Perinatal exposure to infectious agents and toxins is linked to the pathogenesis 
of neuropsychiatric disorders, but the mechanisms by which environmental 
triggers interact with developing immune and neural elements to create 
neurodevelopmental disturbances are poorly understood. We describe a model for 
investigating disorders of central nervous system development based on neonatal 
rat infection with Borna disease virus, a neurotropic noncytolytic RNA virus. 
Infection results in abnormal righting reflexes, hyperactivity, inhibition of 
open-field exploration, and stereotypic behaviors. Architecture is markedly 
disrupted in hippocampus and cerebellum, with reduction in granule and Purkinje 
cell numbers. Neurons are lost predominantly by apoptosis, as supported by 
increased mRNA levels for pro-apoptotic products (Fas, caspase-1), decreased 
mRNA levels for the anti-apoptotic bcl-x, and in situ labeling of fragmented 
DNA. Although inflammatory infiltrates are observed transiently in frontal 
cortex, glial activation (microgliosis > astrocytosis) is prominent throughout 
the brain and persists for several weeks in concert with increased levels of 
proinflammatory cytokine mRNAs (interleukins 1alpha, 1beta, and 6 and tumor 
necrosis factor alpha) and progressive hippocampal and cerebellar damage. The 
resemblance of these functional and neuropathologic abnormalities to human 
neurodevelopmental disorders suggests the utility of this model for defining 
cellular, biochemical, histologic, and functional outcomes of interactions of 
environmental influences with the developing central nervous system.