of the onset and evolution of the spontaneous and induced brain abnormalities will be carried out in the Anatomy 1 Research Project, which will also look at the effect of timing and severity of the insult and the effect of neuroprotective substances on the resultant brain lesion. Changes in cellular and connectional architecture and behavior will be described in standard and manipulated lesions by the Anatomy 2 and Behavior research projects. Behavior research will also look at effects of early life experience and other ways of facilitating learning, including the use of drugs. The Embryo Transfer Research Project will assess the effects of changing the uterine and neonatal environments on anatomy, immunology, and behavior and at the effects of modulating autoimmunity in mothers. A Breeding Core will be established to insure uniform supply of difficult-to- obtain animals. A Neuroanatomy Core will screen brains arising in the research components for anomalies. A Data Registry and Processing Core will keep and analyze databases arising from the components of the Program Project. It is expected that the proposed work will contribute to the understanding of the onset, course, consequences, and causes of minor cortical malformations with an aim to improving prevention and treatment of learning disorders in children and adults.
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