Perspective on Sleep and Aging

There is a strong body of data directly interrelating sleep problems with mood disorders. There is a growing data base directly associating sleep disorders with attention and memory problems. Motor disorders, especially involving the dopaminergic system, may produce sleep problems, including a possible association between disordered sleep and nocturnal falls. Sleep disorders may be causal conditions for metabolic diseases and increased risk for morbidity and mortality. Sleep and health are directly interrelated. To further probe these issues, especially as related to the aging process, investigators need to utilize tools and concepts from genomics and epigenetics, proteomics, metabolomics, any future …omics, molecular neuroimaging, and cognitive neuroscience

IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS : I. CYCLOPHOSPHAMIDE-MEDIATED INDUCTION OF THE VIRUS-CARRIER STATE IN ADULT MICE

A single dose of 150 mg/g of cyclophosphamide (CY), given 3 days after intracerebral (i.c.) inoculation of lymphocytic choriomeningitis (LCM) virus, protected over 90% of adult BALB/c mice against acutely fatal choriomeningitis. Surviving mice became persistently infected carriers, with high virus titers in blood and brain. Immunofluorescent examination of the brain showed that in CY-induced carriers infection was initially confined to the choroid plexus, ependyma, and leptomeninges, but over the next 30 days gradually spread to the neural parenchyma, most notably to the molecular layer of the cerebellum. By contrast, LCM virus-carrier mice produced by neonatal virus injection and examined as adults, showed a much less marked infection of choroid plexus and much more widespread infection of parenchyma, with a different distribution among brain nuclei, including heavy infection of the Purkinje cells of the cerebellum

Diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses

This chapter highlights the neurologic sequelae of viruses from two major groups of arenaviruses, the Lassa-lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Fundamental features of these viruses are reviewed, including the rich history of their discovery and the large influence that the study of arenaviruses has had on the disciplines of virology and immunology more generally. Virus morphology, viral genome organization, individual viral protein functions, and small-animal models of disease are also discussed. The epidemiology, natural history, and laboratory evaluation of the arenaviruses that cause human illness are presented. In particular, the neurologic complications of lymphocytic choriomeningitis virus in immunocompetent, pregnant, and solid-organ transplant patients are highlighted. The neurologic sequelae of the arenaviruses that cause hemorrhagic fever (i.e., Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Venezuelan hemorrhagic fever) are also presented. Lastly, potential treatment and vaccine strategies of these diseases are reviewed. © 2014 Elsevier B.V

Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV