Virus infections of the developing brain are a serious and common cause of pediatric neurological disease. Since the brain continues to develop after birth, central nervous system (CNS) injuries can be sustained following pre-, peri- and post-natal virus infections. HIV causes one of the most common virus-induced neurological diseases of children in the US. Notably, although clinical evidence of developmental neurological disease is a prominent finding in HIV infected children, the mechanisms of the virus-related neurological developmental injury are poorly understood. Studies of Borna disease virus (BDV)-infected neonatal Lewis rats have revealed important principles about the neuroanatomical and neurobehavioral effects on brain development of persistent virus infections of the brain. This animal model system is useful for the study the pathogenesis of developmental neurological diseases following perinatal HIV infection.
In Specific Aim 1, BDV-induced developmental damage to the rat cerebellum will be measured via quantitative measurements of cerebellar size and cortical development and cerebellar and hippocampal dentate gyrus neuron survival over time. In a mechanistic analysis, we will identify changes in important developmental gene mRNA expression in the cerebellum following perinatal virus infection.
Specific Aim 2 explores associated abnormalities in the development of sensorimotor, emotion, cognitive, and social behaviors and abnormalities in neurotransmitter concentrations in the infected brain as a function of time post virus infection. The results of these multidimensional neuroanatomical/ neurobehavioral pathogenesis studies will advance our knowledge of the effects of viruses on infant brain development, and of anatomical- behavioral pathology linkages following perinatal infection with a persistent RNA virus.
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