Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair

^a Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, 90024, USA

^b Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, 90024, USA

^c Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90024, USA

Abstract

Mice deficient in classical major histocompatibility complex class I (MHCI) have aberrations in neurodevelopment. The consequences of upregulated neuronal MHCI expression have not been examined. We found that transgenic C57Bl/6 mice that are engineered to express higher levels of self-D^b on their CNS neurons have alterations in their hippocampal morphology and retinogeniculate projections, as well as impaired neurorepair responses. Thus, enhanced neuronal classical MHCI expression can lead to aberrations in neural circuitry and neurorepair. These findings complement a growing body of knowledge concerning the neurobiological activities of MHCI and may have potential clinical relevance.