H5N1 Influenza Virus Induces a Parkinsonian Pathology

The greatest threat for an influenza pandemic at this time is posed by the highly pathogenic H5N1 avian influenza virus. To date, 63% of the 436 known human cases of H5N1 infection have proven fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances and coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection. We show that this virus travels from the peripheral nervous system into the central nervous system (CNS) to higher levels of the neuroaxis, using C57BL/6J mice that are infected by the A/VN/1203/04 H5N1 virus (without adaptation). In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection. To determine if the pathology worsened with age, we examined: 1) substantia nigra pars compacta (SNpc) tyrosine hydroxylase positive dopaminergic neuron number and striatal dopamine and its metabolites contents through 90 days post infection (dpi), 2) examined the inflammatory effect of infection by quantitatively measuring the total number of resting and activated microglia in the SNpc and then examined the production of cytokines in regions of the brain infected by H5N1. We found that infection with H5N1 induces a reversible reduction of both the number of dopaminergic neurons in the SNpc and the amount of dopamine and its metabolites in the striatum. Examination of other indolamines demonstrated a significant and sustained reductionof serotonin in regions of the brain infected with H5N1. We also observed that areas of the brain infected with H5N1 expressed altered levels of pro-inflammatory cytokines, chemokines and growth factors. We examined if H5N1 priming potentiates paraquat (PQ) induced neurotoxicity in the basal ganglia. We found that H5N1 priming did not increase the sensitivity of C57BL/6J mice to intraperitoneal (ip) administration of paraquat. Rather, H5N1 priming protects the dopaminergic neurons from PQ-induced neurodegeneration and diminishes immune response produced by PQ in the CNS

Viral parkinsonism

AbstractParkinson's disease is a debilitating neurological disorder that affects 1–2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses

Effects of 2-Week Exercise Training in Hypobaric Hypoxic Conditions on Exercise Performance and Immune Function in Korean National Cycling Athletes with Disabilities: A Case Report

We aimed to evaluate the effects of a 2-week exercise training program in hypobaric hypoxic conditions on exercise performance and immune function in Korean national cycling athletes with disabilities. Six Korean national cycling athletes with disabilities participated in exercise training consisting of continuous aerobic exercise and anaerobic interval exercise in hypobaric hypoxic conditions. The exercise training frequency was 60 min (5 days per week for 2 weeks). Before and after the exercise training, exercise performance and immune function were measured in all athletes. Regarding the exercise performance parameters, the 3-km time trial significantly decreased and blood lactate levels after the 3-km time trial test significantly increased by exercise training in hypobaric hypoxic conditions. Regarding the oxygen-transporting capacity, significant differences were not observed. Regarding immune function, the number of leukocytes and natural killer cells significantly decreased and that of eosinophils, B cells, and T cells significantly increased. These results indicated that our 2-week hypoxic training showed the potential to improve exercise performance in Korean national disabled athletes. However, the effects of our hypoxic training method on immune function remained unclear.</jats:p